PPG3 Rdedition

PARKLAND
POCKET GUIDE TO
HIV CARE
3rd EDITION
NAIEL N. NASSAR, M.D.

PHILIP KEISER, M.D.
CLARK R. GREGG, M.D.
PARKLAND
POCKET GUIDE
TO HIV CARE
3RD EDITION
NAIEL N. NASSAR, M.D., F.A.C.P.

Assistant Professor
Internal Medicine
UT Southwestern Medical Center
Dallas, TX
PHILIP KEISER, M.D.
Associate Professor of Medicine

Division of Infectious Diseases
University of Texas Southwestern Medical Center at Dallas
Director, HIV Clinic, Parkland Memorial Hospital
Principal Investigator, TX/OK AIDS Education & Training Center
Dallas, Texas
CLARK R. GREGG, M.D.
Professor of Medicine
University of Texas Southwestern Medical Center at Dallas
Chief, Medical Services
Veterans Affairs North Texas Health Care System
Dallas, TX
Texas / Oklahoma
AIDS Education & Training Center
Parkland Health & Hospital System
Dallas, Texas
November 2004
Supported by a grant from Health Resources & Services Administration
To send your comments or to request additional or future copies

of this publication, please do so in writing, addressed to:
Texas/Oklahoma AIDS Education & Training Center
4811 Harry Hines Blvd.
Dallas, Texas 75235
You can reach us at 1-877-ASK-AETC
or email us at tx.ok.aetc@parknet.pmh.org
www.aidseducation.org
CONTRIBUTORS
Jamshid Amanzadeh, M.D.
Nephrology Section
Assistant Professor
Internal Medicine
Dallas, TX
Laura Armas, MD
Internal Medicine
Clinical Director, TX/OK AIDS Education & Training Center
Dallas, TX
Ruth Berggren, M.D.
Assistant Professor
Section of Infectious Diseases
Tulane University Medical Center
New Orleans, LA
Richard M. Dasheiff, M.D.
Associate Professor, Neurology
Dallas, TX
Clark R. Gregg, M.D.
Professor of Medicine
Chief, Medical Services
University of Texas Southwestern Medical Center
Dallas, TX
William Vandier Harford, M.D.
Professor
Internal Medicine Digestive and Liver Diseases
Dallas,TX
CONTRIBUTORS
Shahbaz M. Hasan, MD
Associate Professor
Internal Medicine
Dallas, TX
Salahuddin Kazi, M.B.B.S.
Associate Professor
Internal Medicine
Dallas, TX
Philip Keiser M.D.
Associate Professor
Internal Medicine
Principal Investigator, Texas/Oklahoma
AIDS Education & Training Center (TX/OK
Asra Kermani, M.D.
Assistant Professor
Internal Medicine
Dallas, TX
Stanley Lewis, M.D.
Assistant Professor of Medicine
Division of General Internal Medicine
UT Health Science Center
Houston, TX
James P. Luby M.D.
Professor
Internal Medicine
Dallas, TX
CONTRIBUTORS
Linda J. Machado, M.D.
Assistant Professor
Internal Medicine
University of Oklahoma Health Science Center
Faculty, TX/OK AIDS Education & Training Center
David M. Margolis, M.D.
Associate Professor
Internal Medicine
Dallas, TX
Naiel Nassar, M.D.
Assistant Professor
Internal Medicine
Dallas, TX
Sanjay Revankar, M.D.
Assistant Professor
Internal Medicine
Dallas, TX
Zishan Samiuddin, M.D.
Professor, Psychiatry
Baylor College of Medicine
Houston, TX
Paul M. Southern Jr., M.D., DTM&H
Professor
Pathology and Internal Medicine
Dallas, TX
Johnny Stephens, PharmD
Assistant Professor
The University of Oklahoma
College of Pharmacy Tulsa Campus
Tulsa, OK
6
CONTRIBUTORS
Paolo Troia-Cancio, M.D.
Assistant Clinical Professor
Internal Medicine
UC Davis Medical Center
Sacramento, CA
Fehmida Visnegrawala, M.B.B.S.
Assistant Professor
Internal Medicine
Baylor College of Medicine
Houston, TX
Paschal Wilson, M.D.
Assistant Professor
Internal Medicine
Dallas, TX
Laura Wintereld, M.D.
Internal Medicine
Parkland Health & Hospital System
Dallas, TX
Special thanks to the following staff & volunteers for their
clerical assistance & support:
Michelle Dunn
Priyanka Lalwani
Debbie Watts
Chejuana Willis
EDITORS COMMENTS
The care of the HIV infected patient has rapidly evolved since this
syndrome was rst identied. Currently there are over 20 antiretroviral
agents licensed by the Food and Drug Administration. Remarkable
changes in the course of HIV infection have been wrought by these
therapies. AIDS deaths have decreased dramatically in the United
States. Over 75% of the individuals diagnosed with AIDS in 2000 are
still alive, primarily because of the availability of effective anti-retroviral
agents. HIV, in the developed world, has entered a new era, where
this infection can truly be considered a chronic disease. Despite these
successes, anti-retroviral therapy is complicated by short term and
long term toxicities which limit its effectiveness. Clinicians are faced
with the daunting task of individualizing therapy, so that each patient
may benet from these drugs.
The Parkland Health and Hospital System has been treating people
with HIV since the onset of the epidemic. This effort has evolved
over the last ten years and the Parkland HIV/AIDS clinic is now a
major research and trains health care workers in the treatment of
HIV. Currently, the Parkland system and its afliated institutions, the
University of Texas Southwestern Medical Center at Dallas and the
Dallas Veterans Affairs Medical Center actively follow approximately
4500 HIV infected people.
This book represents our cumulative experience in treating HIV
infected patients. It is intended to be a guide to the treatment of the
common manifestations of HIV and its related complications. It is not a
comprehensive textbook. We have made every effort to provide stateof-the-art information in the text. Where there is no clear consensus on
the treatment of a particular illness, we have given our best opinion,
based on the large number of patients we have seen over the years.
Since HIV knowledge is rapidly evolving, readers are urged to review
information about this disease and medications mentioned.
We hope that you nd the Parkland Guide useful in your care of
persons with HIV.
TABLE OF CONTENTS
EPIDEMIOLOGY OF HIV INFECTIONS & AIDS .................................... 11
HIV TRANSMISSION, INCLUDING HIV-2............................................15
HIV TESTING ..............................................................................21
INITIAL WORK-UP OF HIV ..............................................................25
ANTIRETROVIRAL THERAPY ............................................................31
RESISTANCE TESTING ...................................................................45
MANAGEMENT OF PERSONS EXPOSED TO HIV ..................................51
CLINICAL MANIFESTATIONS OF HIV INFECTION
DERMATOLOGICAL COMPLICATIONS .............................................55
PULMONARY COMPLICATIONS ....................................................65
GASTROINTESTINAL COMPLICATIONS ...........................................79
NEUROLOGICAL COMPLICATIONS ................................................89
ENDOCRINOLOGIC & METABOLIC COMPLICATIONS .......................109
RENAL DISORDERS................................................................ 115
RHEUMATOLOGIC COMPLICATIONS ............................................121
MALIGNANCY & HEMATOLOGIC COMPLICATIONS ..........................125
MENTAL HEALTH DISORDERS ..................................................139
PAIN MANAGEMENT ...............................................................147
WOMEN AND HIV/AIDS ........................................................157
COMMON CO-INFECTIONS IN HIV
CYTOMEGALOVIRUS ...............................................................161
DISSEMINATED MYCOBACTERIUM AVIUM COMPLEX (DMAC) ........167
FUNGAL INFECTIONS ..............................................................171
VIRAL HEPATITIS ...................................................................177
SEXUALLY TRANSMITTED DISEASES ..........................................181
THE HIV-INFECTED TRAVELER.................................................189
APPENDIX I: THERAPY FOR FREQUENT INFECTIOUS DISEASES
IN HIV PATIENTS ...................................................195
APPENDIX II: HIV RELATED DRUGS, INDICATIONS, DOSAGES
AND MOST COMMON SIDE EFFECTS .........................213
APPENDIX III: DISCONTINUATION OF OPPORTUNISTIC INFECTION
PROPHYLAXIS/MAINTENANCE AFTER IMMUNE
RECONSTITUTION ...................................................244
INDEX.......................................................................................244
9
10
EPIDEMIOLOGY OF HIV INFECTION & AIDS

LINDA MACHADO, MD
11

In the United States through 2002:
199,759 cumulative HIV infections were reported
859,000 cumulative AIDS diagnoses were reported
487,725 (57%) of those diagnosed with AIDS had died
In 2002
Non-Hispanic blacks accounted for 54% of reported AIDS cases
Hispanics accounted for 13% of reported AIDS cases
Global Summary of the HIV/AIDS Epidemic, December 2002
People newly identied
with HIV in 2002
Total
Adults
Women
Children < 15 yrs
5 million
4.2 million
2 million
800,000
Number of people living

with HIV/AIDS
Total
Adults
Women
Children < 15 yrs
42 million
38.6 million
19.2 million
3.2 million
AIDS deaths in 2002
Total
Adults
Women
Children < 15 yrs
3.1 million
2.5 million
1.2 million
610,000
United States Summary of the AIDS Epidemic 1981-2001

Cases
Total
Adults and adolescents
Children <13 yrs
816,149
807,075
9,074
Deaths
Total
Adults and adolescents
Children <13 yrs
467,910
462,653
5,257
Exposure Categories for AIDS Cases Reported in 2001: United States

Men Who have Sex With Men (MSM)
40%
Injection Drug Use (IDU)
26%
MSM & IDU

Heterosexual
Other/not identied
12
5%
28%
2%

CDC 1993 Revised Classication System For Infection and
Expanded Surveillance Case Denition for AIDS
Among Adolescents (13 years) and Adults
CD4
Category
Denition
CD4
Count/L
CD4%
Consists of one or more of the following:

Acute (primary) HIV infection
Asymptomatic HIV infection
Persistent generalized
lymphadenopathy
500
29
Consists of one or more of the following:

Acute (primary) HIV infection
Asymptomatic HIV infection
Persistent generalized
lymphadenopathy
200-499
14-28
Includes the conditions listed in the AIDS

surveillance case denition. Once a
Category C Condition has occurred,
the person so classied will remain in
Category C.
200
14
Conditions included in the 1993 AIDS surveillance

case denition
Candidiasis of bronchi, trachea, or lungs

Candidiasis, esophageal
Cervical cancer, invasive
Coccidioidomycosis, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary
Cryptosporidiosis, chronic intestinal (>1 month)
Cytomegalovirus disease, other than liver, spleen, or lymph
nodes
Cytomegalovirus, retinitis
Encephalopathy, HIV related
Herpes simplex: chronic ulcer(s) (>1 month duration), bronchitis,
pneumonitis, or esophagitis
Histoplasmosis, disseminated or extrapulmonary
Isosporiasis, chronic intestinal (>1 month)
Kaposis sarcoma
Lymphoma, Burkitts, immunoblastic, or primary of brain
13

Mycobacterium avium complex or Mycobacterium kansasii,
disseminated or extrapulmonary
Mycobacterium tuberculosis, any site
Mycobacterium, other species or unidentied species,
disseminated or extrapulmonary
Penicillium marnefeii infection, disseminated
Pneumocystis jerovici pneumonia (previously Pneumocystis
carinii pneumonia)
Pneumonia, recurrent
Progressive multifocal leukoencephalopathy
Salmonella septicemia, recurrent
Toxoplasmosis of the brain
Wasting syndrome due to HIV
14
HIV TRANSMISSION, INCLUDING HIV-2

FEHMIDA VISNEGRAWALA, MD
15

Sexual Transmission:
80-90% of HIV-1 and 2 transmission occurs via sexual exposure.
In developed countries homosexual contact among men has
been primary mode of transmission, however in most of the
developing world unprotected heterosexual contact with multiple
sexual partners is most common.
In general, different sexual practices have different risks of
transmission, with anal> vaginal>oral receptive intercourse. The
risk of HIV transmission among lesbians is minimal.
Risk of HIV transmission with unprotected vaginal intercourse in
sero discordant couples is highest during the acute stage of HIV
infection, 8/1000 coital acts, decreasing to 1/1000 during chronic
infection and 4/1000 in advanced disease. Thus people with
primary HIV infection cause disproportionately high number of
new infections.
There is selective transmission of CCR5 tropic virus in mucosal
transmission.
Overall there is good correlation in the level of plasma
viremia and detection of HIV in both male and female genital
tract. However, up to one third of women and <5% of men
had detectable genital tract HIV RNA with undetectable
plasma viremia, suggesting local replication of virus. This
has implications for resistance to ARV therapy due to
compartmentalization.
Level of plasma viremia, presence of other ulcerative and nonulcerative STDs, bacterial vaginosis, lack of male circumcision,
cervical ectopy, exogenous hormonal treatment, traumatic
intercourse, sex during menses, and in developing countries,
selenium and vitamin A deciencies, are associated with an
increased risk of sexual transmission. Treatment of genital copathogens has been associated with decreased HIV shedding,
perhaps decreasing transmission.
Data on gender differences in risk of acquiring HIV have not been
consistent (i.e., higher in male to female) and are related more to
level of viremia and presence of ulcerative STD.
Even though not 100 % effective, consistent and correct use of
condoms can substantially decrease risk of sexual transmission
of HIV and other STDs. Because transmission of resistant
HIV and superinfection with a different HIV strain has been
documented, it is important to encourage use of condoms.
There is increasing prevalence of drug resistant HIV
16

transmission, due to non-adherence to therapy and complacency
in use of safer sex practices.
Among individuals infected primarily with drug resistant HIV,
resistance mutations persist, thus decreasing the response
to anti-retroviral therapy. This is in contrast to acquired drug
resistance, where there is rapid reversion to wild type HIV upon
removal of drug pressure.
Parenteral Transmission:
Infected blood, blood products, or clotting factor concentrates
(prior to 1985) have transmitted HIV to recipients of transfusions,
IDUs exposed to contaminated needles/syringes, persons
exposed to contaminated blood via accidental exposure (e.g.,
health care workers) and tissue transplant recipients.
Since March 1985 all US blood donations are screened for
HIV-1 and since June 1992 for HIV-2. Risk of acquiring HIV
through transfusion of blood donated in the window before the
development of antibody in acute infection is estimated to be
1: 450,000 to 1: 660,000 units. Since August of 1995, FDA
recommends that all donated plasma and blood be screened for
p24 antigen to further reduce risk of HIV transmission.
From the time of mucosal/parenteral exposure to the
establishment of HIV infection, there is a window of 24-48 hours
in which the infection might be abolished using anti-retroviral
therapy. This is basis for post-exposure prophylaxis for sexual,
perinatal and accidental exposure to HIV.
Perinatal Transmission:
Risk of perinatal transmission without antiretroviral therapy is 1640%.
May occur in utero, during delivery most common, or breastfeeding.
Maternal risk factors for transmission: high level of viremia,
low CD4 count, genital ulcerative disease, chorioamnionitis,
prolonged rupture of membranes, pre-term delivery.
Passively acquired maternal antibodies persist 12-18 months,
thus making PCR and viral culture the only specic methods for
diagnosing HIV infection in infants.
17

Transmission in Health Care Setting:
Risk of HIV transmission via percutaneous sharps exposure
estimated at at 0.3% per exposure, and risk with mucocutaneous
exposure even lower.
Risk factors:
a) type of injury: percutaneous vs. mucous, hollow bore needle,
extent of injury (deep penetrating)
b) type of exposure: blood, blood tinged vs. other body uids, and
large amount or prolonged exposure, temperature, pH, age
and dryness of the uid
c) the amount HIV exposure: viral load in the uid.
Health Care workers (HCW) must always follow standard blood
and body uid precautions.
Precautions for care givers of HIV patients to decrease their risk
of transmission
Wear gloves when there is potential contact with urine, feces or
vomitus.
Cover their cuts, sores and abrasions. Do not share razors or
toothbrushes.
Wash exposed body part immediately with soap and water.
Dispose of needles and sharp instruments promptly in punctureproof container
Infection with HIV-2
HIV-2 infection rst discovered in Senegal (West Africa), and is
endemic in that region. Dual infection and superinfection with
HIV-1 and 2 have occurred.
HIV-1 at least 3 times more infectious per sexual act as HIV-2.
HIV-2 also less transmissible perinatally. Differences in perinatal
transmission may be related to lower level HIV viremia and less
advanced disease in HIV-2 infected mothers.
About 80% of HIV-2 patients will also test positively with HIV-1
ELISA, and western blots weakly cross reactive (indeterminate).
An HIV-2/HIV-1 combination ELISA and HIV-2 specic ELISA
commercially available. HIV-2 positive ELISA should be
conrmed with a western blot. Negative HIV-1 ELISA does not
rule out an HIV-2 infection .
Rate of progression to CDC stage IV is 3-4 times faster with HIV1 than with HIV-2, and rate to overt AIDS is 12-14 times faster.
HIV-2 patients thus likely to have much longer asymptomatic
period. Perinatally acquired HIV-2 infection may not be
recognized until puberty.
18

HIV-2 can mimic HIV-1 but acute retroviral syndrome has not
been well described, perhaps due to ascertainment bias.
Regimens for antiretroviral therapy and prophylaxis are similar for
HIV-1 and HIV-2 except that NNRTIs are inactive vs HIV-2.
Comparison of HIV 1 & HIV 2
HIV-1
HIV-2
Risk of Transmission per coital act
+++
Acute Retroviral Syndrome
+++
HIV Disease Progression
++++
CD4 Decline
++++
Susceptibility to NNRTIs
++++
19
20
HIV TESTING
PHILIP KEISER, MD
21
HIV TESTING
HIV testing has 3 components; pre-test risk counseling, HIV
testing and post-test counseling.
Pre-test counseling assesses risk for HIV infection and explains
testing procedure, including the meaning of preliminary and
conrmatory results.
Post-test counseling occurs after all results are completed. Those
with negative tests should be counseled on risk reduction. Those
with positive tests should be referred for HIV care and prevention
education.
Preliminary testing
ELISA Testing
The gold standard for preliminary HIV testing.
Detects serum antibodies to HIV.
Reactive ELISA sensitivity and specicity typically 99% is
repeated on the same sample. If ELISA reactive, a conrmatory
test is done on the same sample.
False-positive tests occur in multiparous women, recent
recipients of inuenza or HBV vaccines or multiple transfusions,
hematologic malignancies, autoimmune disorders, multiple
myeloma, primary biliary cirrhosis, or alcoholic hepatitis.
False negative ELISA may occur very early or late in the course
of HIV disease when antibody production is low.
Oraquick
Rapid HIV testing; with preliminary results within 20 minutes.
Requires only minimal blood from a nger stick.
Can be performed by ofce personnel; does not require trained
medical technologist
Counseling procedure must be altered to provide risk
assessment and risk reduction in one visit.
Positive test requires a conrmatory test such as a western blot.
Positive test results must be given as only preliminary.
Conrmatory test should be drawn, and patient should be reappointed for results and post-test counseling.
22
HIV TESTING
CONFIRMATORY TESTS
Western blot (wb)
Detects antibodies to individual HIV proteins and glycoproteins
that have been separated into discrete bands by electrophoresis.
Positive WB is dened as the presence of at least 2 of the p24,
gp41,and gp120/gp160 bands.
The absence of all bands is considered a negative test.
An indeterminate test has a single band or a combination of
bands that does not t the interpretation of positive.
Indirect immunouorescence assay (ifa)
A qualitative glass slide test used to conrm the presence of
serum HIV-Ab Results are equivalent to WB.
Detection of viral antigens, virus, or viral genes
HIV p24
A core protein of HIV that can be detected intermittently in the
serum, mostly immediately after primary infection and again late
in the course of the disease.
FDA approved as a screening test in blood donors to shorten
the window period and may have a role in diagnosing patients
with passive transfer of HIV-Ab, particularly infants born to HIVinfected mothers.
Polymerase chain reaction (PCR) and branched-chain DNA
(B-DNA)
Detects minute amount of HIV nucleic acids.
Viral nucleic acid detection is used to monitor progression of HIV
disease and effectiveness of antiretroviral therapy and in early
conrmation of HIV-1 infection.
Hiv isolation in cell culture
Highly specic but relatively insensitive.
A positive culture is diagnostic of HIV infection
A negative culture from those with documented infection or
someone at risk, but whose serologic results are indeterminate,
may not be reliable.
23
HIV TESTING
REPORTING REQUIREMENTS:
AIDS is reportable by name in all states. Most states have laws

or regulations requiring condential reporting by name of all
persons with conrmed HIV infection.
24
INITIAL WORKUP OF HIV

STANLEY LEWIS, MD
WORK - UP
25

ACUTE RETROVIRAL SYNDROME
Acute retroviral syndrome represents the initial viral burst of

seroconversion.
Often presents at a mononucleosis or u-like illness.
Recalled by ~50%-90% of patients.
Acute symptoms may last from few days to >10 weeks; average
duration <14 days.
Severity and duration of the acute syndrome may have
prognostic implications; severe and prolonged symptoms are
correlated with rapid disease progression.
Most common signs and symptoms include: fever,
lymphadenopathy, pharyngitis,and rash.
Many experience fatigue, headache, myalgia, arthralgia, aseptic
meningitis, retro-orbital pain, weight loss, depression, diarrhea,
night sweats, and oral or genital ulcers.
Physical exam ndings may include: morbilliform rash (or
maculopapular), usually involving the trunk, face, extremities,
including pales/soles; mucocutaneous ulceration, involving the
buccal mucosa, gingiva, palate, esophagus, anus, or penis;
hepatoslenomegaly; thrush; peripheral neuropathy; facial palsy;
psychosis. All are highly suggestive of acute infection in persons
with high risk behaviors or compatible history.
Primary HIV Infection, with or without the signs/symptoms of
acute retroviral syndrome, lasts 2-6 months while viral replication
establishes a set-point or plateau.
WORKUP OF ESTABLISHED HIV INFECTION

Differential diagnosis:
Acute HIV-1 infection should be included in the differential
diagnosis of any unexplained or complicated febrile illness.
Nonspecic symptoms often dismissed as viral syndrome by
emergency or primary care providers.
Other viral illness: inuenza, infectious mononucleosis, hepatitis
A or B, roseola, CMV, HSV.
Bacterial infections: tularemia, tuberculosis, meningococcus
Other infectious: secondary syphilis, toxoplasmosis, malaria,
trichinosis, Lyme disease.
Non-infectious: lymphoma, juvenile RA, SLE, sarcoidosis
Drug reaction: phenytoin, sulfonamides, dapsone
26

Diagnosis:
Not diagnosed by standard serologic tests; ELISA usually
negative in persons who present with acute infection.
Serologic tests rst become positive approximately 22-27 days
after acute infection.
Tests for use at home also rely on antibody production and will
not detect acute HIV-1 infection. The detection of viral RNA
(greater than 10,000 by RT-PCR) or p24 antigen in a patient with
a negative test for HIV-1 antibodies establishes the diagnosis of
acute HIV-1 infection.
HIV ELISA and HIV-1 RNA tests should be repeated 2-4 weeks
after the resolution of symptoms in high-risk persons.
Management/Treatment:
Supportive treatment for symptoms of acute retroviral syndrome.
Although controversial, most clinicians treat primary HIV infection
(with or without symptoms of acute retroviral syndrome).
Rationale for antiretroviral therapy in primary HIV infection:
decrease acute symptoms, preserve immune function, reduce
viral dissemination; reduce rate of progression; reduce rate of
mutation; reduce transmission.
Resistance testing should be considered in primary HIV infections
as initial viral isolates represent a relatively homogeneous swarm
of virus.
Optimal duration of therapy has not been determined.
If treatment initiated, it should be done with the goal of complete
suppression of viral replication (as recommended for treatment of
chronically infected) and the assumption of lifelong therapy.
If initiation of treatment delayed beyond six months, management
per chronically infected recommendations.
History
Past Medical History with focus on infectious diseases/immune
compromise including: mononucleosis-like illness (acute retroviral
syndrome), varicella zoster, tuberculosis, syphilis and other
STDs, hepatitis, HSV, candidiasis, meningitis, chronic diarrhea,
recurrent bacterial illness, PCP, toxoplasmosis, histoplasmosis,
coccidioidomycosis.
HIV risk factors including blood transfusion between 1977-1985.
Hospitalization/surgeries.
Childhood and adult illnesses and immunizations.
27

Medications: standard and alternative therapies including OTC
and dietary supplements.
Drug allergies.
Social (use of street drugs, unprotected intercourse, IVDU).
Occupational history (exposure risk)
Travel (domestic and foreign).
Pet or other animal exposure.
Women: Gynecological history, pregnancy.
Review of systems and physical examination
General: fatigue, weight loss, fever, chills, night sweats,
persistent diarrhea.
Visual: decreased visual acuity, new oaters, visual eld cuts,
and photophobia.
Oral/dental: routine care, gingivitis, dental abscesses, thrush,
leukoplakia, ulcerative lesions.
Lymph nodes: regional vs generalized, rapidly enlarging or
chronic pain, draining sinus tracts.
Cardiopulmonary: dyspnea, cough, sputum production, chest
pain, and history of abnormal chest radiographs.
Abdominal: symptoms of esophagitis, hepatosplenomegaly,
diarrhea, abdominal pain, jaundice.
Anorectal: rectal pain, discharge, mass, bleeding, ulcerations.
Genitourinary: STDs (ulcers, urethritis, discharge), PID, abnormal
Pap smears, condylomata.
Hematological: anemia, thrombocytopenia, or neutropenia.
Neurological: focal decits, seizures, neuropathy, and dementia.
Dermatological: zoster, molluscum, Kaposis sarcoma,
condylomata, skin rash, ulcerative lesions, seborrheic dermatitis,
pruritus, scabies, pigmented lesions.
Initial/baseline diagnostic testing
Conrm HIV status (ELISA, Western Blot)
CD4/CD8 subsets.
HIV viral load (PCR; b-DNA).
CBC with platlets/differential.
Routine blood chemistries, liver function tests.
PPD skin testing.
Chest radiograph.
Serologic tests for syphilis.
Hepatitis B screen (HBsAb, HBsAg, anti-HBc), HAV, HCV-Ab.
28

Lipid panel.
Women: Pap smear, screening for C. trachomatis and N.
gonorrhoeae.
Obtain if clinically indicated:
Toxoplasma IgG titer.
G6PD level (African Americans and patients of Mediterranean or
African descent).
Resistance Testing (genotype; phenotype) controversial (consider
if: source known to be taking antiretrovirals, suspect acute
retroviral syndrome, or level of baseline resistance in community
> or = 5%).
Amylase/lipase.
Ophthalmologic exam.
Dental exam.
Screen for depression/psychiatric illness.
The following tests should not be routinely obtained:
CMV titers.
EBV titers.
Thyroid function tests.
p24 Ag.
2 microglobulin or neopterin.
ESR.
B12 and folate level.
Testosterone serum level.
Immunologic prophylaxis
Hepatitis A vaccine.
Hepatitis B vaccine (if negative screens).
Pneumococcal vaccine (boost every 5 years)
Inuenza vaccine annually.
Td series or booster (boost every 10 years).
MMR (if the patient did not receive the primary series).
The following live vaccines are contraindicated
BCG.
Oral polio vaccine (OPV).
Oral typhoid vaccine.
Varicella zoster vaccine.
29

Yellow fever (risk/benet analysis for HIV positive with replete
immune system and travel to endemic area with high risk of
exposure).
The following inactivated vaccines can be used if indicated
Polio vaccine (eIPV).
Typhoid (Vi-polysaccharide).
Rabies.
The following immune globulins are recommended as indicated
IG is recommended for exposure to HAV or impending travel to
HAV-endemic areas. It is also recommended for HIV-patients
exposed to measles, regardless of immunization status.
Varicella zoster immunoglobulin (VZIG) is recommended for
susceptible patients after signicant exposure to varicella.
Tetanus immunoglobulin (TIG) is recommended for those with
serious wounds and <3 doses of tetanus toxoid or major tetanus
prone injury.
Hepatitis B immunoglobulin (HBIG) is recommended within 7
days after exposure to HBV (if not already immune).
Rabies immunoglobulin (HRIG) plus rabies vaccine series are
recommended for post exposure prophylaxis of persons not
previously vaccinated against rabies.
30
ANTIRETROVIRAL THERAPY
PHILIP KEISER, MD
31
HIV LIFE CYCLE
HIV-1 invades CD4 cells by binding of HIV-1 gp-120 and the CD4
molecule expressed on surface of the cell.
HIV-1 gp-41 interacts with cellular co-factors such as CCR5
fusing the viral envelop with the cell membrane.
In the cytoplasm, HIV reverse transcriptase uses the HIV-1 RNA
to make a double stranded DNA
HIV-1 DNA is transported into the nucleus of the CD4 cell and
inserted into the cellular DNA through the action of an HIV
integrase.
HIV-1 RNA is synthesized from the HIV DNA
HIV-1 proteins are synthesized as a single, long proto-protein.
HIV-1 proteases cleave the proto-proteins into component
proteins, completing HIV-1 maturation.
HIV-1 proteins and RNA are packaged into viral particles that bud
from the CD4 cell.
HIV-1 Pathogenesis
HIV infection is characterized by persistent viral replication.
Budding of HIV-1 from CD4 cells causes CD4 cell lysis.
CD4 cell production increases in response to CD4 loss.
An equilibrium develops between viral replication and CD4 cell
loss, resulting in a stable rate of viral replication known as a viral
set-point
Viral set-points vary widely among infected individuals, with those
with the highest set-point progressing to AIDS most rapidly.
Individuals with viral loads below level of detection have very
slow loss of CD4 cells and may not develop symptomatic HIV
infection.
Antiretroviral therapy can reduce viral replication to below level of
detection in up to 85%
Reduction of HIV-1 viral load is associated with increases of CD4
count of perhaps hundreds of cells.
Antiretroviral Drugs (See Table: Antiretroviral Drugs)
There are 20 available antiretroviral medications, in 4 classes.
Nucleoside analogue reverse transcriptase inhibitors (NRTIs)
are analogues of naturally occurring nucleosides that inhibit
conversion of HIV-1 RNA to DNA by chain termination.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) directly
bind to the HIV-1 reverse transcriptase enzymes active site,
32
irreversibly inhibiting it.
Protease inhibitors (PIs) bind to the active site of the HIV-1
protease enzyme, blocking its cleavage of HIV-1 proteins.
Entry inhibitors block the interaction between HIV-1 gp-41 and
CD4 cell co-factors, preventing fusion between the virus and the
cell.
33
34
35
36
37
38
PRINCIPLES OF HIV THERAPY
Antiretroviral therapy can decrease HIV-1 viral replication
resulting in increased CD4 cell counts, decreased opportunistic
infections, decreased neoplasms and prolonged survival.
Long term therapy is associated with diabetes mellitus,
hyperlipidemia, lactic acidosis and lipodystrophy.
Treatment of HIV-1 is usually deferred until HIV is symptomatic
or CD4 declines to a point below which the patient is likely to
become ill in next several years.
Treatment involves balancing benets of antiretrovirals with risks
of toxicity and viral resistance.
Viral resistance occurs at a predictable rate after initiation of
treatment.
GOALS OF HIV THERAPY

Maximal suppression of HIV-1 RNA for the longest possible
duration
Improvement of CD4 cell counts
Decreases in HIV-1 related morbidity and mortality
Recommended Treatment Initiation Paramenters

Clinical Syndrome
Symptomatic AIDS
CD4 Cell Count
HIV-1 RNA
Recommendations
Any
Any
Treat
Asymptomatic HIV
< 200
Any
Treat
Symptomatic HIV
200 - 350
Any
Treat
Asymptomatic HIV
> 350
> 55,000
Treat
Asymptomatic HIV
> 350
< 55,000
Do not Treat
Adapted from DHHS Treatment Guidelines
39
ADHERENCE TO ANTIRETROVIRAL MEDICATIONS
HIV therapy is lifelong commitment to taking medications

Minimum 85-90% adherence required to maintain virologic
suppression and prevent resistance
Assess potential for adherence prior to initiation to obtain best
results
Patients judged poor adherence risks should have therapy
delayed as long as medically appropriate or until patient
demonstrates readiness to adhere
Factors that can improve adherence
s Good Doctor-Patient relationship
s Education of patient as to benets and side effects of
antiviral therapy
s Anticipation and treatment of side effects
s Treatment of depression and substance abuse
s Multi-disciplinary staff support for adherence education
s Use of organizers and reminders: pill boxes, etc.
s Use of simple regimens, preferably qday.
INITIAL ANTIRETROVIRAL THERAPY
Highly active antiretroviral therapy (HAART) consists of an active

agent (i.e., a PI or a NNRTI plus two NRTIs).
More intense regimens, (e.g., 4 or more drugs) caused increased
toxicity; not used as initial therapy
Triple nucleosides, eg ABC/3TC/AZT or ABC/3TC/TNF
associated with high failure rates and should not be used as
initial therapy without an additional active agent.
Preferred regimens are those with the best rates of viral
suppression, best toxicity proles and lower pill burdens.
Alternative regimens can also have similar effectiveness but may
have higher pill burdens, higher toxicity rates or lower rates of
virologic suppression.
Initial regimens will inuence the choice of subsequent regimens
because of subsequent cross resistance or overlapping toxicities.
ANTIRETROVIRAL THERAPY SHOULD BE INDIVIDUALIZED.
40
Preferred and Alternative Initial Regimens
Active Agent
Preferred
Regimens
Alternative
Regimens
Efavirenz
Nucleoside Analogues
TNF + 3TC
or
d4T + 3TC
or
AZT + 3TC
Qday Regimen/
Pill Count
Yes/ 3
No/4 or 5
No/3
Lopinivir/
Ritonavir
d4T + 3TC
or
AZT + 3TC
Efavirenz
ddI + 3TC
or
ABC/3TC combo pill
or
TNF/FTC combo pill
Yes/3
ABC/3TC combo pill

or
TNF/FTC combo pill+
or
TNF+3TC+
or
d4T + 3TC
or
AZT + 3TC
or
d4t + FTC
Yes/3-4
Atazanavir
(+/- ritonavir
boosting)
No/ 9-10
No/9-10
Yes/2
Yes/2
Yes/4
Yes/5-6
No/6-7
No/4-5
No/6-7
Nelnavir
d4T + 3TC
or
AZT + 3TC
No/13-14
Indinavir +
Ritonavir
d4T + 3TC
or
AZT + 3TC
No/9-10
Saquinavir +
Ritonavir
d4T + 3TC
or
AZT + 3TC
No/15-16
Nevirapine
d4T + 3TC
or
ddI + 3TC
or
AZT + 3TC
No/5-6
No/12
No/8
No/14
No/4
No/4
*Atazanavir is a preferred agent in the International AIDS Society - USA treatment

guidelines but is an alternative in DHHS Guidelines
*Atazanavir must be boosted with 100mg of ritonavir when combined with tenofovir
41
MONITORING OF ANTIRETROVIRAL THERAPY
CD4 counts and HIV-1 RNA viral load should be monitored every
3 months. Most HIV experts will see the patient at one month
after starting therapy to assess toxicity, adherence and HIV-1
RNA decline.
HIV-1 RNA should decrease by 1 log in 12 weeks and should be
below levels of detection by 24 weeks. CD4 recovery may take
longer.
Specic toxicities for particular anti-retrovirals should be
monitored by selected testing. Typically, CBC, electrolytes, BUN,
creatinine, LFTs and glucose are monitored every 3 months.
Lipids should be monitored every 6 months.
CHANGING THERAPY
Adherent patients who fail to achieve an undetectable HIV-1 RNA

or who have a rebound in HIV-1 RNA should be considered for a
change in therapy.
Viral rebound should be conrmed by a second HIV-1 RNA test.
Potential reasons for failing therapy include:
Poor adherence
Malabsorption/insufcient levels
Toxicity
Emergence of resistance
Adherence and toxicity issues should be addressed prior to
considering changing medication.
Resistance testing should be performed while on failing regimen
and prior to changing therapy.
Choice of new drugs should be based on results of resistance
tests and experience with past antiretroviral therapy.
Optimally, patients should be treated with at least 3 new drugs to
which the patients virus is susceptible.
For patients who had toxicity to a particular agent, new drugs with
overlapping toxicities should be avoided.
Monitoring of patients should continue.
After 2 regimen sequences, broad cross resistance typically
occurs, diminishing treatment options.
42
Potential Sequencing of Antiretroviral Regimens
First Regimen
2nd Regimen
3rd Regimen
2 NA + NNRTI
2 NA + Dual PI
NA + PI + Entry Inhibitor
2 NA + PI
2 NA + NNRTI
NA + Dual PI
2 NA + PI
2 NA + NNRTI + PI
NA + PI + Entry Inhibitor
CLASS/AGENT SPECIFIC ISSUES

NRTI
Thymidine analogues (AZT and d4T) should never be used together
because of antagonistic effects
D4T, ddI, ddC should not be used together because of overlapping
toxicity.
Tenofovir has interactions with a variety of antiviral medications
such as ddI (increases) and atazanavir (decreases). Dosages of
these medications should be adjusted.
NNRTI
NNRTIs share signicant cross resistance, effectively eliminating
sequencing these agents.
Rashes are not cross reactive, thus these agents can be
substituted.
Efavirenz should be avoided in pregnant women because of risk of
anencephaly.
Nevirapine causes high rate of hepatitis in patients with HCV
co-infection, pregnant women & in CD4 courts HCV > 250.
PI
While there is broad cross resistance among protease inhibitors,
several agents have signature mutations that allow for sequencing.
NLF failures often sensitive to other PIs and can be salvaged with
SQV/RTV or Kaletra.
ATZ failures are often sensitive to other PIs; little clinical data on
salvage with this regimen.
Best results with PI failures occur in patients next treated with an
NNRTI and a PI
Entry Inhibitors
Must be used with other antiretrovirals for maximum effectiveness.
Best results occur in patients with virus sensitive to at least 2 agents.
Little data on efcacy in antiretroviral nave patients.
43
44
RESISTANCE TESTING
DAVID MARGOLIS, MD
45
RESISTANCE TESTING
RESISTANCE TESTING ASSAYS
Advantages
Disadvantages
Genotypic assays:
Determine
the nucleotide
sequence of
the protease
and reverse
transcriptase genes
by amplication of
PR and RT viral
RNA in plasma.
Identify mutations
which have
been associated
with treatment
failures, an indirect
measure of
resistance.
Focus on parts of
the HIV genome,
may miss novel
mutations.
Relatively simple to
perform.
Widely available
Rapid turn-around
time.
Allow detection of
sentinel mutations
prior to change in
phenotype.
Insensitive to
presence of minor
variants.
Interpretation
requires prior
knowledge
of genetic
determinants of
resistance.
Cannot predict
effect on phenotype
of mutational
interactions.
Advantages
Disadvantages
Phenotypic assays:
Determined by the
amount of drug
required to inhibit
virus production in
vitro by 50%.
Do not test the
patients virus in
human cells, but
rather the function
of amplied
fragments of PR
and RT genes in a
standardized cell
line system.
Assess net effect

of mutations on
drug susceptibility.
Provide data on
cross-resistance.
Insensitive to
presence of minor
variants.
Time-consuming
and expensive to
perform.
Complexity of
the assays limits
availability outside
a small number of
laboratories.
Slow turn-around.
46
RESISTANCE TESTING
RESISTANCE TESTING ASSAYS
Virtual Phenotype: This is a genotype with an algorithmgenerated estimate of what the phenotype would be. These
estimates are generated by matching the genotype from the
patients sample to genotypes and their matched phenotypes in a
database of clinical isolates.
Resistance Testing Limitations
Resistance testing, while patients are off HAART, may yield
misleading results.
The current assays are unable consistently to detect minority
quasi-species. Thus, resistant strains that represent a small
proportion of the total viral pool may not be identied.
Technical expertise varies, particularly in the detection of
minority species.
Novel mutations can confer resistance to some drugs
particularly when novel drug combinations are used.
47
RESISTANCE TESTING
RESISTANCE TO NUCLEOSIDE RT INHIBITORS (NRTIS)
AND NUCLEOTIDE RTIS (NTRTIS):
High-level resistance by single mutation:
Lamivudine (3TC) M184V mutation at confers high-level
resistance to 3TC, which can be detected within weeks of
initiation of therapy. The M184V mutation however, confers AZT
partial susceptibility in AZT-resistant mutants. Co-administration
of AZT and 3TC delays emergence of resistance to AZT. MDR
HIV with many mutations to NRTIs can be 3TC-resistant despite
the absence of M184V. G333D or E is a new mutation recently
recognized to correlate with high-level resistance to AZT or 3TC.
Clinically signicant cutoffs for sensitivity in phenotypic assays
well-dened
Emtricitabine (FTC). Resistance is identical to that of 3TC.
High-level resistance following several mutations:
Zidovudine (AZT). Resistance to AZT increases as more
mutations are acquired. Mutations at codons M41L, D67N,
K70R, L210W, T215Y or F, and K219Q or E or N result in a 50- to
1000-fold increase in the AZT-IC50. These nucleoside analog
mutations (NAMs) can cause cross-class resistance if several
are present. G333D or E is a mutation recently recognized to
correlate with high-level resistance to AZT or 3TC.
Didanosine (ddI). Mutation at codon 74 emerges after 6 to
12 months of ddI monotherapy and confers modest reduction
in antiviral activity. Introduction of the L74V mutation into RT
genes that also carry the T215Y mutation restores susceptibility
to AZT. Emergence of the codon 74 mutation is prevented or
delayed in patients treated with ddI in combination with AZT.
Conversely, emergence of AZT resistance was not delayed by
the combination. The K65R mutation also confers ddI resistance.
Zalcitabine (ddC). The clinical signicance of ddC resistance
mutations remains uncertain.
Stavudine (d4T). Mutations that confer AZT resistance also
confer resistance to d4T, but are not as often selected primarily
by d4T therapy. Mutations at 75 or 178 confer resistance to d4T,
but are not reported frequently.
Abacavir (ABC). Mutations at codons 65, 74, and 115 result in
ABC resistance. By itself, the presence of the M184V mutation
48
RESISTANCE TESTING
does not seem to adversely affect the virologic response to ABC.
The presence of more than 3 NAMs or 2 NAMs and 184 predicts
poor response to ABC.
Tenofovir (TNF). TNF exposure selects for K65R mutation,
conferring resistance. In drug-experienced patients, similar to
ABC, TNF has extended activity against viruses encoding several
NAMs. Patients with M184V respond somewhat better to TNF.
Multi-nucleoside drug resistance:
Most frequently, MDR is due to the presence of multiple ( 4)
NAMs.
K65R gives resistance to ddI, ABC, ddC, and TDF but not AZT or
d4T
Mutation at Q151M confers resistance to all available NRTIs.
The prevalence of Ql5lM is low.
T69S-S insertion mutation confers resistance to all available
NRTIs, and develops after prolonged treatment with multiple
NRTIs.
Resistance to Non-nucleoside RT Inhibitors:
The K103N mutation gives high-level resistance to all NNRTIs.
Other mutations at 100, 106, 108, 181, 188, 190, and 225 can
be selected prior to k103N.
In general, any NNRTI mutation is associated with poor
subsequent response to currently available NNRTIs, and
continued NNRTI therapy leads to the emergence of K103N.
PROTEASE INHIBITORS:
Saquinavir (SQV). Primary G48V and L90M mutations confer
a 2-6-fold reduction in susceptibility to SQV. Addition of more
mutations increases cross-resistance to other PIs.
Ritonavir (RTV). The primary mutation usually appears at
codon 82.
Indinavir (IDV). Primary mutations at codon 46 or 82 correlate
most commonly with clinical failure. Measurable resistance
requires the presence of >3 mutations. Addition of more
mutations increases cross-resistance to other PIs.
Nelnavir (NFV). The D30N or L90M mutation is the rst to
emerge in patients failing NFV. Early NFV failures with D30N
can respond to other PIs.
49
RESISTANCE TESTING
Amprenavir (APV). The I50V mutation is the rst to emerge
in patients failing APV without RTV. Early APV failures without
additional mutations can respond to other PIs.
Lopinavir (LPV). For high-level resistance more than 3 of: 20,
24, 50, 53, 54, 73, 82, 84, 90 (primary); or 10, 32, 46, 47, 63, 71
(secondary) required.
Atazanavir (ATZ). The I50L mutation (distinct from I50V of APV)
is the rst to emerge in patients failing ATZ without RTV. Early
ATZ failures without additional mutations can respond to other
PIs. ATZ/RTV therapy can select isolates that carry additional
mutations, increasing the possibility of cross-resistance.
USEFUL WEBSITES FOR INTERPRETING GENOTYPES AND FOR

FURTHER INFORMATION:
http://hivdb.stanford.edu
http://www.iasusa.org/resistance_mutations/index.html
RECOMMENDATIONS: APPLICATION OF HIV DRUG RESISTANCE

TESTING
1. Resistance testing should be used to explain and manage
treatment failure.
2. Resistance testing should be used to track prevalence of drug
resistance in primary HIV infection.
3. Resistance testing should be considered in the setting of primary
HIV infection or in specic settings (e.g. urban settings with high
prevalence of transmission of drug-resistant HIV; healthcare
worker exposure). The role of resistance testing in chronically
infected, treatment-nave patients is not clear.
50
MANAGEMENT OF PERSONS EXPOSED TO HIV

PHILIP KEISER, MD
51

PRINCIPLES OF POST-EXPOSURE PROPHYLAXIS FOR HIV
HIV has been transmitted to health care workers primarily by

exposure to blood CSF, pleural and peritoneal uid. Semen and
vaginal secretions also have high levels of virus
Saliva, sputum and tears have little or no virus and are not
considered infectious.
Percutaneous stick with a hollow bore needle containing HIV
positive uid has a 1/250 chance of transmission of HIV.
High viral load in the source is associated with greater risk of
transmission.
Cases of transmission with non-hollow bore needles have been
reported but transmission occurs at such a low frequency that a
risk cannot be calculated.
Exposure of membranes (eye, mouth) to large volumes of blood
rarely associated with transmission.
Prompt treatment of an exposed individual with anti-retroviral
medications may reduce the risk of transmission to almost zero.
Prophylactic therapy can be poorly tolerated however, and the
decision to treat with anti-retrovirals should balance the risk of
infection with the toxicities of medications.
RISK ASSESSMENT
Nosocomial exposure to HIV infection is best managed in

consultation with an expert with experience in treating HIV.
The sero-status of the source patient should be established. HIV,
HBV HCV serology an RPR should be sent.
Awaiting serologic test results of source patients who have
limited risk of HIV infection, prophylaxis for injured workers can
be delayed until results are obtained. For high risk exposures
to source patients with known or suspected HIV, therapy should
begin immediately.
Risk of transmission based on exposure should be determined
HIGH: percutaneous stick with hollow bore needle containing
blood, pleural uid, peritoneal uid or CSF, or an exposure of
an open wound to these uids.
INTERMEDIATE: exposure of mucous membranes or eyes
with blood or body uids that have high levels of HIV.
LOW: any other type of exposure. Examples include blood on
intact skin, exposures to urine, stool or saliva.
HIGH RISK exposures should receive prophylaxis.
52

INTERMEDIATE RISK exposures may receive prophylaxis,
depending on the nature of the exposure and the interest on the
part of the exposed individual in taking medication.
LOW RISK exposures should not be treated.
THERAPY FOR EXPOSURE
Therapy for should be initiated as soon as possible after the

exposure.
Therapy should be continued for 28 days after exposure.
Preferred current regimen for HIV exposure is AZT-3TCNelnavir.
D4T or Tenofovir may be substituted for AZT.
Efavirenz may be substituted for Nelnavir.
Nevirapine should not be used for prophylaxis because of several
cases of hepatic failure requiring liver transplantation.
Genotypic resistance testing of the source patient to guide
prophylactic therapy of the exposed person should be used
when the source patient has a signicant history of anti-retroviral
experience or known genotypic resistance.
53
54
DERMATOLOGICAL COMPLICATIONS
LAURA WINTERFIELD, MD
55
56
57
58
59
60
61
62
63
64
PULMONARY COMPLICATIONS
M. SHAHBAZ HASAN, MBBS
65
PNEUMOCYSTIS CARINII PNEUMONIA (PCP)
P. carinii causes a slowly (1-4 weeks) progressive pneumonia
with non-productive cough, dyspnea, fever, sweats, and weight
loss, which occurs almost exclusively in patients with CD4
<250L
New nomenclature is Pneumocystis jiroveci. Technically, it is a
fungus.
Incidence has declined markedly in the post-HAART era
Should be suspected in any HIV patient with respiratory
symptoms.
Diagnosis
DLCO is a sensitive but non-specic test for PCP. Normal DLCO
virtually excludes PCP.
Exercise-induced O2 desaturation is probably the most sensitive
and specic non-invasive test for the diagnosis of PCP. The
test is cheap, easy to perform, and is not affected by PCP
prophylaxis. A normal test virtually excludes the presence of PCP.
An exercise induced desaturation to 90% or less in association
with typical bilateral central interstitial inltrate on CXR is highly
predictive of PCP.
Moderate-large pleural effusion or mediastinal or hilar
lymphadenopathy is rare in PCP and suggests other diagnoses
such as bacterial infection, TB, or malignancy.
Organisms are almost never seen in patients who are truly free of
all symptoms and CXR abnormalities. For patients who received
aerosolized pentamidine prophylaxis, the yield of induced sputum
is reduced by about 20%.
Etiologic diagnosis of respiratory disease in AIDS relies on
early induced sputum or bronchoscopy. Precise microbiologic
or histologic conrmation remains important, especially in
patients in whom a diagnosis of PCP is less likely due to prior
chemoprophylaxis. Etiologic diagnosis is conrmed by Direct
Fluorescent Antibody (DFA) staining of the respiratory samples.
Multiple infections are often present simultaneously with PCP.
CXR may appear normal in early disease. With more advanced
illness diffuse alveolar and lobar inltrates, cavities or cysts and
even pneumothorax may be seen.
66
Treatment
Isolation of patients with , PCP is not required.
Trimethoprim-Sulfamethoxazole (TMP/SMX) 15-20 mg/kg/day
IV or PO (of the TMP component) in 3-4 divided doses for 21
days is the treatment of choice. TMP/SMX has the advantage of
excellent tissue penetration, rapid clinical response (3-5 days),
and excellent oral bioavailability.
Response to appropriate therapy may be slow, especially with
severe respiratory compromise or underlying lung disease.
Response is generally excellent in patients diagnosed prior to
respiratory failure.
Radiologic appearance lags behind clinical deterioration or
improvement.
Successful treatment of breakthrough infections occurring
in patients receiving prophylaxis can be achieved by using
the same agent used for prophylaxis, except aerosolized
pentamidine.
Corticosteroids should be used in moderate-severe PCP (PO2
<70 torr, A-a gradient >30). The usual dose is prednisone 40 mg
PO BID for 5 days; 40 mg PO QD for 5 days, then 20 mg PO for
11 days. The risk of respiratory failure and death is reduced by
50%.
Treatment failure with an accepted regimen (4-5 days on TMP/
SMX, or 5-7 days on pentamidine) is uncommon, and changing
therapy other than for toxicity is not generally indicated.
Alternative Therapy
Dapsone 100 mg PO QD + trimethoprim 15-20 mg/kg/day PO for
21 days.
Clindamycin 450-900 mg IV or PO QID + primaquine 15 mg base
PO QD for 21 days (almost as effective as TMP/SMX).
Pentamidine 4 mg/kg/day IV for 4-5 days then 3 mg/kg/day for
the remainder of a 21 day course.
Atovaquone suspension 750 mg PO BID for 21 days (for mild to
moderate PCP).
Prophylaxis
Recommended for patients with history of previous PCP, CD4
<200/L, history of recurrent candidiasis, unexplained fever of
100F for >2 weeks, or rapid fall in CD4 count, using one of the
following (listed in descending order of efcacy):
67
TMP/SMX one double strength (DS) PO QD or 3 times weekly
Dapsone 100 mg PO QD.
Nebulized pentamidine 300 mg/2-4 weeks (Respirgard
nebulizer only).
Atovaquone suspension 1500 mg PO QD.
Pentamidine 4 mg/kg/month IV.
In pregnancy, TMP/SMX is the recommended prophylactic agent.
Because of theoretical concerns regarding possible teratogenicity
associated with TMP/SMX exposure during the 1st trimester,
aerosolized pentamidine should be used.
Disseminated pneumocystosis, with involving liver, spleen, bone
marrow or eyes, and PCP involving the lung apices reported in
patients receiving inhaled pentamidine.
Desensitization Protocols For TMP/SMX
Up to 50% of AIDS patients may be allergic or intolerant to TMP/
SMX. These patients can be treated with an alternative regimen
or desensitized (~80% successful).
Patients with severe TMP/SMX allergies (anaphylaxis, severe
rash, fever, bone marrow suppression) should be excluded.
Patients tolerating desensitization should be continued on TMP/
SMX DS for PCP prophylaxis.
Discontinuation Of Prophylaxis
PCP prophylaxis can be safely discontinued in patients
responding to HAART with both a sustained increase in CD4
counts to >200 cells/L, and sustained reduction in viral load for
at least 36 months.
TUBERCULOSIS
Worldwide, reported prevalence of TB in AIDS ranges from

4-44% in different populations.
Compared to non-HIV-infected patients, HIV/TB have higher
rates of primary disease skin test anergy, extrapulmonary TB
(50%).
Patients with higher CD4 usually present in classic fashion
whereas those with low CD4 are more likely to present atypically:
e.g. atypical pulmonary inltrates; abscesses of brain, breast, or
viscera; x; bacteremia; skin lesions.
68
Diagnosis
HIV patients with pulmonary TB may present with atypical CXR.
Lobar inltrates usual (hilar adenopathy or diffuse interstitial
inltrate, resembling PCP, may be seen). CXR normal in~10-20%
of AIDS-associated pulmonary TB; cavitary disease much less
common, possibly reecting overall immune dysfunction with
advanced HIV.
AFB stain: uorochrome stain is the preferred acid fast stain; as
sensitive (50%) and specic as basic fuscin stains and can be
rapidly interpreted.
AFB culture.
PCR of sputum (50-100% sensitive, 95-100% specic).
Prophylaxis
Tuberculin skin test (TST), using intermediate-strength (5-TU)
PPD, should be part of the initial evaluation of all HIV patients.
Anergy testing not recommended.
HIV patients with positive PPD have 5-8% annual risk and ~30%
lifetime risk of developing TB if untreated.
In absence of active TB, INH plus pyridoxine daily or twice
weekly for 9 months recommended for all HIV patients with >5
mm induration on PPD and who have not previously been treated
for TB.
HIV-infected close contacts of persons with infectious TB should
be ruled out for active TB then receive TB prophylaxis regardless
of their TST results or prior courses of prophylaxis. If initially
nonreactive, TST should be repeated again 3 months after
contact with the infectious case.
Rifampin and PZA are associated with hepatotoxicity and should
be avoided except in the case of exposure to multidrug resistant
TB (MDR-TB).
TB chemoprophylaxis is not contraindicated in pregnancy.
Except for exposure to MDRTB, INH is prophylactic agent of
choice. Experience with rifamycins during pregnancy limited,
but anecdotal experience suggests thatrifampin does not cause
adverse fetal outcomes.
BC G (live-attenuated vaccine) is not recommended in HIVinfected patients because of risk of disseminated BCG.
69
Treatment
During workup for TB patients should remain on airborne
precautions until TB is ruled out or has been effectively treated,
patients condition improving clinically, and 3 consecutive sputum
AFB smears on different days are negative.
CDC recommends all TB patients receive directly observed
therapy (DOT) to reduce noncompliance and prevent emergence
of drug-resistant strains.
Initial treatment 4 drugs until culture and susceptibility available.
INH
Rifampin
Ethambutol
PZA
If TB isolate fully susceptible, INH and rifampin continued for
additional 9 months, or at least 6 months beyond last positive
culture. However, optimal length of therapy for HIV infected TB
patients not established. Especially important to assess clinical
and bacteriologic response when treating HIV patients; treatment
should be prolonged beyond 6 months if response is slow or
suboptimal.
Combination preparations (Rifadin, Rifamate) may be considered
to increase compliance and thus decrease the emergence of
resistance.
Only meningitis, osteomyelitis, and miliary TB need prolonged
therapy. Treatment of disease at other extrapulmonary sites
(lymph nodes, pleura) follows recommendations for pulmonary
TB.
Chronic suppressive therapy for patient successfully completing a
recommended regimen of TB treatment not necessary.
Rifampin generally contraindicated in persons taking protease
inhibitors (PIs) or NNRTIs. Rifabutin can be substituted for
rifampin in some circumstances; rifabutin can safely be used with
IDV, NLF, APV, RTV, and EFV, but not with hard-gel SQV, or DLV.
Caution advised if rifabutin administered with soft-gel SQV or
NVP.
Rifabutin 50% of usual daily dose (150 mg/day) with IDV, NFV,
or APV, or at 25% of the usual dose (150 mg every other day or
three times a week) with RTV. Daily rifabutin dose 450 mg or 600
mg when used with EFV; might be given at usual doses with NVP.
For patients receiving multiple PIs or PI combined with NNRTI,
interactions with rifabutin more complex, so avoid use of rifabutin.
70
Multidrug Resistant Tuberculosis (MDR-TB)
Suspect MDRTB in patients from correctional institutions or
hospitals with known outbreaks MDRTB, previous history
incomplete therapy for TB, exposure to known MDRTB, or
patients failing anti-TB therapy.
Treatment MDRTB includes 4-5 drugs to which isolate fully
susceptible and continued at least 18-24 mos. Previous therapy
with an anti-TB medication lasting for more than one month
associated with diminished efcacy of those drugs.
MDRTB in HIV associated with 35% mortality. Improved survival
associated with higher CD4 counts, non-disseminated disease,
cavitary lesions on CXR, and prompt institution of appropriate
DOT.
BACTERIAL PNEUMONIA
Bacterial pneumonia most common form of pneumonia in HIV;

10-fold higher risk of pneumococcal pneumonia than non-HIV
S. pneumoniae one of the frequent invasive bacterial infections
in HIV. IDUs particularly susceptible. Other: Haemophilus,
Moraxella, Klebsiella, N. meningitidis, Rhodococcus, S. aureus,
Nocardia. An indolent, relapsing Pseudomonas pneumonia and
bacteremia described in AIDS patients. Clinical presentation is
similar to non-HIV patients.
Radiographic changes often atypical, resembling PCP in 50%.
Sputum Gram stain and cultures by sputum induction or BAL help
diagnosis.
Prophylaxis
82% of S. pneumoniae isolates in HIV are among the
23 serotypes included in pneumococcal vaccine. Give
pneumococcal vaccine every 5 years, including in pregnancy.
TMP/SMX, in doses used for PCP prophylaxis, is effective in
preventing bacterial pneumonia in AIDS. H. inuenzae vaccine
not recommended in adults.
Treatment
Response to typical antibiotics usually rapid and clinical course
and prognosis resemble those in normal hosts.
71
INFLUENZA
Inuenza common in adults (~5%-40% of the general population),

depending on the severity of the inuenza season.
HIV patients may have higher incidence of inuenza and
complications (pneumonia, bronchitis, sinusitis, otitis).
Diagnosis
Sudden onset fever, headache, non-productive cough, and
systemic symptoms such as myalgias and malaise is typical
presentation. Inuenza A and B similar, although inuenza B may
be less severe.
Knowledge of current local epidemiologic patterns of infection is
extremely helpful in making diagnosis.
Diagnosis by viral culture of nasopharyngeal swab or aspirate,
throat swab, or sputum. Culture is highly accurate and allows
typing.
Three rapid tests are available including the Directigen Flu A, the
Biostar optical immunoassay (FLU OIA), and the Z-stat Flu test.
Treatment
Amantadine and Ramantadine act only against inuenza A, and
frequently and rapidly induce resistance.
Oseltamivir (Tamiu), an oral capsule, reduces severity of u
symptoms ~40% and secondary complications ~50%. Reduces
u in patient contacts by 90%. Oseltamivir dose for treatment 75
mg PO BID 5 days. Prophylaxis, dose 75mg PO QD 6 weeks.
Resistance is infrequent.
Prophylaxis
Inactivated inuenza vaccine safe and effective reducing
morbidity, mortality, and economic losses due to inuenza.
Inuenza vaccination has slight transient effects on the
immunologic and virologic status of HIV patients. Vaccine
immunogenic and cost-effective, although antibody titers are
lower and may decline more rapidly in HIV patients. Live
attenuated inuenza vaccine should not be used in HIV patients.
Oseltamivir effective in preventing inuenza in patients who did
not receive vaccine, are allergic to vaccine, and in outbreaks of
non-vaccine strains.
72
RHODOCOCCUS EQUI
Infection by Rhodococcus reported in patients with AIDS,

malignancy, or renal transplant.
May be associated with livestock/soil exposure.
Cough, fever, +/- hemoptysis, and chronic cavitary lesions +/pleural effusions. Must be differentiated from TB.
Readily isolated from blood, sputum, lung or pleural uid.
Treatment mainly vancomycin. Clindamycin, rifampin,
erythromycin, TMP/SMX also effective. Aminoglycosides,
imipenem, and quinolones variable results. Use double drug
therapy 4-8 weeks. Surgery may be required for persistent
abscess or lobar collapse.
CRYPTOCOCCUS NEOFORMANS
Uncommon cause of pneumonitis. May occur with or without

meningitis. Presentation similar to PCP. May be associated with
molluscum contagiosum-like skin rash.
CXR ndings are non-specic with either diffuse or focal
inltrates
Diagnosis: sputum or blood cultures or detection of antigen in
the serum.
In the absence of meningitis, treat with oral uconazole or
itraconazole.
ENDEMIC FUNGI (COCCIDIOIDES AND HISTOPLASMA)
Occasionally seen in endemic areas, arid parts of the Southwest

(Cocci) and Ohio and Mississippi River areas (Histo)
Present like PCP with an atypical pneumonitis.
May present with extra-pulmonary dissemination to meninges,
bone/joints and skin (Cocci) or fungemia, sepsis syndrome, liver,
spleen, lymph node and bone marrow (Histo).
CXR non-specic: hilar adenopathy to focal or diffuse inltrates
or thin-walled cavities.
Cocci diagnosed by stain and fungal culture of sputum, BAL or
extrapulmonary specimens. Serology less sensitive.
Histo diagnosed by antigen detection in urine (95% sensitive) or
serum (85% sen) or by stain and fungal culture of respiratory or
extrapulmonary specimens.
Treatment generally initiated with amphotericin later followed by
uconazole or itraconazole.
73
CMV PNEUMONITIS
Uncommon cause of pneumonia in HIV. Presents like PCP with

night sweats, chills, fevers, day cough, and dyspnea.
Serologic testing seldom helpful, owing to the high prevalence of
CMV infection in HIV population. Viral cultures (positive in~43%
of AIDS patients) are nondiagnostic. Tissue biopsy demonstrating
owls eye inclusions is most reliable way to diagnose.
Only biopsy-proven disease and no other pathogen to explain
pneumonia should be treated.
Ganciclovir 5 mg/kg IV Q12H for 2 weeks, then chronic
suppression with 5 mg/kg/day.
Foscarnet 90 mg/kg IV Q12H for 2 weeks, then maintenance with
90-120 mg/kg/day.
Prognosis poor.
MYCOBACTERIUM AVIUM COMPLEX (MAC)
Frequently found in sputum. Occasionally causes invasive

pulmonary disease.
KAPOSIS SARCOMA (KS)
Persistent dry cough, dyspnea, or hemoptysis, almost always

associated with KS skin lesions shows patchy nodularity, pleural
effusion; CT may show multiple lesions. Bronchoscopy usually
reveals endobronchial KS. Associated with human herpes virus8 (HHV-8). Incidence declined sharply with HAART.
Pulmonary KS differentiated from PCP and other diseases by
typical CXR ndings, normal gallium scan, bronchoscopy.
Biopsy of pulmonary KS usually avoided because of risk of
bleeding, which is actually uncommon. Biopsy often negative
as lesions are visible but submucosal. Parenchymal KS rare in
absence of endobronchial lesions.
Treatment: HAART is mainstay. Chemotherapy may be needed.
Radiotherapy may be palliative.
74
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76
77
78
GASTROINTESTINAL COMPLICATIONS
WILLIAM HARFORD, MD
79
OROPHARYNGEAL SYNDROMES
Clinical Presentation and Diagnosis
Oral candidiasis (Thrush)
Appearance may vary:
White patches that can be scraped off, leaving a red base, or
Atrophic or red patches, or
Cracking or ssuring of the corners of the mouth, or
Hyperkeratotic patches that cannot be scraped off
Symptoms: asymptomatic, or burning pain, or altered taste
Diagnosis- KOH prep
Oral hairy leukoplakia
Appearance
Asymptomatic patches and plaques on lateral tongue or
posterior pharynx that do not scrape off ; hairy tongue in
severe cases
Caused by Epstein-Barr Virus
Not premalignant
Diagnosis by clinical appearance
Herpes simplex virus
Appearance
Multiple aintal vesicles on lips, buccal mucosa, soft palate,
often ulcerated and crusting
Diagnosis by clinical appearance, Tzanck smear, culture or IFA
Periodontal disease
Linear gingival erythema
Redness and swelling along gingival margins, with pain and
spontaneous bleeding
Ulcers at tips of interdental papillae and gingival margins and
cratered appearance of gingiva after healing
Necrotizing ulcerative periodontitis
Pain, gingival ulceration, gingival and bone necrosis;
loosening and loss of teeth
Aphthous ulcerations
Painful ulceration of the mouth and/or esophagus, similar in
appearance to HSV or CMV
Dry mouth/salivary gland disease
Dry mouth may be associated with medications, e.g. ddI,
antidepressants
Salivary glands may be enlarged
80
Treatment
Oral thrush (candidiasis), oral hairy leukoplakia, herpes simplex
virus
Periodontitis
Linear gingival erythema
Periodontal referral
Irrigation with povidone-iodine
Chlorhexidine (Peridex) mouth rinse 1-2 times a day
Necrotizing ulcerative periodontitis
Periodontal referral, and
Irrigation and rinse as above, and
Metronidazole 250 mg PO 4 times a day, or clindamycin 300
mg 3 times a day, or amoxicillin/clavulanate 250 mg 3 times a
day
Aphthous ulceration
Aphthous mouth wash (tetracycline, nystatin, and lidocaine, or
Fluocinonide (Lidex) 0.05% ointment in Ora-base, or
Clobetasol 0.05% in Ora-base
For refractory cases
Prednisone 40-60 mg per day for 4-6 weeks, or
Thalidomide 200 mg per day (teratogenic!)
Dry mouth/salivary gland disease
Sugarless gum, candies, or saliva substitutes
DYSPHAGIA/ODYNOPHAGIA
Differential Diagnosis
Candida
Cytomegalovirus
Herpes Simplex Virus
Idiopathic (aphthous) ulceration
Medications (AZT, ddC)
Neoplasms
Gastroesophageal reux disease
Idiopathic motility disorders
Clinical Presentation and Diagnosis Evaluation
Therapeutic trial of uconazole for 5-7 days if:
dysphagia is the predominant symptom, and
especially if oral thrush is present.
continue uconazole if the response is satisfactory
81
Refer the patient for upper endoscopy if
odynophagia is the predominant symptom or
the response to uconazole is unsatisfactory
At upper endoscopy, obtain
brushings for cytology and/or KOH prep for Candida
If ulceration is found, take biopsies for histology
ulcer base for CMV and
ulcer edge for HSV, but
Do not send viral cultures for CMV (too sensitive, not
specic for CMV disease as opposed to colonization)
Treatment
Immune reconstitution with HAART when possible.
Candida, CMV, HSV: See Apendix 1
Idiopathic esophageal ulcers
Prednisone 40 mg daily for 2-4 weeks, then 10 mg/week
taper, or
Thalidomide 200 mg daily (teratogenic!)
DIARRHEA
Medications
Antiretrovirals (e.g. nelnavir)
Antibiotics
Psychotropics (e.g. SSRIs)
Herbals, articial sweeteners, other
Usual and opportunistic infections
Viral
Bacterial
Protozoal
Mycobacterial
HIV
Neoplasms
Lymphoma
Kaposis sarcoma
Multiple concurrent infections may be found.
No discernable cause will be found in up to 50%.
Essential Information for the Evaluation of Diarrhea
CD4 count (if <100, opportunistic infections are likely)
82
Medications (antiretrovirals, antibiotics, herbals)

Sexual practices (? anal intercourse)
Epidemiology (travel, water source)
Acuity, severity, systemic symptoms
Pattern (small bowel vs. large bowel)
Patterns of Diarrhea
Small Bowel (SB)
Large volume
Mid abdominal pain
No blood/pus in stool
Large Bowel (LB)

Small Volume
Lower abdominal pain
Blood/pus in stool
Differential Diagnosis of Infectious Diarrhea

Protozoal
Cryptosporidium parvum * SB
Microsporidia (Encephalitozoon intestinalis; Enterocytozoon
bieneusi)* SB
Encephalitozoon intestinalis
Enterocytozooan bieneusi
Isospora SB
Cyclospora cayetanensis SB
Giardia intestinalis SB
Entamoeba histolytica LB
Blastocystis hominis SB
Strongyloides stercoralis SB
Viral
Picobirnavirus SB
Adenovirus SB
Calicivirus SB
CMV * LB
HSV LB
HIV enteropathy SB
Rotavirus SB
Norwalk SB
Astrovirus SB
Bacterial
Shigella * LB
Campylobacter * SB
Salmonella species SB
83
Clostridium difcile * LB
Enteroaggregative E. coli
Pleisiomonas/shigelloides
Aeromonas
Mycobacterium avium complex * SB
Mycobacterium tuberculosis SB
Yersinia enterocolitica SB
Fungal
Histoplasma capsulatum
* - Common
SB - small bowel pattern
LB large bowel pattern
Diagnosis
Stool Analysis
Occult blood
Leukocytes
Cultures for bacterial pathogens
C. difcile toxin assay
Ova and parasites examination (3 samples)
Modied acid fast stain (Cryptosporidia, Isospora,
Cyclospora)
Modied trichrome stain (microsporidia)
Direct uorescent antibody (DFA), ELISA antigen tests
(Cryptosporidium, Giardia)
Fiberoptic sigmoidoscopy with biopsies, and if negative
Colonoscopy with biopsies
Upper GI endoscopy with biopsies, possibly enteroscopy
Procedures for Stool Specimens
Alert laboratory that specimens are for HIV-associated diarrhea.
Use carrier media and preservatives (e.g. Meridian ParaPak
Enteric Plus for cultures and Meridian ParaPak - PVA and
10% formalin- for parasites) unless the stool samples can be
delivered to the laboratory within 1 hour of collection.
Three liquid stool samples collected at least 1 day apart for O&P
examination.
A single liquid stool specimen may be sufcient for diagnosis of
Cryptosporidium or microsporidia because the organisms are
usually present in large numbers.
84
Approaches to managing diarrhea
Consider medications as a cause
If mild, no systemic symptoms, no rectal bleeding, do stool studies
only,
If a specic treatable cause is found, give treatment
If no cause is found,
Non-specic treatment or
Empiric trial of quinolone and metronidazole
If severe, with systemic symptoms and/or rectal bleeding, do stool
studies and
Colonoscopy with biopsies rst for large bowel pattern
Upper endoscopy with biopsies rst for small bowel pattern
Treatment of Common Causes of Diarrhea in HIV
Immune reconstitution with HAART when possible
Non-specic treatment
Diphenoxylate with atropine, Imodium, paregoric, deodorized
tincture of opium.
Octreotide 50-200 mcg SC/IV 1 to 3 times a day up to a
maximum of 1500 mcg/day.
Cryptosporidium, microsporidia, Isospora, Giardia, E.
histolytics, Blastocystis hominis, CMV, Salmonella, Shigella,
Campylobacter, E. coli, Yersinia- See Appendix 1
Trimethoprim-sulfamethoxazole 1 DS tablet 2 times daily for 7
days, then 1 DS tablet 3 times a week chronically
ANORECTAL SYNDROMES
Perirectal abscess
Anal stula
Gonorrhea
Herpes simplex virus
Cytomegalovirus
Chlamydia
Tuberculosis
Histoplasmosis
Lymphoma
Squamous cell dysplasia/cancer
85
Evaluation
Examination of perirectal skin and regional (inguinal) lymph
nodes.
Digital rectal exam for masses, tenderness.
Anoscopy and sigmoidoscopy with biopsies (anesthesia if
painful).
Pap smear of anal canal for dysplasia/cancer.
Gram stain of stool for leukocytes, gonorrhea.
Cultures of stool for bacterial pathogens.
Tzanck prep/culture for HSV of perirectal lesions.
RPR
Complement xation or microimmunouorescence serology for
Chlamydia trachomatis.
Treatment
Neisseria, Gonorrhea, HSV, CMV, tuberculosis, histoplasmosisSee Appendix 1
Doxycycline 100 mg 2 times a day for 21 days
Erythromycin 500 mg 4 times a day for 21 days
GASTROINTESTINAL BLEEDING
Most bleeding in HIV-infected patients is from the same causes as
in non-immunocompromised patients
Erosive esophagitis, Mallory-Weiss tear, esophageal and/or
gastric varices, peptic ulcer disease
Causes more common in HIV-infected patients include
Cytomegalovirus enteritis
Kaposis sarcoma
Lymphoma
ABDOMINAL PAIN
Usual causes as in non-immunocompromised patients
Peptic ulcer disease, gallstone disease, pancreatitis,
appendicitis, diverticulitis, bowel obstruction.
Causes more common in HIV-infected patients include
Acalculous cholecystitis
86
Cholangiopathy and/or papillary stenosis.

Pancreatitis due to medications, infections, tumors.
CMV enteritis (ulceration, perforation).
Intestinal lymphoma (obstruction, perforation).
Kaposis sarcoma (intussusception).
Patterns of Abdominal Pain

Acute, severe
Upper abdominal/RUQ, with abnormal LFTs and/or abnormal
lipase/amylase.
Acalculous cholecystitis.
Cholangiopathy /papillary stenosis.
Acute pancreatitis.
Mid abdominal or generalized, constant
Acute pancreatitis.
Perforation (especially due to CMV).
Mid abdominal or generalized, cramping
Bowel obstruction (especially due to tumor).
Chronic or subacute, with diarrhea and/or mild nausea/vomiting
Gastritis and/or enteritis due to opportunistic infections.
Tumor, especially lymphoma.
Approach to Abdominal Pain
Determine pattern, severity, and acuity of pain, as well as
associated symptoms (fever, vomiting, diarrhea, bleeding, etc.).
Obtain liver chemistries, amylase, lipase, CBC.
Obtain early sonography and/or abdominal CT.
Obtain early surgical consultation for history or ndings
suspicious for bowel obstruction, bowel perforation, acute
cholecystitis.
BILIARY/PANCREATIC SYNDROMES
Acalculous cholecystitis
Associated with opportunistic infections such as
Cryptosporidium, microsporidia, Isospora, CMV, Candida.
Diagnosis
Sonography: edema gallbladder wall, pericholecystic uid.
HIDA scan: failure to ll gallbladder.
Often associated with cholangiopathy/papillary stenosis.
Treatment: cholecystectomy.
87
Cholangiopathy/papillary stenosis
Associated with the same opportunistic infections as acalculous
cholecystitis.
Irregular narrowing and dilation of intra- and extra-hepatic bile
ducts, stenosis of ampulla of Vater.
Clinical presentation: upper abdominal pain, abnormal LFTs.
Alkaline phosphatase, GGT may be very high, but overt
jaundice is unusual.
Diagnosis
ERCP with biopsies
MRCP
Treatment
Endoscopic papillotomy may relieve pain if papillary
stenosis is present, but does not affect LFTs or prognosis.
Acute pancreatitis
Differential diagnosis
Medications ddI
NRTI- didanosine (increased risk with dose >12.5/mg/kg/
day), d4t,ddC
Pentamidine (increased risk with cumulative dose > 1 gm)
TMP-SMX
Infections
CMV, HSV, Cryptococcus, Candida, Toxoplasma,
Cryptosporidium
Neoplasms
Lymphoma
Kaposis sacrcoma
Cholangiopathy with papillary stenosis
88
NEUROLOGICAL COMPLICATIONS
RICK DASHEIFF, MD
89
DEMENTIA
Dementia is the progressive loss of cognitive functions

irrespective of etiology. Pseudo-dementia from depression or
drugs should be considered.
Causes: Alzheimers disease, subdural hematoma,
hydrocephalus, progressive multifocal leukoencephalopathy,
toxoplasmosis, cryptococcosis, HSV/CMV/VZV encephalitis, TB
meningitis, neurosyphilis, lymphoma.
HIV encephalopathy (AIDS dementia complex) requires a
diagnosis of HIV infection and dementia without another etiology.
Prevalence may be as high as 25%. Prognosis is poor.
Diagnosis
Cognitive decline, memory and cognitive testing (Mini-Mental
Status Exam, or a formal battery of neuropsychological tests).
Brain imaging, EEG, and CSF analysis non specic.
Treatment
Antiretrovirals may help. NMDA antagonist agents such as
memantine or riluzole may help HIV dementia.
ENCEPHALITIS
Acute HIV infection may cause aseptic meningitis,

encephalopathy, or myelopathy. A rare multiple sclerosis-like
illness may occur. HIV encephalitis may result in altered and
progressive changes in mental status, changes in vision, motor
weakness or spasticity, incoordination, or seizures.
Toxoplasmosis, tuberculosis, cryptococcosis, herpes,
encephalitis, syphilis, acute viral infections, systemic collagen
vascular diseases, cerebral vasculitis, vitamin B12 deciency,
prion disease.
Toxoplasmosis is a common CNS infection in AIDS. Serum
Toxoplasma IgG is usually positive, brain CT or MRI often reveals
edema and absess-like lesions. CSF may show mononuclear
pleocytosis and elevated protein but may be normal. CSF PCR
for T. gondii DNA has shown reasonable specicity but poor
sensitivity.
90
Management
HIV encephalitis should be treated with HAART. For other
organism-specic treatment, see Appendix, Therapy for frequent
infectious diseases
ERGOTISM
Acute ergotism with vasospasm and ischemia of the extremities,

hypotension, and death, is rare but becoming more frequent with
the concurrent administration of ergotamine preparations (usually
for headache) and ritonavir.
Ergotamine is metabolized by hepatic cytochrome P450
isoenzyme 3A4. Ritonavir, a potent 3A4 inhibitor, may
signicantly decrease the metabolism of ergotamine resulting
in a toxic ergotamine concentration after a single oral dose.
The concomitant use of drgotamine and ritonavir is absolutely
contraindicted.
Cerebral ergotism is vasospasm of the supra-aortic vessels,
resulting in a stroke syndrome and is very rare. It is associated
with chronic abuse, overdose, or individual oversensitivity to
ergots. Cases are now appearing in patients taking normal or low
doses in combination with ritonavir.
The concomitant use of ergotamine and ritonavir is
absolutely contraindicated.
Diagnosis
Brain CT or MRI, conventional or MR angiography. Rule out
other causes with routine laboratory tests, protein C, S, activated
protein C resistance, antithrombin III, homocysteine, brinogen,
and lipoprotein-A.
Treatment
Acute stroke from ergotism should be managed in an ICU setting
by a stroke expert. Intravenous nitroglycerin, which may be
helpful in counteracting vasospasm, may precipitate hypotension
and exacerbate the stroke. Combining hemodilution,
hypertension, and hypervolemia may help.
HEADACHE
Most HIV-infected patients with headache may be treated with

analgesics and followed. Patients with focal neurological signs,
altered mental status, seizure, or CD4 200/ml are at high risk of
an intercranial lesion and warrant a screening head CT.
91
Intracranial Lesions in AIDS
Protozoa
Toxoplasma gondii
Fungi
Cryptococcus neoformans
Histoplasma capsulatum
Candida sp.
Aspergillus fumigatus
Viruses
JC virus (PML)
Cytomegalovirus
Varicella-zoster
Herpes simplex
HIV encephalopathy
Bacteria
Mycobacterium tuberculosis
Bartonella henselae
Rhodococcus
Nocardia asteroides
Neoplasms
Primary CNS lymphoma

Metastatic lymphoma
Kaposis sarcoma
LYMPHOMA
Non-Hodgkins lymphoma is the second most common

malignancy in AIDS. Incidence of primary CNS lymphoma in
AIDS is 3600 times that of the general population.
Usually aggressive, high grade, B-cell phenotype. Most common
histologic subtype is large cell immunoblastic followed by small,
non-cleaved cell. All EBV related. Usually conned to the CNS in
patients with CD4 count <50/L and prior history of opportunistic
infections.
Symptoms
Insidious headache, confusion, lethargy, seizures, and focal
neurological decits.
Diagnosis
CT with contrast shows single or multicentric hypodense lesions
MRI shows variable signal that may enhance with contrast
(either homogenous or ring-like ), with surrounding edema. May
be necrosis and mass effect. Usually located in the cerebrum,
basal ganglia, cerebellum, and occasionally the brainstem.
92
Primarily toxoplasmosis. Other considerations PML, TB and
cryptococcoma.
Routine CSF studies non-specic for lymphoma; CSF cytology
rarely helpful; however, CSF PCR for EBV may be useful. CSF
studies to consider alternative diagnoses.
. 201Thallium- SPECT scanning may also be useful. A positive
scan is suggestive of lymphoma, while a negative scan suggests
another diagnosis (toxoplasmosis, tuberculosis, etc). Denitive
diagnosis requires stereotactic brain biopsy
Chemotherapy s ineffective. Whole brain radiation used, but
median survival in treated patients has only been ~1-3 months
in pre-HAART era. Anecdotal reports of patients responding to
HAART y alone.
Corticosteroids may be used if edema or threat of herniation.
Lymphoma may respond to corticosteroids alone, which may
obscure diagnosis.
MENINGITIS
Aseptic meningitis
Associated with HIV in absence of other etiologies. Acute or
chronic headache, neck stiffness, blurred vision, photophobin,
nausea, altered mental status.
Diagnosis
CSF mononuclear pleocytosis, mild protein elevation and normal
or minimally decreased glucose. Brain imaging required to
exclude other diagnoses. Serologic tests and PCR of CSF used
to identify specic viruses.
Management
Supportive care, analgesics and close follow up generally sufce.
BACTERIAL MENINGITIS
Rapid diagnosis and treatment needed as patients can progress

to coma and death within hours. Because the spectrum of
potential organisms is so large, CSF should always be obtained
for analysis and culture unlessneurologic exam reveals focal
signs or brain imaging a mass lesion.
93
TUBERCULOUS MENINGITIS
CNS TB and via hematogenous dissemination has a very high

mortality (79%) in HIV. TB meningitis is usually due to rupture of
a previous tuberculous focus from the brain into the subarachnoid
space.
Fever and meningeal signs (80%), headache (60%), altered
mental status (75%), cranial nerve palsies (25%) especially 3rd
cranial nerve. Focal decits rare.
Diagnosis
CSF lymphocytosis, high protein, low glucose. CSF-AFB stain
10-24% positive,. Culture is standard. Elevated CSF adenosine
deaminase may be helpful. TB-PCR (may be helpful if positive)
but only approved for sputum.
Abnormal CXR (65%).
Predominantly basal involvement in the region of pons, optic
nerve and chiasm detectable by brain CT scan (65%) and by
MRI scan (85%). Tuberculomas associated with TB meningitis
detected in 28%-65% on MRI. Tuberculous brain abscess
occurs in up to 25% in HIV patients, tend to be larger than
tuberculomas, usually solitary, and have more accelerated
course. Cerebral infarctions and hydrocephalus also common.
Treatment
4 TB drugs (see section on Pulmonary TB) without delay and
often started presumptively a denitive diagnosis. Treatment
durations minimum 9 months.
Dexamethasone for patients with signicant confusion or edema.
FUNGAL MENINGITIS
Signs and symptoms subacute to chronic, with a resulting long

delay in diagnosis. Cryptococcal meningitis is representative.
Because spectrum of potential organisms so large, spinal uid
should always be obtained for analysis and culture unless
neurologic exam reveals focal signs or brain imaging reveals
mass lesion.
CRYPTOCOCCAL MENINGITIS
Cryptococcus neoformans, an encapsulated yeast, is leading

cause of CNS infection (6-10%) in AIDS with CD4 usually
94
<100/L. Usually newly acquired cryptococcal infection.
Subacute f headache, +/-fever. Less common: nausea, vomiting,
photophobia, and altered sensorium. Focal complaints rare
and meningismus uncommon. Skin lesions may resemble
molluscum contagiosum.
Diagnosis
Normal CSF prole may occur. Measure opening pressure.
India ink test no longer used Cryptococcal antigen (CRAG)
on serum or CSF key to diagnosis. CSF, blood, urine, and skin
lesions should be cultered for fungus.
Brain CT or MRI often normal but may show meningeal
enhancement or rarely cryptococcomas. Cryptococcomas
(gelatinous pseudocysts) often appear in basal ganglia, are
hypodense on CT, hyperintense on MRI-T2 images, and do not
enhance.
Treatment
- see Appendix, Therapy for frequent infectious diseases.
Management of elevated ICP differs depending on whether there
is mass effect generalized brain swelling or hydrocephalus.
Enlist Neurology or Neurosurgery when considering serial LPs;
acetazolamide; shunt.
MONONEURITIS MULTIPLEX
Multifocal, asymmetric, cranial or peripheral nerve lesions,

including facial or laryngeal palsy, wrist or foot drop.
Course depends on stage of HIV: in early HIV, it is limited to one
or few nerves and resolves spontaneously without treatment.
In advanced disease, neuropathy may progress rapidly to
quadriparesis.
May improve on IV ganciclovir, suggesting CMV role.
MYELOPATHY
AIDS-associated myelopathy has 20 - 55% prevalence and is a

diagnosis of exclusion.
Clinical symptoms usually develop late, with slowly progressive
weakness of the legs, loss of proprioception and vibration,
impotence, and urinary frequency and urgency. Incoordination of
95
gait progresses, and combined with weakness, leads to a spastic
paraparesis and loss of sphincter control.
Diagnosis
Neurologic exam looking for corticospinal tract and posterior
column dysfunction, MRI imaging of the cord, CSF analysis, and
serum forCMV, HTLV-I toxoplasmosis, B12, neurological folate,
and methylmalonic acid. CSF in CMV myelopathy shows PMN
pleocytosis.
Management
No specic treatment, and antiretroviral drugs have no proven
efcacy in prevention or therapy. Patients have normal serum
B12 levels (by denition), and supplementation with vitamin
B12 is not helpful. However, experimental ndings of abnormal
transmethylation suggest a trial of methyl group donors such as
SAM or L-methionine.
Supportive care, preferably on a Spinal Cord Injury Unit, should
address the physical disabilities affecting activities of daily living
Spasticity may be helped with baclofen.
MYOPATHY
Muscle disease can present at any stage of HIV infection,

even as the rst manifestation. HIV polymyositis and AZTinduced myopathy represent a spectrum of inammatory
and mitochondrial pathologies. Whether this is one or more
diseases is uncertain, and poses a risk of unnecessarily using
corticosteroids rather than just discontinuing AZT.
Chronic and slowly progressive proximal weakness with elevated
CPK with or without muscle tenderness. EMG testing may be
conrmatory but is not necessary.
Diagnosis
Muscle biopsy is denitive. Immunohistology for MHC class I
antigen and the histochemical reaction for cytochrome C oxidase
differentiate HIV polymyositis from AZT myopathy.
96
Myopathy
Criteria
HIV-associated myopathy
meets criteria for polymyositis or

acquired nemaline myopathy
AZT myopathy
reversible mitochondrial myopathy
HIV-wasting syndrome
grouped with AIDS-associated

cachexias
Inammatory myopathy
opportunistic infections
(toxoplasmosis, CMV, Microsporidia,
Cryptococcus,
MAC, S. aureus), tumoral inltrations
Vascular myopathy
vasculitic processes, iron pigment

deposits
Treatment
Depends on etiology. Discontinue AZT and weakness and CPK
followed for signs of improvement. Otherwise, prednisone (60
mg/day) may be tried.
Neuropathy
One-third of patients with AIDS may have distal sensory
polyneuropathy characterized by pain, numbness, and burning,
primarily in the soles and dorsa of the feet. History of >6 weeks
of burning pain or uncomfortable sensations in both feet and/or
legs, diminished ankle jerks, reduced sensations of vibration,
pain, or temperature in the legs.
Neuropathy may be toxic effect of ddI or ddC therapy or
a direct effect of HIV . Which are indistinguishable. The
clinical severity, and absence of effective treatment have
led to its characterization as one of the most devastating
and unresponsive complications of HIV disease. Consider
diabetes, restless legs syndrome, myelopathy, B12 or pyridoxine
deciency.
Nerve conduction studies and EMG generally unhelpful in
evaluating pure sensory neuropathy. Weakness in the foot or leg
could a motor component to the neuropathy which should then
be studied.
Management
Tends to be unsatisfactory, requires a trial-and-error approach
97
to medication. Approaches which have not been encouraging:
mexiletine, Peptide T, capsaicin cream, acupuncture, behavioral
therapy, tricyclics (e.g. amitriptyline), tramadol, and AEDs like
carbamazepine and phenytoin. Beware drug-drug interactions
(see AED table).
Lamotrigine has been was well-tolerated and effective in patients
receiving neurotoxic antiretroviral therapy. Start low (25mg QD)
and advance slowly (25mg qweek) up to 200mg bid. Gabapentin
300mg tid, and advancing rapidly to 900mg tid may also be
helpful.
Opioids not very effective for neuropathic pain. However, with
close monitoring and limit setting, they have a role in intractable
neuropathic pain. Lidocaine patch, for localized pain, is gaining
acceptance.
NEUROSYPHILIS
HIV patients can have all stages of syphilis.

Neurological Manifestations of Syphilis
Secondary Syphilis
Aseptic meningitis syndrome
Meningovascular
Hemiplegia or hemiparesis
Seizures
Aphasia
Optic neuritis
General Paresis
Dementia
Hyperactive reexes
Slurred speech
Argyll-Robertson pupils
Optic atrophy
Tremors
Tabes dorsalis
Shooting pains
Ataxia
Argyll-Robertson pupils
Impotence
Fecal and bladder incontinence
Cranial nerves 2-7 involvement
98
Diagnosis
Serum RPR/MHT-TP, CSF VDRL, brain imaging, EEG. Testing
for immunoglobulins or treponemal antigens, and cultures for
treponemes are unhelpful.
CDC Recommendations for Lumbar Puncture in
Patients Possible Syphilis
Signs or symptoms consistent with neurosyphilis
Late latent syphilis (positive RPR)
Clinical or serologic treatment failure for any stage of syphilis
Inability to treat with penicillin
HIV infection
Treatment
Early syphilis in HIV may fail therapy with penicillin G, and
neurosyphilis can develop. High-dose penicillin regimen
recommended for neurosyphilis may not be consistently effective
in HIV but is treatment of choice. See Appendix, Therapy for
frequent infectious diseases
PARKINSONISM
Movement disorders (e.g. action tremor, Parkinsonism) reported

in AIDS and AIDS dementia complex. Some had opportunistic
infection or previous exposure to neuroleptic drugs. Rarely,
Parkinsonism can be initial manifestation of HIV.
Manifestations of HIV associated induced Parkinsonism

Typical PD signs & symptoms
Decreased eye blinking

Cogwheeling
Bradykinesia - slowness on motor
tasks
Resting tremor
Decreased arm swing
Retropulsion
99
Manifestations of HIV associated induced Parkinsonism
Atypical PD signs & symptoms
Action tremor
Dystonia
Dementia
Up gaze paresis
Hallucinations
Balance problem
Autonomic dysfunction
Dysarthria
Hyperreexia
Diagnosis
History and neurologic exam.
Brain imaging (MRI) should always be considered for HIV
patients to exclude an opportunistic infection. TSH, calcium,
copper, ceruloplasmin, ANA, CSF for cells, protein, glucose,
EBV-PCR, CMV-PCR and cultures for bacteria and fungi. Early
detection of HIV in patients who present with Parkinsonism is
importan, as. HAART may completely reverse it. Carbidopa/
levodopa or pramipexole help the tremor and rigidity.
POLYRADICULONEUROPATHY
Symptoms resemble Guillian-Barre syndrome CGBS, with

progressive ascending weakness in legs, loss of reexes and
urinary retention. Sensory loss variable. When severe, complete
paralysis requires ventilatory and autonomic support. May have
back pain.
Increased incidence in patients with for CMV retinitis, colitis, or
esophagitis.
Elevated CSF protein >100 (always do repeated LPs to
document course and conrm diagnosis, especially if 1st CSF
protein < 100). Unlike GBS CSF pleocytosis (PNMs) may
be present. CSF CMV-PCR usually positive. CMV serology
not helpful. MRI of spinal cord to rule-out abscess or tumor
encroachment.
Management
Treat as if CMV colitis (see Appendix, Therapy for frequent
infectious diseases).
If refractory, steroids, plasmapheresis, or IVIG may be tried.
Prognosis poor. Anecdotal reports of improvement on HAART.
100
PREGNANCY
HIV infection of a child in utero or at delivery puts the infant

at risk for neurological damage (HIV encephalopathy, CNS
opportunistic infection) and retarded neurodevelopment. This is
independent of, and additive to, the mothers use of hard drugs or
alcohol.
Prevention
Routine HAART perinatal to HIV-infected mothers.
Treatment
Early and aggressive HAART to HIV- infected infants.
PROGRESSIVELY MULTIFOCAL LEUKOENCEPHALOPATHY (PML)
HIV-associated PML has median survival 1-6 months. 8% have

a more benign course, with remission and prolonged survival, or
even spontaneous recovery.
Progressively altered mental status, speech and visual
impairment, gait difculty, hemiparesis, and limb incoordination.
Diagnosis
Exclude stroke, infection, tumor, AIDS dementia complex and
CMV encephalitis. Brain CT or MRI, with/ without contrast:
Multifocal white matter signed on T2; poor enhancement on T1.
CSF analysis to rule out OIs is mandatory, and JC virus PCR of
CSF may be helpful. Rarely, a denitive diagnosis depends on
brain biopsy.
Management
No effective treatment. HAART, cidofovir, steroids may help.
SEIZURES
Single non-focal convulsion (grand mal seizure) may be

isolated event with only 20% chance of recurrence. However,
assume that a seizure in a patient with known HIV has epilepsy.
Initial manifestation of HIV/AIDS may be a seizure.
Work up: EEG, brain imaging, CSF analysis.
101
Management
Antiepileptic drug (AED) may start immediately (see AED table).
AEDs do not produce false-negative EEG.
Work up: Finds drug toxicity or metabolic etiology in up to 50%,
in which case AED may be stopped if the EEG is negative.
Antiepileptic Drugs (AEDs)
Consider therapy-compromising drug-drug and drug-disease
interactions. Ideal drugs do not affect viral replication, have
limited protein binding and minimal effects on the cytochrome
P450 system.
Phenytoin, carba mazepine, and primedone are P450 inducers
which increase the metabolism of other drugs.
Ritonavir is a potent inhibitor of cytochrome P450 enzyme
CYP3A4. Concurrent use of such AEDs as carbamazepine or
phenytoin with ritonavir or other P450 enzyme inhibitors can
induce toxicity of the
Antiepileptic Drugs
Drug
Cytochrome
P450 inducer
Treatment choice
Gabapentin
Neurontin
No
High
Lamotrigine
Lamictal
No
High
Topiramate
Topamax
No
High
Levetiracetam
Keppra
No
high
Phenytoin
Dilantin
yes, strong
low, but available i.v.

for SE*as fosphenytoin
Primidone
Mysoline
yes, strong
low
Carbamazepine
Tegretol/
Carbatrol
yes, strong
low
Oxcarbazepine
Trileptal
yes
low
Valproic acid
Depakote
no
relatively
contraindicated
(induces HIV
replication)
*SE = status epilepticus
102
TRANSIENT NEUROLOGIC DEFICITS
A brief episode of loss of vision, weakness, numbnessin

coordination, aphasia or loss of consciousness is frequently
called a TIA (transient ischemic attack). However, a vascular
cause is often not evident, in which case the more generic term
TND (transient neurologic decit) is appropriate.
Seizures are almost never the cause, nor is simple syncope,
migraine or multiple sclerosis. In fact, no etiology is generally
found, and stress related illness remains possible.
TND may occur in AIDS dementia complex, or in any HIV
infected patient.
Management
Treatment is directed at a specic diagnosis. Repeated episodes,
especially if symptoms differ between attacks, and brain imaging
negative, should be followed up by Neurology and Psychiatry.
103
104
105
106
107
108
ENDOCRINOLOGIC & METABOLIC COMPLICATIONS

ASRA KERMANI, MD
109

SERUM LIPIDS
Signicant declines in total, LDL-, and HDL-cholesterol occur

after HIV seroconversion and are present prior to the initiation of
HAART.
HAART may restore total and LDL- cholesterol values to normal
which correlates with overall improved health on HAART, but
may increase potential risk for cardiovascular disease.
Lipodystrophy
Lipodystrophy is a consequence of HAART therapy characterized
by abnormal fat deposition in the abdomen, breasts, and nape
of the neck (buffalo hump) with loss of fat in the gluteal region,
legs, arms, and face.
Lab elevated triglycerides, raised LDL- and low HDL-cholesterol.
Frequently insulin resistant and may progress to type 2 diabetes.
Cause unknown: medications implicated include PIs and NRTIs.
GLYCEMIA
Impaired glucose tolerance or type 2 diabetes may be

precipitated in patients with lipodystrophy. Insulin resistance may
occur with PIs. Treatment includes substituting the PI with NNRTI
or NRTI. Insulin sensitizing agents (metformin, thiazolidinediones)
may help.
Hypoglycemia occurs in 4-33% of patients treated with
pentamidine.
GONADAL FUNCTION
Male hypogonadism is diagnosed by low testosterone(T)

levels. Free T levels may be more reliable than total T. Primary
hypogonadism, with low T levels and increased LH occurs in
approximately half of men with AIDS. Others may have features
of secondary hypogonadism, with low T and inappropriately
normal or low LH. Up to 25% of women with HIV develop
amenorrhea, decreased muscle mass or androgen deciency.
Low-dose androgen replacement may help.
Clinical features: fatigue, reduced strength, wasting, impaired
sexual function.
Treatment
Replacement testosterone therapy.
110

Testosterone 200 mg IM every 10-14 days
Testosterone patch, 5 mg every 24 hours
ADRENAL DISEASE
Clinically evident adrenal insufciency is uncommon.
Frequent causes
Opportunistic infection: tuberculosis, MAC, CMV,
histoplasmosis, HIV adrenalitis
Consequence of treatment with megestrol, ketoconazole, or
rifampin
Findings vary: fatigue, fever, hyponatremia, hyperkalemia,
orthostatic hypotension, mild metabolic acidosis, peripheral
eosinophilia.
Diagnosis
Cosyntropin (Cortrosyn) stimulation test.
Draw baseline serum cortisol, administer 250 mcg of cosyntropin
IV, and recheck serum cortisol at 30 and 60 minutes. Serum
cortisol less than 18 mcg /dL at either 30 or 60 minutes is
diagnostic.
Treatment
Acute adrenal insufciency: hydrocortisone 100 mg IV every 6-8
hours or dexamethasone 4 mg IV every 12 hours.
Chronic adrenal insufciency oral therapy:
Hydrocortisone 15-20 mg morning, 5-10 mg afternoon; OR
prednisone 5-10 mg orally daily; OR dexamethasone 0.250.75 mg daily
Fludrocortisone is often required, 0.05-0.2 mg daily
Thyroid dysfunction
Hypothyroidism may occur during antiretroviral therapy.
Infectious thyroiditis may be caused by PCP, fungi, TB and other
pathogens. It resolves as the underlying infection is eradicated.
Most patients are asymptomatic, but some have painful goiter,
transient thyrotoxicosis or hypothyroidism.
111

Hypopituitarism
Panhypopituitarism is rare in HIV, but has occured with
toxoplasmosis.
Calcium
Hypocalcemia is common in HIV. Frequently a side effect of
foscarnet or amphotericin B, CMV infection, secondary to renal
Mg loss, resulting in impaired PTH release and hence low ionized
calcium levels.
Hypercalcemia may occur in HIV-related lymphoma.
Hyponatremia
Very common in HIV. Causes include volume depletion, adrenal
insufciency, drugs, and especially SIADH.
112

Drug interactions
Medication
Interaction
Effect
HMG CoA reductase

inhibitors
PI and NRTIs
Myopathy,
rhabdomyolysis (least
with pravastatin)
Dexamethasone
Indinavir, saquinavir
Reduced concentrations
of indinavir, saquinavir
Itraconazole
Increased blood
glucose, myopathy
Rifampin, rifabutin
Reduced
dexamethasone
effectiveness
Ritonavir
Increased
dexamethasone
concentrations, with
increased glucocorticoid
side effects
Itraconazole
Increased blood
glucose, myopathy
Rifampin, rifabutin
Reduced hydrocortisone
effectiveness
Fludrocortisone
Rifampin
Reduced udrocortisone
effectiveness
Levothyroxine
Ritonavir
Reduced levothyroxine
efcacy; monitor TFTs
closely and adjust
thyroid dose
Hydrocortisone
113
114
RENAL DISORDERS
JAMSHID AMANZADEH, MD
115
RENAL DISORDERS
HIV ASSOCIATED NEPHROPATHY (HIVAN)
Occurring almost exclusively in seropositive African American

patients, HIVAN occasionally affects Hispanics and very rarely, if
ever Caucasians.
Most HIVAN patients have experienced an AIDS dening
condition or a CD4+ cell count less than 250cells/mm3.
Approximately 50% of HIVAN, usually patients have history of
intravenous drug use.
Most patients present with proteinuria and reduced renal
function. Proteinuria can range from modest amount (0.5 to 1.5 g
protein/24 hours) to nephrotic levels.
Normal or low systolic blood pressure is common.
The clinical suspicion is only predictive of the biopsy diagnosis in
55% to 60% of patients. Thus, a renal biopsy is usually required
to distinguish HIVAN, usually focal segmental glomerulosclerosis
(FSGS), from other forms of renal disease in HIV-seropositive
patients.
ACUTE RENAL FAILURE SYNDROMES
Like ARF in other patients, etiology of ARF in HIV patients can be

categorized into pre-renal, intrinsic, and post renal. Prerenal can
be secondary to GI loss, poor intake (anorexia, disabling CNS
disease), hypotension or third space sequestration (as in massive
proteinuria and hypoalbuminemia).
ATN is the most common form of ARF syndrome in these patients
and is commonly related to the administration of nephrotoxic
or crystalluric agents in a volume depleted patient. Plasmacytic
interstitial nephritis is a rare but treatable cause of ARF in HIV
patients. This entity presents with proteinuria and azotemia and
responds to steroid therapy. This underlines the signicance of
kidney biopsy in making diagnosis of treatable causes of ARF in
HIV patients.
HIV-associated microangiopathy syndromes (HUS-TTP) also can
cause ARF. They are thought to occur because of endothelial cell
dysfunction partially mediated by HIV proteins and in contrast
to HIVAN, are more common in whites. High-level proteinuria is
uncommon.
116
RENAL DISORDERS
HIV-associated glomerulopathies
In addition to FSGS, other glomerulopathies have been
described in HIV patients. The most common immune complex
mediated glomerulonephritis among HIV-infected patients is
membranoproliferative GN, particularly among intravenous drug
users with HCV coinfection. HIV associated IgA nephropathy can
be seen in whites and Hispanics with HIV, but is less common in
African Americans.
Presence of tubuloreticular inclusions in glomerular cells is a
differentiating feature from idiopathic IgA nephropathy.
Coincidental Renal disorders
A vast variety of electrolyte abnormalities can be seen in HIV
patients. These are in general related to volume depletion, GI
loss or secondary to adverse consequences of therapeutic
agents in the management of retroviral, bacterial, and
opportunistic infections.
Hyponatremia (primarily due to volume depletion) is the most
common electrolyte abnormality and irrespective of etiology is
associated with an increased morbidity and mortality.
Renal tubular dysfunction and Fanconi syndrome secondary to
medication (e.g. ddI, tenofovir, cidofovir, adefovir) have been
reported. Also type B lactic acidosis secondary to AZT- induced
mitochondrial myopathy has been described.
Opportunistic infections such as TB, CMV, and fungal infections,
and complications such as lymphoma and Kaposi sarcoma, are
associated with structural abnormalities, renal insufciency and
acute renal failure.
117
118
119
120
RHEUMATOLOGIC COMPLICATIONS
SALAHUDDIN KAZI, MD
121
Clinical Manifestations
Monoarthritis: Septic arthritis secondary to Staphylococcus
aureus is the dominant cause of acute monoarthritis accounting
for over 70% of cases of nongonococcal septic arthritis,
presenting as an acutely inamed joint with systemic symptoms.
Sometimes multiple joints are involved. Pyogenic sacroiliitis in
intravenous drug users, usually caused by S. aureus, presents
with fever, back pain, and exquisite local tenderness. With
advanced CD4 depletion, fungal and mycobacterial septic
arthritis occur. The arthritis is generally more indolent with
subtle inammation. Juxta-articular osteomyelitis is a common
complication. Pyomyositis typically presents with acute pain in
the thigh or other large muscle with woody induration, swelling,
and erythema. Soft-tissue symptoms, such as arthralgias, and
nonspecic arthritidies have been attributed to initiation or
change in antiretroviral therapy. Crystal arthritis may occur.
Reiters Syndrome: onset is usually with urethritis or enteritis,
followed by skin and joint disease. Uveitis and sacroiliitis are
rare. Cutaneous disease is very prominent: keratoderma
blenorrhagicum, a scattered papulosquamous eruption that
occurs on the palms, soles and penis, is common and may
progress into a generalized eruption indistinguishable from
pustular psoriasis. Oligoarticular arthritis involving the knee or
ankle and multidigit dactylitis commonly occur.
Sicca Syndrome (DILS: Diffuse Inltrative Lymphocytosis
Syndrome): a Sjgrens syndrome-like disorder caused by
CD8 inltration with bilateral parotid gland enlargement (often
massive), sicca (often minor), and prominent extraglandular
sites of lymphocytic inltration (lung, muscle, lymph nodes).
CD8 inltration of the lung causes a lymphocytic interstitial
pneumonitis, which causes dyspnea and can progress to brosis.
DILS frequently occurs early in the course of HIV infection and
has been associated with delayed progression to AIDS.
Myopathy: CD8 inltration may cause a myopathy
indistinguishable from idiopathic polymyositis, with elevated
serum CPK levels, proximal muscle weakness, and occasionally
with skin lesions characteristic of dermatomyositis (heliotrope
122
rash, Gottrons papules, periungual erythema). AZT can cause
a myopathy similar to polymyositis but with less inammatory
inltrate.
Vasculitis: viral diseases have been associated with the smalland medium-sized vessel vasculitides. In HIV infection, there
are scattered reports of vasculitis. The pathogenesis is linked to
an immune complex or hypersensitivity vasculitis process. The
incidence has not changed since the advent of HAART. Vasculitis
in HIV may be associated with coinfection with agents such as
hepatitis B or C virus.
RHEUMATOLOGIC COMPLICATIONS IN HIV

Syndrome
Differential
Diagnosis
Diagnostic
Testing
Treatment
Monoarthritis
Bacterial,
crystal-induced,
mycobacterial,
fungal, aseptic,
reactive
Radiography,
synovial uid
analysis,
microbiologic
studies
Surgical
drainage,
appropriate
antimicrobial
agents
Reiters
Syndrome
Septic arthritis,
Poncets disease
(reactive
arthritis with
mycobacterial
infection)
Skin biopsy,
synovial uid
aspiration,
radiography
NSAIDs and
sulfasalazine,
topical therapy
for skin disease
Sicca Syndrome
DILS,
anticholinergic
medications
Schirmers
test, Rose
Bengal corneal
staining, parotid
scintigraphy,
minor salivary
gland biopsy
Often resolves
with HAART.
Steroids useful
for painful parotid
swelling
Myopathy
HIV-associated
polymyositis,
AZT myopathy,
cocaine use,
neuropathy,
pyomyositis
Serum CPK,
urine drug screen
for cocaine,
withdrawal of
AZT, EMG and
muscle biopsy
Prednisone 1
mg/Kg/day in
divided doses,
tapered over
three months
123
RHEUMATOLOGIC COMPLICATIONS IN HIV
Syndrome
Differential
Diagnosis
Diagnostic
Testing
Treatment
Vasculitis
Drug eruptions,
KS, disseminated
MAI, bacillary
angiomatosis,
lymphoma,
HBV and HCV
coinfection,
lymphoma,
endocarditis
Test for HBV and

HCV, biopsy,
angiography, rule
out infection and
lymphoma
Immunosuppressive therapy
with cyclophosphamide and
azathioprine is
hazardous in HIV
infection
124
MALIGNANT AND HEMATOLOGIC COMPLICATIONS

PASCHAL WILSON, MD
125
126
127
128
129
130
131
132
133
134
135
136
137
138
MENTAL HEALTH DISORDERS

ZISHAN SAMIUDDIN, MD
139

Predisposing factors include:
*High-risk behavior facilitated by a
substrate of psychiatric illness.
Emotional impact of HIV diagnosis and related decision points.
Frequent involvement of the CNS in the course of HIV infection.
CNS effects of drugs used to treat HIV and related opportunistic
infections.
Substance abuse.
Psychiatric disorders in HIV have been correlated with increased
health costs and burden of care, dysfunctional behavior, such as
unprotected intercourse, and a decrease in quality of life. These
disorders may also interfere with the patients ability to start and
adhere to HAART resulting in treatment failure.
Disorder
Prevalence
Any Mood Disorder
17.2%
Major Depression
15.3%
Dysthymia
3.4%
Anxiety Disorder
20.3%
Panic disorder
12.3%
PTSD
10.4%
GAD
2.8%
DEPRESSION
Depression in HIV is associated with perceived poor health, chronic

pain, loss of memory and concentration and non-adherence to
treatment. Symptoms include a two-week (Major Depression) or a
two-year (Dysthymia) history of pervasive anhedonia or dysphoric
mood i.e., changes in sleep and interest, excessive guilt, low energy
and concentration, changes in appetite, psychomotor agitation and
suicidal ideation.
140

Symptoms are more severe in Major Depression, less so in
Dysthymia.
Depression is not a natural consequence of HIV infection and
diagnosis is hampered by symptoms common to HIV infection
and depression. Neurovegetative symptoms may be a treatable
depressive syndrome.
Suicidal ideation demands psychiatric consult.
Best results: combination of medications and psychotherapy. No
antidepressant drug is predictably more effective than another.
These medications have no effect on CD4 counts. Medications
include selective serotonin reuptake inhibitors (SSRIs-response
rates 53-78%), atypical antidepressants, tricyclic antidepressants
(TCAs), stimulants (response rates 85-95%) and testosterone
(response rates 80%).
Effects evident in 2-6 weeks. If no response, check adherence
and reconsider the diagnosis before changing or adding drugs.
Start low, go slow because of increased sensitivity to side
effects. Titrate up every week. For instance, sertraline 25-50mg
qday for a week. Increase each week by increments of 25-50 mg
qday until taking 150 mg QD.
Drug-drug interactions with HAART are due to inhibition of cytochrome
CYP 2D6, which is a secondary pathway, after CYP450 3A4, for PIS
and NNRTIs. Perhaps side effect prole follows the rank order of
potency of inhibition: paroxetine > uoxetine > sertraline > citalopram >
escitalopram.
After initial treatment response, continue same dose for at least
4-6 months, or indenitely if depression recurs
MEDICATIONS FOR DEPRESSION
Medication
Clinical pearls
SSRIs as a class
GI, weight gain and sexual side effects. Poopout is common.
Fluoxetine
Activating side effects. Not rst line in

comorbid anxiety or insomnia
Paroxetine
Sedative properties useful in the anxious.

Drug-drug interactions.
Sertraline
.
Well-tolerated and effective.

141

MEDICATIONS FOR DEPRESSION (Contd)
Bupropion
Contraindicated in seizure patients and with

intracranial pathology. Useful for smoking
cessation and to treat sexual side effects
of SSRIs. Perhaps rst line in retarded
depression.
Venlafaxine
GI side effects common. No sexual side

effects. No weight gain. Dose dependent
increase in blood pressure.
Mirtazepine
No sexual side effects. Weight gain and

sedation. Orthostasis and dry mouth.
Medications
Clinical pearls
Tertiary TCA
Amines
Amitriptyline (useful for neuropathic pain),

Doxepin (used for sedation and pruritis) and
Imipramine. Side effects difcult to tolerate.
Do not use in LBBB or higher heart block.
Potentially fatal in overdose. Anticholinergic,
antihistaminic, alpha- adrenergic blockade.
Blood levels available.
Secondary TCA
Amines
Nortriptyline and Desipramine. Second

line agents for panic disorder. Blood levels
available. Easier to tolerate than tertiary
amines. Potentially fatal in overdose.
Trazodone
Non-addictive sedative. Orthostasis and

hangover.
Stimulants
Faster onset of action. Use in HAD and in

terminal illness. Activate and improve cortical
function. Potential for abuse.
142

PSYCHOSIS
Psychotic symptoms can be part of a primary psychiatric disorder
such as severe major depression, schizophrenia, mania, or
extremes of obsessive-compulsive disorder. They can also be
secondary to organic syndromes such as delirium, side effects
of medications, metabolic abnorrmalities, drug abuse, infections
and dementia. Psychiatric consultation is usually warranted.
Symptoms include delusions, hallucinations and disorganized
speech or behavior.
Mainstay of treatment is antipsychotic medication, which should
be chosen based on side effect prole and drug interactions. Use
lowest possible dose for the shortest time. No studies with novel
antipsychotics have been done. Most psychiatrists do not use
Clozapine because of potential for neutropenia.
MEDICATIONS FOR PSYCHOSIS
Typical High
potency
Haldol etc., high risk for extra pyramidal

symptoms and dystonias. Do not administer
pimozide with PIs risk of fatal arrhythmias.
Elevated prolactin.
Typical Low
potency
Thorazine etc., High risk for anticholinergic

side effects, postural hypotension and delirium
in advanced illness. Prolactin elevation.
Typical
Intermediate
Potency.
Molindone is well tolerated. Prolactin elevation.
Atypical
Antipsychotics
as a class
As effective and better tolerated than

conventionals. Weight gain is a side effect.
May cause prolactin elevation. Changes in lipid
and glucose metabolism, especially when used
with PIs. QT interval prolongation.
Medication
Clinical Pearls
Olanzapine
(Zyprexa, Zydis)
Start with 2.5mg QHS in naive patients;

5-10mg in experienced patients. Sedating.
Postural hypotension. Indication for acute
mania. Orally disintegrating form available
143

MEDICATIONS FOR PSYCHOSIS (Contd)
Medication
Clinical Pearls
Risperidone
(Risperdal)
Risk of EPS in higher doses. Start at 0.5- 1 or

2 mg QHS in nave vs. experienced patients.
Quetiapine
(Seroquel)
Sedating. Start at 25 mg BID-TID. Titrate up

slowly.
Depot
antipsychoticshaloperidol and
uphenazine
decanoate or
enanthate.
Weigh risk-benet ratio before use. Useful

in non-compliant patients with behavioral
dyscontrol. Less propensity to cause EPS
than oral formulations. Cover with Benadryl or
Cogentin for a few days after injection.
MANIA
Prevalence 1-2% in early HIV infection and 4-8% after the onset
of AIDS. Associated with ddI, ZDV, ethambutol, clarithromycin
and testosterone
Primary mania is likely to be a recurrence of a previous
disorder, family history and presents with classic symptoms.
Secondary mania, often seen with HIV-associated dementia
presents with irritable mood, confabulation and soft neurological
signs.
Symptoms of mania include elevated, expansive, or irritable
mood; grandiosity; increased energy and decreased need for
sleep; pressured speech; racing thoughts; impulsivity. Mania may
present with frank psychotic symptoms.
Untreated, mania can lead to self-destructive behavior, nonadherence, or unsafe sex.
Psychiatric referral strongly recommended. Depot anti psychotics
may be required, particularly in non-adherent patients, but should
be avoided if possible.
MEDICATIONS FOR MANIA
Lithium
144
Low therapeutic index; contraindicated with

renal insufciency: neurologic and renal side
effects; blood levels available;

MEDICATIONS FOR MANIA (Contd)
Anticonvulsants
Divalproex Sodium
Hepatitis, pancreatitis common
Carbamazepine
Potential for agranulocytosis; drug interactions

common; blood levels available
Lamictal
Slow titration due to risk of rash
Atypical
Antipsychotics
See above
Depot
Antipsychotics
See above
ANXIETY DISORDERS
Prevalence 25%-40%.
Anxiety disorders include mild adjustment disorders, panic
disorder, phobias, obsessive-compulsive disorder, acute and
post-traumatic stress disorder and generalized anxiety disorder
Anxiety symptoms include pervasive worry, fear, and concern
about health, death, and the uncertainty of the illness. Somatic
complaints are common: tremor, shortness of breath, palpitations,
chest pain, nausea, dizziness, choking etc., Initial insomnia and
poor concentration are common.
Underlying organic causes should be ruled out. Drug
intoxication (cocaine, stimulants etc.,) or withdrawal (alcohol,
benzodiazepines) can present as anxiety. Akathisia is a side
effect of neuroleptic medication and is often mistaken for anxiety
in patients taking neuroleptics.
Antidepressants, in particular SSRIs, and psychotherapy to
seek out alternate coping skills are the mainstay of long term
treatment, but patients frequently need the immediate relief
obtained with benzodiazepines.
Benzodiazepines are best utilized for the alleviation of
anxiety related to acute stressors or during the latent period
of antidepressant effect. They are also used for insomnia.
Benzodiazepines are not recommended for the long-term
treatment of anxiety because of their cognitive and motor effects.
Short-acting benzodiazepines such as Xanax 0.25 0.5mg
145

PO TID PRN may be considered, with patient education about
the rationale behind the short-term prescription of potentially
abusable medications.
Buspirone can also be used for the long-term management of
anxiety.
146
PAIN MANAGEMENT
ELIZABETH PAULK, MD
147
PAIN MANAGEMENT
Pain is common in HIV and AIDS, and rate of undertreatment as high
as 80%. Especially for patients with a history of substance misuse.
Pain can be related to infection (neuropathy, myelopathy, secondary
infections), treatment (neuropathy from antiretroviral treatments), or
unrelated conditions.
PAIN MANAGEMENT IN AIDS
Pain management in HIV patients is similar to that employed

in other pain syndromes, especially cancer pain. The basic
principles are:
Assess pain regularly and believe the patients report

Match the pain medication to the patients pain level
Start low and titrate as needed
For chronic pain, use long acting formulations on a
schedule
Use short-acting formulations selectively for breakthrough
Anticipate side effects and prevent when possible
Non-opioid analgesics
Non-opioid analgesics should be the initial drug of choice for mild
pain, and may be used in combination products with opioids for
moderate to moderately severe pain.
Aspirin, acetaminophen (APAP), and non-steroidal anti-inammatory
drugs (NSAIDs) are all antipyretic and have analgesic dose ceilings.
Generally safe and can be as effective, as weak or low-dose opioids.
Unless contraindicated, at least one of these should be included in
every pain regimen. Additive effect with opioids.
Principal components of the World Health Organization (WHO) Pain
Ladder, which has been endorsed for use in management of pain
related to HIV/AIDS as well as cancer.
Step 1 consists of scheduled treatment with ASA, APAP, or an
NSAID, If pain persists or increases, then treatment moves to Step 2.
148
PAIN MANAGEMENT
Non-Opioid Analgesics
Drug
Dose
Comments
Aspirin
500-1000mg
(4000 mg
max daily)
Maximum effect at single dose of 6501300mg

Side effects: dyspepsia, bleeding,
hypersensitivity
Platelet inhibition
Salsalate
500-750
(4000 mg
max daily)
Same as above, but less platelet inhibition
Acetaminophen
(APAP)
650-1000
(4000mg
max daily)
Maximum effect at single dose of 6301300 mg

Limited by hepatic toxicity.
Give no more than 4g/d in normal
patients.
Even normally therapeutic doses can
be toxic in patients with liver disease,
alcohol use, or who are fasting.
NSAIDS
- Ibuprofen
- Naproxen
- Ketoprofen
- Indomethacin
- Sulindac
- Ketorolac
- Etodolac
COX-2 Selective
Inhibitors
- Celecoxib
- Valdecoxib
Corticosteroids
- Dexamethasone
- Methylprednisolone
- Prednisone
- Cortisone
- hydrocortisone
(mg/dose
initial dosing)
200-400
250-500
25-50
25
150-200
10 (30-60
IM)
200-400
100-200
10
0.75
4
5
25
Major side effects are the same for all

bleeding (from platelet inhibition and GI
irritation) and renal impairment.
Patient may respond better to one than
another.
Very useful for pain related to bony
lesions
Etodolac is largely COX-2 selective
Celecoxib contraindicated with sulfa
allergy
Does not eliminate risk of GI bleeding
Similar side effects as NSAIDS
Very expensive
Effective anti-inammatories
Especially useful for tumor inltration of
nerves or bones, nerve compression, or
increased intracranial pressure
Try for one week, and if effective titrate
to lowest effective dose. If not effective,
stop.
Agitation, dysphoria may occur
Gastric irritation, osteoporosis, adrenal
insufciency and other changes
associated with long-term use
149
PAIN MANAGEMENT
WHO Pain Ladder
OPIOID ANALGESICS
Principles of opioid analgesic use for chronic pain

1. If pain is mild, begin with step 1. If this fails, or if pain is moderate
to moderately severe, proceed to step 2.
2. Step 2 includes combinations of weak opioids with non-opioid
analgesics. Medication should be given on a scheduled basis, not
prn and acetaminophen content should not be greater than 4g/day.
A variety of formulations are available. If pain persists or increases
on Step 2, then proceed to step 3.
3. Step 3 includes pure opioids, one of which should be selected
based on the type and severity of pain, available routes of
administration, cost, adverse reactions, patient age, and hepatic
and renal function.
4. Begin with a low dose (based on the previous opioid requirement
if converting from a combination agent) of a sustained release
formulation (e.g., morphine sulfate SR) on a schedule (BID or
TID) with short acting formulations (e.g., morphine sulfate elixir
(Roxanol)) as rescue for breakthrough pain.
150
PAIN MANAGEMENT
5. The dose of rescue medication should be 5-15% of the total
daily dose, and should be available frequently (every 1 hour for
morphine sulfate elixir).
6. Sustained release preparations should be increased if patient is at
steady-state and requiring ve or more doses of rescue medication
per day.
151
152
153
*IR = immediate release; SR = sustained release

**Fentanyl patches come in a variety of strengths dosed as micrograms (mcg) per hour, and conversion to
morphine is variable. A 25 mcg/hr patch is roughly equivalent to 24-66mg of oral morphine a day. It is also
available as an oral transmucosal tablet for breakthrough pain.
*** Roxanol concentration is 20mg/ml
PAIN MANAGEMENT
Adjunctive Medical Therapies For Pain Syndromes
Caffeine: 65 to 200 mg enhances analgesic effect of
acetaminophen, aspirin or ibuprofen.
Hydroxyzine (Vistaril, and others): 50 to 100 mg IM may add to
the analgesic effect of opioids and is antiematic.
Anticonvulsants: pain relief is associated with neural membrane
stabilization (phenytoin), affecting Na channel activity
(carbamazepine), or interacting with the gamma aminobutyric
acid pathway (valproic acid, clonazepam). Anticonvulsants can
relieve neuropathic pain, trigeminal neuralgia, post-herpetic
neuralgia, neuralgias arising from nerve inltration with cancer,
and AIDS-associated peripheral neuropathy.
Tricyclic antidepressants: treat pain directly through modulation
of serotonin, an integral part of the descending endogenous pain
pathway, and through depression treatment, thus diminishing
pain perception. Can cause seizures, tachycardia, autonomic
dysfunction.
Tramadol (Ultram) useful in moderate to moderately severe
pain. Seizures can occur, and there is increased risk with history
of seizures or concurrent antidepressants, MAO inhibitors,
linezolid or antipsychotics. Dose 50mg PO q 4-6h. Seizures
associated with doses higher than 400mg per day.
Miscellaneous Agents
Mexiletine may be effective for trigeminal neuralgia or
neuropathic pain. Side effects include prolonged QT interval,
torsades de pointes, and sudden death.
Topical capsaicin reduces pain by interrupting nociceptive
transmission through depletion of substance-P in the
unmyelinated sensory bers. It may be useful in neuropathy and
radiculopathy. Main side effect is intense burning sensation at
application site.
COMMON SIDE EFFECTS OF OPIOIDS

Most of them can be managed so that patients can tolerate a dose
adequate for pain management.
Patients become tolerant to all side effects after a few days except
for constipation, which persists and is dose related.
Opioid-induced nausea: haloperidol very effective, or other antiemetics.
154
PAIN MANAGEMENT
Sedation usually abates as patient becomes tolerant. Stimulant
medications such as caffeine or methylphenidate may help.
Constipation should be prevented, usually using a combination
of softening agents (colace, lactulose) and stimulants (senna,
bisacodyl, MOM).
Pruritus mom caused chemically by histamine release. Usually timelimited and responds to antihistamines.
PAIN MANAGEMENT IN SUBSTANCE ABUSERS
It is ESSENTIAL to REMEMBER that pain is a complex phenomenon

and is best addressed in the context of a complete psychosocial
evaluation of the patient.
Patients with a history of substance abuse are common in the
population of patients with HIV/AIDS, and because of physician
fears about addiction and drug-seeking behavior they tend to be
undertreated.
The principles of treatment are just the same for patients without a
history of substance abuse: believe the patient report, individualize
treatment using the WHO pain ladder, use written contracts with
clear consequences for non-compliance, identify a single prescriber,
and use an approach that incorporates attention to psychosocial
issues and non-pharmacologic interventions.
155
156
WOMEN AND HIV/AIDS

LAURA ARMAS, MD
157
WOMEN AND HIV/AIDS

50% of the 40 million worldwide adults living with HIV/AIDS are
female.
In US female adult and adolescent AIDS cases increased 8% to
26% from 1986 to 2001. From 1998 through 2002 AIDS diagnoses
decreased 5% among men, but increased 7% in women.
In 2002, 35,000 reported HIV infections were contracted by sexual
intercourse: 68% men, 32% women. AIDS cases were 74% men,
26% women. Women are also diagnosed at an older age. Minorities
more than 80% of AIDS among women. (63% black)
An estimated 66% of AIDS in women and adolescent girls in 2001
were from heterosexual contact: 16% with an injection drug user,
50% with other high risk partners. 32% infected through injection
drug use.
These underestimate women and adolescent girls living with HIV
or AIDS, since many reside in states without integrated HIV/
AIDS surveillance. Number of reported HIV infected women and
adolescent girls exceeds the number with AIDS. HIV/AIDS was
5th leading cause of death for all U.S. women aged 25-44. Among
African American women in this same age group, HIV/AIDS was the
third leading cause of death in 1999.
Male to female transmission is more efcient probably due to the
larger volume and time of semen exposure than to cervico-vaginal
uids. Semen contains greater concentrations of HIV. Rate of
transmission per contact: female to male: 0.03-0.09%; male to
female: 0.05-0.15%; insertive anal intercourse: 0.08-3.2%.
Other STDs disrupt mucosal and skin barriers; ulcerative diseases,
(herpes, syphilis, chancroid) increase risk up to 7 fold.
Non-ulcerative infections, (gonorrhea, chlamydia or bacterial
vaginosis) linked to increased risk of HIV transmission. STDs in
the HIV+ partner associated with leukocytosis in seminal or cervical
secretions, and higher genital uid HIV concentrations.
Uncircumcised men 8 times more likely to transmit HIV. Cervical
ectopy also associated with increased risk for HIV transmission.
Sexual practices associated with increased transmission risk:
intercourse during menses, bleeding during intercourse, receptive or
insertive anal sex.
HIV concentraction in genital secretions during pregnancy is
increased, increasing risk of transmission.
Risk of transmission associated with higher serum viral load and
lower CD4. Presumably HAART can decrease risk.
Progesterone predominant conditions such as pregnancy upregulate
158
WOMEN AND HIV/AIDS

CCR5 and thin the vaginal mucosa, which that may increase risk of
infection.
Certain clades of HIV may have increased tropism towards
Langerhans cells lining cervical epithelium and male foreskin.
GENDER DIFFERENCES IN HIV MANIFESTATIONS
One study showed a 60% higher risk of disease progression in

women compared to men at the same viral loads and CD4+ count,
but another study did not.
Access to care and other social factors likely account for the
relatively higher mortality in women than in men.
Primary HIV infection in women is similar to men. Fever, arthralgia,
myalgia, diarrhea, vomiting and non-inguinal lymphadenopathy.
After seroconversion, 42% of infected women remain relatively
asymptomatic; some have recurrent candida vaginitis.
15% of women with HIV develope lymphadenopathy.
Bacterial pneumonia is initial presentation of HIV for up to 13% of
infected women, other less frequent symptoms are acute retroviral
syndrome (7%), systemic symptoms (night sweats, fever and weight
loss) (7%), immune thrombocytopenic purpura (5%), oral hairy
leukoplakia (3%) and multidermatomal zoster (1%).
Kaposis sarcoma remains the only AIDS-dening illness signicantly
more common in men than women (11% vs. 1.8%). Cervical cancer is
an AIDS dening illness in HIV-infected women.
HAART IN WOMEN
Too little is known about efcacy and toxicity of current antiretroviral
therapies, mainly because of low accrual rates for women in clinical
trials.
The Womens Integracy HIV Study: from 1996 1999, 50% of the
cohort reported HAART use which led to improved immunological
function, HIV suppression and decreased morbidity and mortality.
Women have lower rates of HAART adherence. When controlled for
social factors such as access to care, substance abuse, and living
conditions, no gender difference is detected.
No gender difference in efcacy of antiretroviral therapies. A recent
study with nelnavir showed similar viral suppression for men and
women, but women experienced a greater increase in CD4+ counts
than men (116 vs 84).
159
WOMEN AND HIV/AIDS

In HIV-infected women, deferral of HAART until the CD4+ count is
200-350 is a valid management strategy.
Women may have more nausea, vomiting, malaise and
dysesthesias, particularly with ritonavir, than men, but diarrhea
caused by PIs is more common in men.
Efavirenz may be teratogenic and should be avoided in women who
may become pregnant.
Lipodystrophy rates in PI-containing regimens as high as 18% in
women. Higher rate of increase in abdominal girth and breast size,
but less fat loss in limbs and buttocks, buffalo hump, elevations
of cholesterol or triglycerides. Glucose intolerance reported more
frequently in women.
Women, particularly pregnant women, more suceptible to
mitochondrial toxicity and lactic acidosis with ddI or D4T regimens.
Recent report of increased risk of nevirapine-induced hepatotoxicity
in women with CD4+ higher than 200, particularly if pregnant, and
advised against its use.
Drug interactions another concern, especially with oral
contraceptives. Several antiretrovirals interfere with metabolism
of ethinyl estradiol, there by decreasing its efcacy. No data yet on
use of contraceptive patch or vaginal implant. Most recommended
reversible contraceptive is depo-provera injection (150 mg IM
q3 months), but is frequently refused due to high incidence of
amenorrhea and weight gain.
Discuss reproductive issues thoroughly, since patients frequently
do not disclose their desire for pregnancy or contraception. Do not
miss opportunities to avoid risks in the ARV regimen and to educate
on the need for early referral to an obstetrician experienced in the
management of HIV-infected pregnant women.
160
CYTOMEGALOVIRUS (CMV) DISEASE IN HIV

NAIEL N. NASSAR, MD
161
CMV DISEASE IN HIV

CMV GI INFECTIONS
Most common viral infection of the GI tract in AIDS.

May involve esophagus, colon, or other parts of GI tract.
Characteristic endoscopic nding of CMV esophagitis is giant
supercial ulceration associated with lucent halo of edema in
distal esophagus. Colon involved in 5-10% of AIDS patients
and occurs with CD4 counts <100. Widely disseminated CMV
disease occurs in 45%-65% of patients with CMV colitis. Most
patients will have diarrhea (intermittent in ~30%), fever ( >80%),
and abdominal pain (45%-80%).
CMV RETINITIS
Most common ocular infection and leading cause of blindness in

AIDS.
Occurs when CD4 count <100 (esp. <50). Retinitis most
common manifestation, accounting for two-thirds of cases. In
pre-HAART era, CMV disease occurred in 10-45% of patients.
Incidence declined signicantly due to HAART.
CMV NEUROLOGIC SYNDROMES
CMV encephalitis may present as diffuse micronodular encephalitis or

ventriculo-encephalitis. Inammatory demyelinating polyneuropathy
(IDP) is most commonly associated with autoimmune disorders;
CMV may be culprit later in course of AIDS. CMV infection often the
etiology of progressive polyradiculopathy/myelitis and is an etiology of
mononeuritis multiplex, (see Neurological Complications).
OTHER
CMV Pneumonitis is uncommon cause of pneumonia in HIV and has

a poor prognosis. Only patients with biopsy-proven CMV disease and
no other pathogen to explain pneumonia should be treated for CMV
pneumonia. CMV lesions are uncdommon and are associated with a
poor prognosis.
RECOMMENDATIONS
Patients with GI or other serious CMV disease should receive

aggressive HAART, as CMV disease declined signicantly after the
widespread use of HAART.
Discontinuation of maintenance therapy when CD4 > 200 and
sustained complete viral supression for 6 12 months on HAART
162
163
164
165
166
DISSEMINATED MYCOBACTERIUM AVIUM COMPLEX (DMAC)

NAIEL N. NASSAR, MD
167

CLINICAL MANIFESTATIONS
A late manifestation of AIDS; median CD4 count at diagnosis is 13.

Fever, weight loss, diarrhea, night sweats, chills, abdominal
pain, chronic malabsorption, hepatosplenomegaly, diffuse
lymphadenopathy, and occasionally adrenal insufciency.
DIAGNOSIS
Clinical syndrome
Mycobacterial cultures of blood stool, liver, lymph nodes or bone
marrow biopsy.
Biopsy specimens reveal poorly formed granulomas and sheets of
acid-fast bacilli
Anemia, abnormal LFTs with increased alkaline phosphatase are
common.
TREATMENT
Colonization of the lungs or the GI tract with MAC in absence of

bacteremia should not be treated. Routine screening of sputum
or stool for MAC colonization or monthly blood cultures are not
recommended.
Azithromycin 500 mg PO QD plus ethambutol 15 mg/kg
Alternatives to Azithromycin include:
1) Clarithromycin
2) Rifabutin
3) Ciprooxacin
Rifabutin should not be administered with certain PIs or NNRTI. No
recommendation to adjust dose of either clarithromycin or PIs.
Treat empirically if patient has typical symptoms of disseminated
MAC; do not be delay pending culture results. Treatment improves
symptoms, quality of life, and survival.
Maintenance of secondary suppression: azithromycin plus
ethambutol preferred.
PRIMARY PROPHYLAXIS
Recommended when CD4 count <50

Azithromycin 1200 mg/week PO, or
Clarithromycin 500 mg PO BID, or
Rifabutin 300 mg PO QD.
168

Prophylaxis for MAC should be administered to pregnant women, but
may withhold during rst trimester.
DISCONTINUATION OF PRIMARY PROPHYLAXIS
Discontinue prophylaxis in patients with a CD4 100 and sustained VL

suppression for 36 months
RESTARTING PRIMARY PROPHYLAXIS
Restart prophylaxis, if CD4 falls to 50
DISCONTINUATION OF SECONDARY SUPPRESSION
CD4 increase to 100 following 612 months of HAART
169
170
FUNGAL INFECTIONS
SANJAY REVANKAR, MD
171
FUNGAL INFECTIONS
CANDIDIASIS (Candida spp.)
Most common fungal infection in HIV.

Almost exclusively causes mucosal infections (i.e. oropharyngeal
candidiasis (thrush) and esophagitis).
Candidemia and disseminated candidiasis rarely seen in HIV
patients unless secondary to intravenous lines or IVDU.
Resistance to uconazole associated with advanced AIDS (CD4 <50)
and prior exposure to uconazole. This is uncommon now due to
better therapy of HIV.
CRYPTOCOCCOSIS (Cryptococcus neoformans)

Encapsulated yeast with worldwide distribution. Infection occurs
through inhalation.
Most common cause of life-threatening fungal infection in HIV
patients.
Almost exclusively causes meningitis, though pneumonia and other
organ involvement can also be seen.
Prior to HAART, up to 8% of patients with AIDS developed
cryptococcal meningitis.
Histoplasmosis (Histoplasma capsulatum)
Dimorphic (yeast in tissue, mould in the lab) fungus endemic to the
Midwestern and Southern U.S. Infection is acquired via inhalation
and is mainly a primary infection or reinfection rather than a
reactivation disease.
Rates of disease as high as 25% in highly endemic areas.
No person-to-person spread.
Coccidioidomycosis (Coccidioides immitis)
Dimorphic fungus endemic to Southwestern U.S., northern Mexico,
and Central America.
Infection via inhalation of the highly infectious airborn arthroconidia.
Primary infection is common, though reactivation outside of endemic
areas can occur.
No evidence of person-to-person transmission.
Patients with HIV are at greater risk of dissemination and more
severe disease.
172
173
174
175
176
VIRAL HEPATITIS
RUTH BERGGREN, MD
177
VIRAL HEPATITIS
HEPATITIS C AND HIV CO-INFECTION
SCREENING
All HIV infected persons should be screened for viral hepatitis

(USPHS Guidelines).
2nd or 3rd generation enzyme immunoassay (EIA).
Severely immunocompromised persons may have false-negative
EIA. Qualitative PCR for HCV RNA used when there is a high
suspicion of HCV despite negative EIA test.
Patients with newly positive EIA have 15% chance HCV viremia has
already cleared.
All HIV patients should also be screened for immunity to Hepatitis A
and B, and those non-immune should be immunized
Inform HCV patients that alcohol consumption accelerates liver
damage, and that safest course is total abstention from alcohol.
BASELINE EVALUATION (After HCV infection has been conrmed)
Screen for alcohol and substance abuse, depression and suicidality

Quantitative HCV RNA PCR, HCV genotype
Complete metabolic panel, ferritin, uric acid
TSH
CBC with differential and platelet count
Hepatitis A IgG, Hepatitis B core IgG, Hepatitis B surface antigen
Alfa-fetoprotein (if cirrhotic)
ANA, RPR
Pregnancy test
A pre-therapy dilated eye exam is advisable, as interferon associated
with retinal vascular occlusions, optic neuropathy.
EKG and exercise tolerance testing indicated for individuals at risk
HCV genotyping should be performed before the liver biopsy, as
some patients infected with genotype 2 or 3 may be candidates for
therapy without liver biopsy.
LIVER BIOPSY
Obtained in most cases considered for treatment.

Performed by hepatologists or interventional radiologists.
Pathologist should provide numeric grade of inammation (0 to
4, indicating absent, mild, moderate, or severe inammation) and
numeric stage of brosis, also scored 0 to 4. Quantitative report
permits objective assessment of histological response to treatment.
178
VIRAL HEPATITIS
Biopsy complications requiring hospitalization in 1-3%
Mortality from liver biopsy approximately 1: 10,000.
Liver biopsy results help determine management. Mild brosis (stage
1) and remote infection may defer treatment, repeat liver biopsy in
1 to 2 years. Liver biopsy may identify additional diagnoses, e.g.
steatohepatitis, hemochromatosis, opportunistic infection.
POSSIBLE BENEFITS OF THERAPY
Possible to eradicate HCV. Sustained virologic response (SVR)

dened as negative HCV PCR at 48 weeks of therapy and again 6
months later
Reduce risk of liver failure
Reversal of cirrhosis
Reduce extrahepatic manifestations of HCV, (e.g. cryoglobulinemia)
and prevent hepatocellular carcinoma
Benets not limited to patients with SVR: virologic nonresponders
may improve histologically
Goals for virologic nonresponders are to prevent hepatic
decompensation and liver cancer with maintenance therapy.
HAZARDS OF THERAPY
Cr clearance < 50 contraindicates ribavirin, but not pegylated

interferon.
Contraindications to therapy with pegylated interferon and ribavirin:
serious depression, ongoing injection drug or alcohol abuse,
pregnancy, opportunistic infections, autoimmune diseases, coronary
artery disease, pancreatitis, and decompensated liver disease.
Ribavirin must not be coadministered with ddI due to risks of
mitochondrial toxicity and pancreatitis.
Ribavirin is teratogenic, and people on therapy must use two
methods of contraception, including a barrier method, through 6
months after completion.
TREATMENT OF CO-INFECTION:
No therapies yet FDA approved for the treatment of HCV in HIV

patients, but pegylated interferon alfa 2a, and pegylated interferon alfa
2b, with or without ribavirin, are approved to treat HCV monoinfection.
Studies in HCV monoinfected persons show that weight-based dosing
179
VIRAL HEPATITIS
of ribavirin (>10.6 mg/kg) and good adherence (better than 80% for
duration and 80% of peginterferon/ribavirin) doses can boost SVR to
60% in genotype 1 and 80-90% in genotypes 2 or 3.
Over 9 published studies have examined treatment of co-infected
HCV / HIV
ACTG 5071 showed 44% virologic response at week 24 in coinfected patients treated with peginterferon/ribavirin. SVR rate not
yet published, but SVR rates in the HAART era range 10-58%.
Current practice for HIV/HCV coinfected patients dictated by
standard of care applied to individuals with HCV monoinfection.
TREATMENT REGIMENS
Pegylated interferon alfa 2a (Pegasys) 180 mcg SQ once per week

for 48 weeks
OR
Pegylated interferon alfa 2b (Pegintron) 1.5 mcg/kg SQ once per
week for 48 weeks
AND
Ribavirin, 10.6 mg/kg po daily in divided doses (bid)
Erythropoietin and Neupogen (lgrastim) have been used to manage
anemia and neutropenia complicating this therapy.
MONITORING
Monitor for adverse events and drug interactions throughout

treatment. Screening for drug interactions includes review of
systems and lab values looking for evidence of mitochondrial toxicity,
lactic acidosis, pancreatitis, and diabetes.
Anemia managed with Epoietin Alfa (40,000 U SQ QW); and/or
reduce dose or discontinue ribavirin.
Neutropenia managed with Neupogen (300 mcg SQ TIW, titrate
to maintain ANC>/=750); reduce PEG IFN dose, or discontinue
treatment
Early virologic nonresponders (failure to have 2 log drop in HCV RNA
at 12 weeks) have virtually no chance of SVR, but may benet from
maintenance therapy.Virologic nonresponders at 24 weeks usually
have therapy discontinued, and may need repeat liver biopsy to guide
further management (maintenance half dose interferon)
180
SEXUALLY TRANSMITTED DISEASES

JAMES P. LUBY, MD
181

ULCERATIVE GENITAL LESIONS
HERPES SIMPLEX VIRUS
HSV-1 is usually found in oral lesions but also causes up to 30% of

rst episode genital herpes. HSV-2 occurs predominantly in genital
infections as grouped vesicles which rupture to form multiple shallow
painful ulcers. These may coalesce into one or more larger ulcers.
HSV is relatively common among HIV patients and may be severe,
painful, and atypical.
Inguinal lymphadenopathy, sacral radiculitis, with constipation,
urinary retention, and perigenital anesthesia may also occur.
Diagnosis by tissue culture isolation, Tzanck smear, or HSV-IFA is
useful.
Treatment
Acyclovir 400 mg PO TID for 710 days (5-10 days for recurrent
episodes)
Famciclovir 250 mg PO TID for 710 days (500 mg PO BID for
5-10 days for recurrences)
Valacyclovir 1 g PO BID for 710 days (5-10 days for recurrent
episodes)
If lesions persist consider acyclovir resistance. Treat with foscarnet
40 mg/kg IV Q8H until clinical resolution or topical cidofovir gel 1%
applied daily for 5 days
SYPHILIS
Primary Syphilis (Chancre)
Painless, (occasionally painful) solitary lesion with raised, welldened indurated borders and a clean base associated with nontender regional lymphadenopathy.
Secondary Syphilis
Flu-like symptoms, including myalgia, arthralgia, malaise, low-grade
fever, and lymphadenopathy, 4-10 weeks after the chancre appears.
Rash (75-100%), non-pruritic, maculopapular, affecting the trunk
and the limbs including soles and palms. It may be pustular, nodular,
eczematous, or plaque-like.
Condylomata lata broad-based, (at or heaped-up, eshy pearly gray
lesions in the anogenital area). Mucous patches occur in the mouth
182

or other mucous membranes. Large numbers of spirochetes may be
detected on darkeld microscopy on samples taken from the surface.
HIV patients are more likely to present in the secondary stage with
persistent chancres. Unusual rashes, papular or nodular eruptions,
nodular or ulcerative lesions with necrotic centers (lues maligna), and
keratoderma.
Latent Syphilis
Reactive syphilis serologic tests in the absence of clinical ndings.
Early latent syphilis is < 1 yr duration; late latent syphilis is > 1 yr
duration to guide therapy.
Patients with early latent syphilis are potentially infectious: less likely
with late latent syphilis.
HIV patients with late latent syphilis or syphilis of unknown duration
should have LP before treatment.
Tertiary Syphilis
Neurologic complications occur more frequently and earlier in HIV
patients. Common ocular ndings include uveitis, chorioretinitis and
retrobulbar neuritis.
Presents often with decreased vision, eye pain, optic neuritis/papillitis
and palsies of ocular motor nerves III and VI.
Otologic syphilis presents with progressive hearing loss and tinnitus.
The majority of symptomatic neurosyphilis cases among HIV patients
have a reactive CSF VDRL
Diagnosis of Syphilis
Fluorescent antibody staining may be useful
RPR plus MHA-TP or other treponomal comrmatory test
CSF analysis and VDRL
Dark eld or immunouorescent microscopy of lesions
Treatment
Penicillin, is the antimicrobial of choice in the treatment of syphilis in
HIV patients. (see Appendix I)
CHANCROID
An estimated 10% of patients who have chancroid are co-infected

with syphilis or HSV.
Multiple, ragged, and painful ulcers which are not indurated
183

(soft chancre), with a necrotic exudate and easily bleeds with
manipulation. The combination of a painful ulcer and tender,
suppurative inguinal adenopathy is almost pathognomonic.
Diagnosis
A probable diagnosis may be made if:
One or more painful genital ulcers
No evidence of syphilis or HSV infection of ulcer
Treatment
Azithromycin 1 g PO in a single dose.
Ceftriaxone 250 mg IM in a single dose.
Ciprooxacin 500 mg PO BID for 3 days.
Erythromycin 500 mg PO QID for 7 days.
HIV-infected patients may require longer courses of therapy
LYMPHOGRANULOMA VENEREUM
A rare disease caused by invasive C. trachomatis serovars L1, L2,

and L3
Transient painless ulcer followed by chronic regional suppurative
lymphadenitis
Genital inguinal or perineal lymphedema
Diagnosis: serology, (chlamydia trachomatis serovar L)
Treatment: doxycycline, TMP-SMX, azithromycin, uoroquinolone
GRANULOMA INGUINALE (DONOVANOSIS)
Sub acute to chronic granulomatous inguinal or genital ulcer

Diagnosis: biopsy
Treatment: TMP-SMX. May add gentamicin. Relapse common.
NON-ULCERATIVE GENITAL LESIONS

GONORRHEA
Because gonococcal infections among women often are

asymptomatic, screen women at high risk for STD.
Diagnosis
Gram stain of urethral or cervical smears, (gram-negative
intracellular diplococci) and culture.
184

Gene probes
Treatment of uncomplicated gonococcal infections of the cervix,
urethra, and rectum
Ceftriaxone 125 mg IM in a single dose.
Ciprooxacin 500 mg orally in a single dose, levooxacin 250 mg
orally in a single dose.
PLUS
Azithromycin 1 g orally in a single dose, or
Doxycycline 100 mg orally twice a day for 7 days.
ALTERNATIVE REGIMENS
Spectinomycin 2 g IM in a single dose is useful for treatment of
patients who cannot tolerate cephalosporins or quinolones.
Other injectable cephalosporins include ceftizoxime 500 mg IM,
cefotaxime 500 mg IM, and cefoxitin 2 g IM with probenecid 1 g
orally. None of these injectable cephalosporins offers any advantage
in comparison with ceftriaxone, and clinical experience with these
regimens for treatment of uncomplicated gonorrhea is limited.
Azithromycin 2 g orally in a single dose is effective for uncomplicated
gonococcal infection, but it is expensive and causes gastrointestinal
distress too often to be recommended for treatment of gonorrhea.
At an oral dose of 1 g, azithromycin is insufciently effective, curing
only 93% of patients. Either regimen effectively treats chlamydia
coinfection.
Treatment of uncomplicated gonococcal infection of the pharynx
Gonococcal infections of the pharynx are more difcult to eradicate
than infections at urogenital and anorectal sites.
Although chlamydial co-infection of the pharynx is unusual,
coinfection at genital sites and mixed syndromes sometime
occur. Therefore, treatment for both gonorrhea and chlamydia is
suggested.
Ceftriaxone 125 mg IM in a single dose, or
Ciprooxacin 500 mg orally in a single dose.
PLUS
Azithromycin 1 g orally in a single dose, or
Doxycycline 100 mg orally twice a day for 7 days.
Treatment of gonococcal conjunctivitis
Ceftriaxone 1 g IM in a single dose, and lavage the infected eye with
185

saline solution once as needed.
Treatment of disseminated gonococcal infection
Ceftriaxone 1 g IM or IV every 24 hours. Alternative initial regimens
include cefotaxime 1 g IV Q8H or ceftizoxime 1 g IV Q8H. For
persons allergic to -lactam drugs; ciprooxacin 400 mg IV Q12H, or
spectinomycin 2 g IM Q12H.
All regimens should be continued for 2448 hours after improvement
begins, at which time therapy may be switched to ciprooxacin
(ooxacin), 500 mg PO BID to complete a full week of therapy.
Treatment of gonococcal meningitis and endocarditis
Ceftriaxone 12 g IV Q12H. Duration of therapy is 1014 days
for meningitis and at least 4 weeks for endocarditis. Seek ID
consultation.
NONGONOCOCCAL URETHRITIS
C. trachomatis most common, U. urealyticum HSV, T. vaginalis, and

C. albicans are infrequent causes of NGU (<5%).
Dysuria and sparse mucoid urethral discharge occur in about 38% of
patients.
Treatment: azithromycin 1 g orally in a single dose, or doxycycline
100mg PO BID for 7 days. Alternative regimens include erythromycin
500mg PO Q6H for 7 days, or levooxacin 500 mg once daily for 7
days.
DISEASE CHARACTERIZED BY VAGINAL DISCHARGE

BACTERIAL VAGINOSIS
Overgrowth of vaginal anaerobes with concomitant reduction in

Lactobacillus sp.
Diffusely adherent white or gray vaginal discharge with a high pH
(>5.0), and a positive whiff test upon addition of KOH, and clue
cells (epithelial cells coated with bacteria) on smear.
Treatment
Metronidazole 500 mg orally twice a day for 7 days, or
Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days, or
186

Metronidazole gel 0.75%, one full applicator (5 g) intravaginally
twice a day for 5 days.
Alternative regimens include metronidazole 2 g orally in a single
dose or clindamycin 300mg orally twice a day for 7 days.
TRICHOMONIASIS
Copious, homogeneous, greenish or dishwater-like discharge.

Associated with premature rupture of the membranes and
preterm delivery.
Diagnosis by wet mount showing motile, agellated T. vaginalis,
or visible on Pap smears.
Treatment
Metronidazole 2 g orally in a single dose or 500 mg BID for 7
days. Partners should be treated simultaneously.
187
188
THE HIV-INFECTED TRAVELER

PAUL SOUTHERN, MD
189

PRE-TRAVEL PREPARATIONS
A knowledge of which countries prohibit or restrict travel by HIVinfected individuals is a necessary part of pre-travel preparations.
Many countries either do not allow HIV-infected persons to enter or
require some form of registration upon entry. Some require HIVantibody status to be tested within their country. .
There is a relatively good correlation between CD4 counts and the
risks of certain infections, as well as the risks for certain vaccines.
The HIV-infected traveler should know his/her CD4 status prior to
making travel plans and be aware of the risks involved. Some live
vaccines are absolutely contraindicated, while others are relatively
contraindicated. (see below)
Personal Protective Equipment
Personal protective measures to reduce arthropod borne infections
include insect repellents (DEET), insecticides (permethrin) and
wearing clothing that covers arms and legs.
Sunscreens and broad-brimmed hats will protect against sun
exposure.
Frequent Travel - Related Infections
The most frequent travel-related infections are enteric pathogens.
Various types of enteric-pathogenic Escherichia coli are the most
common.
Others: Salmonella, Shigella, Campylobacter, Cyclospora,
Cryptosporidium, Isospora species, Giardia intestinalis and
Entamoeba histolytica.
Except for the E. coli types, the HIV-infected traveler is at greater
risk than the general population for severe infection and/or serious
complications, including extra-intestinal manifestations. Appropriate
food and water (including ice) precautions must be taken .
Prescribe loperamide (Imodium), and a uoroquinolone (e.g.,
ciprooxacin or levooxacin) for self-administration in the event of
mild to moderate gastrointestinal symptoms.
More serious forms of enteritis or colitis should prompt medical
attention from a qualied provider. Immunize against hepatitis A
and B and consider immunization against typhoid fever (injectable
vaccine, not the oral live vaccine).
190

Respiratory infections are more common in some developing
countries. This includes inuenza, tuberculosis and bacterial
pneumonia. The HIV-infected traveler should have regular inuenza
immunizations and should remember that the inuenza season in
the southern hemisphere is during the Autumn-Spring months (AprilOctober).
In most tropical climates inuenza can be transmitted year-around.
BCG vaccine cannot be recommended for prevention of tuberculosis,
but know that in some areas (particularly sub-Saharan Africa) the
prevalence of tuberculosis, including multi-drug resistant strains is
increased. Anti-tuberculosis chemoprophylaxis is not usually advised
for travelers.
Some infections are more severe in immunocompromised hosts:
visceral and mucocutaneous leishmaniasis, toxoplasmosis, American
trypanosomiasis (Chagas disease), yellow fever and babesiosis.
VACCINES FOR HIV-INFECTED TRAVELERS

Not Contraindicated
1. Hepatitis A/Hepatitis B (a combination vaccine is available,
Twinrix)
2. Inactivated polio (IPV)
3. Inactivated Typhoid (Typhim Vi, injectable)
4. Haemophilus inuenzae type B (HiB)
5. Streptococcus pneumoniae, 23-valent (Pneumovax)
6. Inuenza virus (irrespective of season)
7. MMR (consider booster if many years since primary series)1
8. Diphtheria/Tetanus (dT)
9. Meningococcal polysaccharide vaccine (particularly if the itinerary
involves the meningitis belt of Africa, or a pilgrimage to Mecca for
the hajj).
10. Japanese encephalitis (only if the itinerary includes protracted
stays in rural locations in Asia).
11. Rabies (particularly if exposures are at all likely).
Contraindicated
1. Oral polio (OPV; it is no longer available in the USA, and should not
be administered elsewhere).
2. Oral typhoid
3. Yellow fever 2
191

4. BCG
5. Varicella
1
A possible risk of increased (probably transient) HIV viral load

following MMR vaccination, but unknown clinical signicance.
Some countries may require proof of vaccination as a
condition of entry. May need a physicians letter of medical
contraindication. If an HIV-infected person insists upon
traveling to a yellow fever endemic location, then extremely
strict insect avoidance measures must be practiced. Only as
a last resort, and with clear warnings, should the vaccine be
administered.
RECOMMENDED PROPHYLAXIS REGIMENS

Malaria
The same as in travelers without HIV infection (Refer to the CDC
Yellow Book, Health Information for International Travel, or to the
WHO book, International Travel and Health).
For areas with chloroquine-susceptible Plasmodium falciparum and
Plasmodium vivax (Refer to CDC/National Center for Infectious
Diseases web site on Travelers Health for updated information for
travel destinations)
1. Chloroquine phosphate (Aralen) 500 mg salt (300 mg base) once
weekly beginning 1-2 weeks before travel, and continuing for 4
weeks after leaving malarious region, or
2. Hydroxychloroquine sulfate (Plaquenil) 400 mg weekly, same
regimen as chloroquine.
For areas with chloroquine-resistant Plasmodium falciparum and/or
Plasmodium vivax (conrm as above for current information)
1. Meoquine (Lariam) 250 mg once weekly beginning 1-2 weeks
before travel, and continuing for 4 weeks after leaving malarious
region1, or
2. Doxycycline 100 mg daily beginning on day of travel, and continuing
for one week after leaving malarious region 2, or
3. Atovaquone/Proguanil (Malarone) one adult tab (atovaquone 250
mg/proguanil 100 mg) daily beginning on day of travel and continuing
for one week after leaving malarious region3, or
192

4. Primaquine phosphate 26.3 mg salt (15 mg base) daily beginning
on day of travel, and continuing for one week after leaving malarious
region.4
For terminal prophylaxis/treatment after treating P. vivax or P. ovale
infection (and some experts recommend after exposure):
1. Primaquine phosphate 26.3 mg salt (15 mg base) daily for 14
days.5
For emergency/presumptive therapy when no medical facility readily
available
1. Pyrimethamine/sulfadoxine (Fansidar) 3 tablets PO as single dose. 6
1
3
4,5
Contraindicated in persons with a history of seizures, psychiatric

disorders, or depression.
Contraindicated during pregnancy. Should not be taken
before lying down (erosive esophagitis). May predispose to
phototoxicity (protect from sun exposure).
Most expensive option; probably prohibitive for prolonged usage.
Contraindicated in persons with G6PD deciency;
contraindicated during pregnancy. In areas where P. vivax
is relatively resistant, a dose of 30 mg base daily may be
necessary.
No longer available in the USA, but is available elsewhere.
Has caused Stevens-Johnson syndrome.
193
Appendix I
195
196
Appendix I (continued)
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
Appendix II
213
214
Appendix II (continued)
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
Appendix III
INDEX
A
Abacavir (ABC) 40, 41, 48, 49,
213
Acyclovir 182, 213
Adrenal 111
Amphotericin B 112, 214
Amprenavir (APV) 50, 70
Anemia 28, 136, 180
Anorexia 116
Anxiety 145
Aphthous 80, 81, 195
Atazanavir 41, 43, 50, 214
Atovaquone 67, 68, 192
Azithromycin 168, 184, 185, 215
AZT (Zidovudine) 40, 41, 43, 48,
49, 53, 81, 96, 97, 117,
123, 243
B
Bacillary angiomatosis 124, 195
Bacterial vaginosis 16, 195
BCG 29, 69, 191, 192
Blastocystis 83, 85
Breastfeeding 17
C
Campylobacter 83, 85, 190, 207
Candida 81, 82, 87, 88, 92, 172
Candidiasis 13, 26, 28, 81, 172
Cefotaxime 185, 186
Cefoxitin 185
Ceftriaxone 184, 185, 186, 216
Chancroid 158, 183, 196
Chlamydia 158, 184, 185
Cidofovir 101, 117, 182, 217
Ciprooxacin 184, 218
Clarithromycin 168, 218
Clostridium diffcile 197
Clindamycin 67, 73, 186, 219

Cytomegalovirus (CMV) 13, 26,
29, 74, 80, 81, 82, 83, 85,
86, 87, 88, 90, 95, 96, 97,
100, 101, 111, 112, 117,
162, 163
Coccidioidomycosis 13, 73, 172
Colitis 100, 162, 190
Combivir 219
Cryptococcus 73, 88, 92, 94, 97,
172
Cryptococcosis 13, 94, 95, 172
Cryptosporidium 83, 84, 85, 87,
88, 190
Cyclospora 83, 84, 190
Cytomegalovirus 9, 13, 81, 85,
86, 92, 162, 163
D
d4T (Stavudine) 41, 43, 48, 49,
238
Dapsone 26, 220
ddC (Zalcitibine) 43, 48, 49, 81,
88, 97, 242
ddI (Didanosine) 41, 43, 48, 49,
80, 88, 97, 117, 144, 160,
179, 221
Dementia 90, 98, 100
Depression 140, 141, 142
Dexamethasone 94, 113, 149
Didanosine (see ddI)
Direct Fluorescent Antibody
(DFA) 66, 84
Dysphagia 81
245
INDEX
E
Efavirenz 36, 41, 43, 53, 160, 222
ELISA 18, 22, 27, 28, 84
Emtriva (see FTC)
Enfuviritide 222
Encephalitis 90
Entamoeba 83, 190
Entry Inhibitors 43
Eosinophilia 111
Epzicom 223
Erythropoietin 180
Esophagitis 13, 28, 86, 100, 162,
172, 193
F
Famciclovir 182, 223
Fenobrate 224
Filgrastim 180, 224
Flucocytosine 226
Fludrocortisone 111, 113
Fos-amprenavir 226
Foscarnet 112, 182, 227
FTC (Emtriva) 41, 48, 222
G
Gabapentin 98, 102, 227
Ganciclovir 95, 227
Gatioxacin 228
Gembrozil 228
Genotype 29, 47, 178, 180
Genotypic 46, 53
Giardia 83, 84, 85, 190
Glycemia 110
Gonorrhea 85, 86, 184, 185, 186
H
Hepatitis A (HAV) 28, 29, 30,
178, 191
246
Hepatitis B (HBV) 22, 28, 29, 30,

52, 124, 178, 191
Hepatitis C (HCV) 28, 29, 30, 43,
52, 117, 124, 178, 179,
180, 191
Herpes Simplex (HSV) 13, 80, 81,
82, 83, 85, 86, 88, 90, 92,
182, 201
HHV-8 74, 126
Histoplasma 73, 84, 92, 172
Histoplasmosis 13, 85, 172, 175,
201
HIV-2 16, 17, 18, 19
Hydrocortisone 111, 113
Hypoglycemia 110
I
Immunization (see vaccine)
Indinavir (IDV) 41, 49, 113, 229
Inuenza 29, 72, 191
Interferon 178, 179, 180
Isospora 83, 84, 85, 87, 190
Isosporiasis 13
Itraconazole 113, 230
K
Kaletra (LPVr) 38, 43, 232
Kaposis sarcoma 13, 28, 86, 87,
92, 159, 202
Ketoconazole 111
L
Lamivudine (3TC) 40, 41, 48,
53, 231
Leucovorin 232
Levooxacin 185, 231
Levothyroxine 113
Lipids 110
INDEX
Lipodystrophy 39, 110
Lopinavir (LPV) 50
Lymphogranuloma 184, 202
Lymphoma 13, 82, 85, 86, 88, 92,
93, 128, 133
M
Malaria 192
Mania 144, 145
Megestrol acetate 233
Meningitis 26, 27, 68, 70, 73, 90,
93, 94, 98, 172, 174, 186,
191
Microsporidia 83, 97, 202
Molluscum contagiosum 202
Mutations 17, 27, 43, 46, 47, 48,
49, 50
Mycobacterium avium complex
14, 84, 203
Mycobacterium kansasii 14, 203
Mycobacterium tuberculosis (see
Tuberculosis)
Myelopathy 90, 95, 96, 97, 148
Myopathy 96, 97, 113, 122, 123
N
Nelnavir (NFV) 41, 49, 53, 233
Neuropathy 26, 28, 95, 97, 123,
148, 154, 178
Neutropenia 28, 143, 180
Non-nucleoside reverse
transcriptase inhibitors
(NNRTI) 32, 36, 40, 43,
49, 70, 110, 141, 168
Nocardia 71, 92, 204
Non-opioid 148
Nucleoside reverse transcriptase
inhibitors (NRTI) 32, 43,
48, 88, 110
Nucleotide analogue 35, 36

Nystatin 81
O
Opioid 148, 150, 152, 153
Oral hairy leukoplakia 80, 204
Oraquick 22
Oseltamivir 72, 234
Oxandrolone 234
P
p24 17, 23, 27, 29
Pancreatitis 86, 87, 88, 145, 179,
180
Pap smear 29, 86
Pneumocystis carinii pneumonia
(PCP) 14, 27, 66, 67, 68,
69, 71, 73, 74, 111
PCR 17, 23, 27, 28, 69, 90, 93,
94, 100, 101, 178, 179
Penicillin 99
Pentamidine 67, 68, 88
Perinatal 17, 18, 101
Permethrin 190, 235
Phenotype 46, 47
Pneumococcal vaccine 29
Pneumocystis jerovici 14
Pneumonia 14, 66, 71
Polio vaccine 30
Polymyositis 96, 97, 122, 123
Prednisone 67, 97, 111
Pregnancy 28, 68, 69, 71, 158,
160, 179, 193
Primaquine 193
Proguanil 192
Protease inhibitor (PI) 36, 37, 38,
40, 43, 70, 110, 113, 141,
143, 160
247
INDEX
P (continued)
Psychosis 143, 144
Pyrimethamine 193, 235
R
Rabies 30, 191
Resistance 16, 17, 29, 39, 40, 42,
43, 46, 47, 48, 49, 50, 53,
70, 72, 91, 110, 182
Retinitis 13, 100, 164
Rhodococcus 71, 73, 92, 207
Rifabutin 70, 113, 236
Rifampin 69, 70, 113, 236
Ritonavir (RTV) 41, 49, 91, 102,
113, 237
Rotavirus 83
RPR 52, 86, 99, 178, 183
S
Salmonella 14, 83, 85, 190, 207
Saquinavir (SQV) 36, 113, 238
Scabies 28, 207
Seborrheic dermatitis 28, 207
Shigella 83, 85, 190, 207
Sinusitis 72
Spectinomycin 185
Stavudine (see d4T)
Steroids 100, 101
Streptococcus 76, 191
Syphilis 26, 27, 28, 90, 98, 99,
158, 182, 183, 184, 208
T
Tenofovir (TNF) 40, 41, 43, 49,
53, 239
Thalidomide 81, 82
Thrombocytopenia 28
Thrush (see Candidiasis)
Thyroid 29, 111
248
TMP/SMX 67, 68, 71, 73

Toxoplasmosis 14, 90, 209
Trichomoniasis 209
Trizivir 35, 241
Truvada 36, 241
Tuberculosis 14, 26, 27, 84, 86,
90, 92, 93, 111, 191, 203
U
Urethritis 28, 122
Uveitis 122
V
Vaccine 27, 29, 30, 69, 71, 72,
190, 191, 192
Valacyclovir 182, 242
Varicella 29, 30, 92, 192, 210
W
Warts 210, 211, 212
Y
Yersinia 84, 85, 212
Z
Zalcitabine (see ddC)
Zidovudine (see AZT)
TABLE OF CONTENTS
EPIDEMIOLOGY OF HIV INFECTIONS & AIDS .................................... 11
HIV TRANSMISSION, INCLUDING HIV-2............................................15
HIV TESTING ..............................................................................21
INITIAL WORK-UP OF HIV ..............................................................25
ANTIRETROVIRAL THERAPY ............................................................31
RESISTANCE TESTING ...................................................................45
MANAGEMENT OF PERSONS EXPOSED TO HIV ..................................51
CLINICAL MANIFESTATIONS OF HIV INFECTION
DERMATOLOGICAL COMPLICATIONS .............................................55
PULMONARY COMPLICATIONS ....................................................65
GASTROINTESTINAL COMPLICATIONS ...........................................79
NEUROLOGICAL COMPLICATIONS ................................................89
ENDOCRINOLOGIC & METABOLIC COMPLICATIONS .......................109
RENAL DISORDERS................................................................ 115
RHEUMATOLOGIC COMPLICATIONS ............................................121
MALIGNANCY & HEMATOLOGIC COMPLICATIONS ..........................125
MENTAL HEALTH DISORDERS ..................................................139
PAIN MANAGEMENT ...............................................................147
WOMEN AND HIV/AIDS ........................................................157
COMMON CO-INFECTIONS IN HIV
CYTOMEGALOVIRUS ...............................................................161
DISSEMINATED MYCOBACTERIUM AVIUM COMPLEX (DMAC) ........167
FUNGAL INFECTIONS ..............................................................171
VIRAL HEPATITIS ...................................................................177
SEXUALLY TRANSMITTED DISEASES ..........................................181
THE HIV-INFECTED TRAVELER.................................................189
APPENDIX I: THERAPY FOR FREQUENT INFECTIOUS DISEASES
IN HIV PATIENTS ...................................................195
APPENDIX II: HIV RELATED DRUGS, INDICATIONS, DOSAGES
AND MOST COMMON SIDE EFFECTS .........................213
APPENDIX III: DISCONTINUATION OF OPPORTUNISTIC INFECTION
PROPHYLAXIS/MAINTENANCE AFTER IMMUNE
RECONSTITUTION ...................................................244
INDEX.......................................................................................244

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PARKLAND

NAIEL N. NASSAR, M.D.

NAIEL N. NASSAR, M.D., F.A.C.P.

PHILIP KEISER, M.D.

Associate Professor of Medicine

CLARK R. GREGG, M.D.

To send your comments or to request additional or future copies

EPIDEMIOLOGY OF HIV INFECTION & AIDS

EPIDEMIOLOGY OF HIV INFECTION & AIDS

Number of people living

AIDS deaths in 2002

United States Summary of the AIDS Epidemic 1981-2001

Exposure Categories for AIDS Cases Reported in 2001: United States

Injection Drug Use (IDU)

MSM & IDU

EPIDEMIOLOGY OF HIV INFECTION & AIDS

Consists of one or more of the following:

Consists of one or more of the following:

Includes the conditions listed in the AIDS

Conditions included in the 1993 AIDS surveillance

Candidiasis of bronchi, trachea, or lungs

EPIDEMIOLOGY OF HIV INFECTION & AIDS

HIV TRANSMISSION, INCLUDING HIV-2

HIV TRANSMISSION, INCLUDING HIV-2

HIV TRANSMISSION, INCLUDING HIV-2

HIV TRANSMISSION, INCLUDING HIV-2

HIV TRANSMISSION, INCLUDING HIV-2

Risk of Transmission per coital act

Acute Retroviral Syndrome

HIV Disease Progression

AIDS is reportable by name in all states. Most states have laws

INITIAL WORKUP OF HIV

INITIAL WORKUP OF HIV

Acute retroviral syndrome represents the initial viral burst of

WORKUP OF ESTABLISHED HIV INFECTION

INITIAL WORKUP OF HIV

INITIAL WORKUP OF HIV

INITIAL WORKUP OF HIV

INITIAL WORKUP OF HIV

GOALS OF HIV THERAPY

Recommended Treatment Initiation Paramenters

CD4 Cell Count

Adapted from DHHS Treatment Guidelines

HIV therapy is lifelong commitment to taking medications

INITIAL ANTIRETROVIRAL THERAPY

Highly active antiretroviral therapy (HAART) consists of an active

ABC/3TC combo pill

*Atazanavir is a preferred agent in the International AIDS Society - USA treatment

Adherent patients who fail to achieve an undetectable HIV-1 RNA

CLASS/AGENT SPECIFIC ISSUES

Assess net effect

USEFUL WEBSITES FOR INTERPRETING GENOTYPES AND FOR

RECOMMENDATIONS: APPLICATION OF HIV DRUG RESISTANCE

MANAGEMENT OF PERSONS EXPOSED TO HIV

MANAGEMENT OF PERSONS EXPOSED TO HIV

HIV has been transmitted to health care workers primarily by

Nosocomial exposure to HIV infection is best managed in

MANAGEMENT OF PERSONS EXPOSED TO HIV

THERAPY FOR EXPOSURE

Therapy for should be initiated as soon as possible after the

Worldwide, reported prevalence of TB in AIDS ranges from

Bacterial pneumonia most common form of pneumonia in HIV;

Inuenza common in adults (~5%-40% of the general population),