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Theme of the practical class:

HIV-INFECTION

The Activator: HIV - the RNA-containing virus concerning to family of


Retroviruses, subfamily of Lentiviruses, causing slow infection of animals.
HIV is unstable in an environment. The HIV is adsorbed on cells which structure
of a membrane includes protein CD4 being a receptor for protein of a virus gp120. It is
Т-lymphocytes - helpers, macrophages, B - lymphocytes, cells of neuroglia, a mucous
membrane of intestine, dendritic and some other cells. Most frequently Т-lymphocytes-
helpers (cells CD4) are damaged.
Source of an infection: the ill person or an asymptomatic virus carrier. HIV is
revealed in all liquid environments of an organism. The greatest danger represent blood
(infecting doze of a virus contains in 0,1 ml) and the sperm, containing sufficient for
infection a doze of a virus, and also vaginal and cervical secrets, breast milk.
The Infection is transferred by three ways: sexual, parenteral and from mother to
a fetus.
Clinic
The incubatory period at the HIV-infection makes from 2-3 weeks about 3
months, in single instances - about one year. After it 50-90 % of the infected have
symptoms of acute HIV-infection. Most frequently grippe-mononucleosoformed
syndrome accompanying with a fever, tonsillitis, pharyngitis, lymphoadenopathy,
hepatosplenomegaly is met. At some patients short-term diarrhea, unstable skin rash are
observed, sometimes there is serous meningitis. Duration of acute HIV-infection
changes is from several days about 2-3 months, but usually makes 2-3 weeks. Acute
HIV-infection, as a rule, passes in asymptomatic. The following period - latent (virus
carriage) begins; it proceeds some years (from 1 till 8 years, sometimes more) when the
person counts itself healthy, conduct a usual way of life, being a source of an infection.
Much less often after a sharp infection the stage of persisting generalized
lymphoadenopathy (PGL) begins, and in unusual cases disease at once progresses down
to a stage of AIDS. PGL is characterized by increase of lymphatic nodes in two and
more groups (behind exception of inguinal lymph nodes at adults), keeping not less than
3 months. Lymph nodes of 1 sm and more at adults and reach in diameter of 0,5 sm - at
children. The most frequently cervical, occipital, axillary lymph nodes are increased.
They are elastic, not soldered with subject tissue; skin above them is not changed. Stage
of PGL also lasts rather long - till 5-8 years during which lymphatic nodes can decrease
and again be increased. In this period gradual decrease of level of CD4-lymphocytes, on
the average with speed of 50-70 cells in 1 mm3 per one year is marked. At stages of an
asymptomatic infection and PGL patients, as a rule, to doctors do not address and come
to light at casual inspection.
After these stages which general duration can vary from 2-3 till 10-15 years, the
stage of secondary diseases begins. There are various infections of viral, bacterial,
fungoid nature which for the present proceed rather favorably and are stopped by usual
therapeutic means. There are repeated diseases of the upper respiratory ways - otitis,
sinuitis, tracheobronchitis etc., superficial lesions of a skin - the located skin-mucous
form of recidivating simple herpes, recidivating surrounding herpes, candidosis of
mucous membranes, dermatomycosises etc.
Then these changes become deeper, they do not react to standard methods of
treatment, getting persistent, long character. The person starts to grow thin with loss of
weight of a body up to 10 %, a fever, night sweats and diarrhea are appeared.
On a background of increasing immunosuppression the heavy progressing
diseases proceeding with lesion of one or several organs and systems: a brain, lungs, a
liver, a gastrointestinal tract are developed. They also carry a difficult character,
representing threat for life. In process of decrease of a level of CD4 - cells pathological
process accepts irreversible current: AIDS – indicated diseases are shown in the various
combinations, even adequate therapy does not bring expected effect. The most
frequently pneumocystic pneumonia, toxoplasmosis, cryptococcal meningoencephalitis,
generalized cytomegaloviral infection (encephalitis, retinitis, esophagitis, hepatites),
sepsis of mixed etiology (viral-bacterial-fungoid), generalized Kapochi’s sarcoma,
cavernous tuberculosis of lungs, etc. are met.
Especially it is necessary to stop on specific lesion of nervous system which clinical
manifestations can be found out at various stages of the HIV-infection. In acute stage of
the HIV-infection the serous meningitis is possible; progressing of the disease is shown
by a syndrome of chronic weariness, neuropathias. But development of dementia (loss of
memory, destruction of the person) as consequence of progredient (with steady
deterioration) current of encephalitis is considered the most typical. Dementia can be a
unique clinical symptom, but more often it is combined with the various diseases caused
by immunodeficiency.

The Russian clinical classification of the HIV-infection


( V.I.Pokrovsky, 2001)
1. Stage of incubation.
2. Stage of initial manifestations
Variants of current:
A. Asymptomatic;
B. The acute HIV-infection without secondary diseases;
C. The acute infection with secondary diseases.
3. Latent stage.
4. Stage of secondary diseases
4A. Loss of weight less than 10 %; fungoid, virus, bacterial defeats of a skin and
mucous membranes; herpes zoster; repeated pharyngitises, sinusitises.
Phases: Progressing (on a background of absence of antiretroviral therapy, on a
background of antiretroviral therapy).
Remission (spontaneous, after antiretroviral therapy which was carried earlier, on a
background of antiretroviral therapy).
4B. Loss of weight more than 10 %; inexplicable diarrhea or a fever more than one
month; hairy leukoplakia, tuberculosis of lungs; repeated or proof viral, bacterial,
fungoid, protozoan lesions of internal organs; repeated or disseminated herpes zoster;
located Kaposhi’s sarcoma.
Phases: Progressing (on a background of absence of antiretroviral therapy, on a
background of antiretroviral therapy).
Remission (spontaneous, after antiretroviral therapy which was carried earlier, on a
background of antiretroviral therapy).
4C. Cachexy; generalized bacterial, viral, fungoid, protozoan and parasitic diseases;
pneumocystic pneumonia; candidosis of an esophagus, bronchial tubes, lungs;
extrapulmonary tuberculosis; atypical mycobacteriosises; disseminated Kaposhi’s
sarcoma; lesions of the central nervous system of various etiology.
Phases: Progressing (on a background of absence of antiretroviral therapy, on a
background of antiretroviral therapy).
Remission (spontaneous, after antiretroviral therapy which was carried earlier, on a
background of antiretroviral therapy).
5. Terminal stage.

Laboratory diagnostics
Specific diagnostics. In Russia standard inspection on the HIV-infection now
begins with statement IFA (immunofermenative analysis), then specificity of antibodies
confirm in immune blotting. Detection of a genetic material of a virus in the polymerase
chain reaction (PCR) is possible.
Antibodies to the HIV at 90-95 % of the infected appear within 3 months after
infection (the earliest term - 2 weeks), at 5-9 % - within 6 months, at 0,5-1 % - in later
terms.
Nonspecific diagnostics. Be investigated of cellular immunity, first of all -
definition of absolute and relative maintenance of CD4-lymphocytes (helpers), CD8-
lymphocytes (suppressors) and their correlation.
At the adult patients who are taking place in a latent stage of disease, level of
СD4-lymphocytes usually exceeds 0,5*109/l. Proof decrease of CD4 is lower than this
level results in transition of HIV-infection in a stage 4А, is lower 0,35*109/l - in a stage
4B, lower 0,2*109/l - in a stage 4C. Decrease of a parameter below 0,05*109/l, down to
full absence is typical for a stage 5. Decrease of quantity of CD4 - cells, as a rule,
outstrips clinical progressing disease a little. On the other hand, sometimes patients with
very low quantity of CD4-cells (even less 0,1*109/l) live within several years.

Treatment
Basis of treatment - purpose of antiretroviral therapy under clinical and laboratory
indications (the control of level of CD4-lymphocytes and concentration in blood RNA of
the HIV - i.e. virus loading is desirable). Antiretroviral preparations (Azidotymidin,
Phosphazid, Didanosid, Lamivudin, Hivid etc.) have various mechanisms of action and
are applied in combinations, in various circuits - depending on a stage of HIV-infection,
the immune status and virus loading.
The unconditional indication to the beginning of antiretroviral therapy are initial
clinical manifestations of the disease (acute HIV-infection 2B, 2C) and a stage of
secondary diseases (4B, 4C) in a phase of clinical progressing.
Laboratory indications to realization of antiretroviral therapy are the decrease of
level of CD4-lymphocytes less than 0,3*109/l (at children till 6 years - individually) or
the increase of concentration of RNA of the HIV in blood, so-called “virus loading”:
• at children in the age of about 30 months - more than 100000 copies in ml,
• at children in the age of than 30 months - more than 20000 copies in ml,
• at adults - more than 60000 copies in ml of blood (parameters are not taken
into account in case of recent inflammatory disease or an inoculation).
If laboratory indications of such level are revealed for the first time for the decision of a
question on expediency of the beginning of antiretroviral therapy will carry out repeated
research with an interval not less than 4 weeks.
To children till 1 year with finally made diagnosis HIV-infection antiretroviral
therapy is appointed irrespective of the clinical, immunological and virologic data. In
stages 2A, 2B and 3 at absence of immunodeficiency and at moderate
immunodeficiency bitherapy to two inhibitors of return transcriptase is carried out.
Treatment of opportunistic infections will be carried out by the appropriate
preparations, after liquidation of acute manifestations of the disease supporting therapy -
with the purpose of chemoprophylaxis of relapses is appointed.
Dispensary supervision over the HIV-infected persons is carried out to a
territorial attribute by the doctor’s consulting room of infectious diseases, and at its
absence - the local doctor. Children and teenagers are observed in children's consultation
at the pediatrist. At the request of the patient dispensary supervision can be carried out
only in the regional Centre on prophylaxis and struggle about AIDS.
At statement of the patient on the account his initial inspection - with the purpose
of confirmation of the diagnosis, an establishment of a stage of the disease, revealing of
secondary and accompanying diseases will be carried out.
According to the current legislation, initial inspection of the patient and in case of
revealing the HIV-infection - the subsequent treatment and supervision should be carried
out from his voluntary informed consent. The pregnant woman has the right to refuse
inspection on the HIV-infection, and in case of its revealing - from realization of
chemoprophylaxis of infection of a fetus, the further supervision and inspection of the
child. Refusal should be made out documentary in an out-patient card. At detection at
the pregnant woman of the HIV-infection she should be acquainted with conditions of
realization of chemoprophylaxis of transfers of the HIV from her to the child during
pregnancy and labor. In case of the consent with conditions the woman makes out “the
Informed consent”, as the official medical and legal document - with own hand, with the
signature; the doctor also signs this document.

REALIZATION OF THE LESSON


The purpose is to learn to diagnose the HIV-infection on the clinic-
epidemiological data to make the plan of inspection for revealing of the HIV-
INFECTED, to know principles of treatment of patients.

Control questions
1. Etiology of the HIV.
2. Name sources of the HIV-infection.
3. List ways of transfer of the HIV-infection.
4. List clinical stages of the HIV on V.I.Pokrovsky (2001г).
5. List variants of current of initial manifestations of the HIV
6. List clinical variants of the 4 stage of secondary diseases of the HIV-infection.
7. Name methods of laboratory diagnostics of the HIV-infections.
8. List antiviral preparations used for treatment of the HIV.
9. Name the clinic-laboratory data at the HIV for purpose of antiviral therapy.
10. Name ways of the prophylaxis of the HIV.

The test.

1. Occurrence of opportunistic infections at the HIV is caused by:


1. Disturbance of "recognition" of alien antigens by system of macrophages
2. Disturbance of process of antigenogenesis
3. Decrease of level of Т-helpers
4. Decrease) of a level of secretory antibodies
5. Decrease of phagocytic activity of phagocytes
2. Immunodeficiency at the HIV-infection is accompanied by:
1. Decrease of level of Т4-lymphocytes
2. The high level of the Circulating immune complexes
3. Decrease of quantity of the Circulating immune complexes
4. The high level of immunoglobulins of all classes
5. Decrease of levels of immunoglobulins
3. The termination of the incubatory period at the HIV-infection associates with:
1. Rise in temperature of a body
2. Increase of lymph nodes
3. Occurrence of candidosis of mucous membranes and integuments
4. Occurrence of antibodies to the HIV
5. Sharp weight loss
4. Acute retroviral (mononucleosoliked) syndrome includes:
1. Fever
2. Polylymphoadenopathy
3. Erytematous-mononuclear rash
4. Stomatitis, esophagitis
5. Ulcers on mucous membranes of genitals
5. The phase A of stages of secondary diseases:
1. Superficial lesions of a skin and mucous membranes by fungoid flora
2. Superficial lesions of a skin and mucous membranes by bacterial flora
3. Superficial lesions of a skin and mucous membranes by viral flora
4. Deficiency of weight of a body more than 10 % of initial
5. Loss of weight of a body less than 10 % of initial
6. The phase B of a stage of secondary diseases:
1. Recidivating lesion of a skin and mucous membranes by fungoid, bacterial and
(or) a virus nature
2. Proof lesion of a skin and mucous membranes by fungoid, bacterial and (or) a
virus nature
3. Proof diarrhea more than 1 month
4. Proof fever more than 1 month
5. Located Kaposhi’s sarcoma
7. The final diagnosis of the HIV-infection can be made:
1. To clinical attributes
2. At revealing of antibodies to the HIV in the IFA
3. At revealing of antibodies to the HIV in the IFA and in immunoblotting
4. At revealing of proof lymphadenopathy
5. At revealing of generalized Kaposhi’s sarcomas
8. The clinical attributes - indicators indicating necessity of inspection on the HIV-
infection:
1. Causeless diarrhea during 1 month and more
2. Proof fever during 1 month and more
3. Constant night sweats
4. Loss of weight
5. Bilateral polylymphoadenopathy more than 2 groups of lymph nodes (behind
exception of inguinal) more than 2 month
9. It is necessary to suspect the HIV-infection, if comes to light:
1. Histologically confirmed Kaposhi’s sarcoma at persons who are older than 60
years
2. Toxoplasmosis of a brain
3. Tuberculosis (typical and/or atypical) of any localization
4. Chronic lymphoid pneumonia with lymphoid infiltration at persons who are
older than 13 years
5. Malignant lymphoma
10. Treatment of the HIV-infection includes purpose of:
1. Antiretroviral preparations
2. Antibacterial preparations
3. Antimycotic preparations
4. Cytoctatics
5. Immunomodulators

At discussion of a theme of the lesson students solve clinical problems. Write in


writing-books the clinical diagnosis in view of a stage of disease, the plan of laboratory
diagnostics, purpose of treatment of antiviral and pathogenetic therapy.

PROBLEM
In infectious hospital patient P., 28 years, with complaints to a high body
temperature (up to 40°С), a headache, periodic vomiting, a dyspnea has arrived. At
survey: a condition is heavy; he is exhausted, pale, there is acrocyanosis. Peripheral
lymphatic nodes are increased about 1-1,5 sm, mainly in a cervical area, they are dense,
mobile, painless. There is a dyspnea (28 in one minute), at auscultation there is harsh
breathing. Tones of heart are muffled. Pulse is 120 in one minute, weak filling. The liver
comes forward from under the right costal arch on 2,5 sm, the spleen is palpated. The
patient is disoriented in a place, time, the own person. It is revealed right-hand
hemiparesis. Generalized spasms are periodically arisen. There are no meningeal
symptoms. The relative, accompanied the patient, has told, that patient consists on the
account concerning the HIV-infection during 3 years. Deterioration of a condition has
come about 3 weeks back when headaches and high temperature, and then - vomiting,
spasms, disorientation have appeared.
At laboratory research in the immune status significant decrease of quantity of
CD4-lymphocytes (up to 50 cells in mcl) is marked. At research of blood there are
anemia and leucopenia. At realization of computer tomography of a brain in a cortex of
a brain it is revealed a little of annular condensation surrounded by an edematous tissue.

1. To what deterioration of a condition of the patient by the HIV-infection can be


connected?
2. Appoint inspection.
3. What tactics of conducting of the patient?
4. The prognosis.

PROBLEM
Patient B., 19 years, the student. He has addressed to the doctor of a polyclinic in
connection with detection within 3-4 months of the increased lymph nodes on a neck.
Objectively: a body temperature is normal. A condition is satisfactory. A skin is of usual
coloring, without a rash. There are traces of intravenous injections on hands. Back-
cervical, supraclavicular and ulnar lymph nodes are increased up to 1 sm, axillary - up to
1,5 sm in diameter; they are of densely - elastic consistence. They are painless. By the
side of internal organs pathology is not revealed. At ultrasonic research of organs of an
abdominal cavity and at radiography of organs of a chest the increase of visceral lymph
nodes is not revealed.
1. What is the provisional diagnosis? Present its substantiation.
2. The plan of inspection.
3. Give the recommendation to the patient.

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