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HIV and Tuberculosis

Session Objectives
• Explain the relationship between HIV & TB
• Describe the epidemiology of HIV & TB on a
global and Indian scale
• List the manifestations of TB in different
stages of HIV
• Determine the appropriate time to initiate a
regimen for treatment of TB in HIV-positive
patients
• Describe how to appropriately manage ARV
treatment for a co-infected patient

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Risk of TB in HIV Patients
HIV patients are at an
increased risk of:
– Acquiring latent TB 70%
60%
– Developing active TB 50% 60%
once infected with M. 40%
Lifetim
tuberculosis 30% e Risk
– Becoming re-infected 20% of TB
10%
with a second strain of 0%
10%
TB
PPD +/H I V -negative PPD +/H I V +
– Relapsing after
stopping treatment

Source: NACO, ND

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HIV & TB: Global Scenario

HIV
TB Infection
Infection 39.5 million
14
Million

TB and HIV co-infection 13 million


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HIV & TB: Indian
Scenario
TB HIV
• 40% population • HIV prevalence is
infected <1 %
• 1.8 million new TB • 50-60% HIV infected
cases annually are expected to
• Incidence of TB is develop TB
higher in northern • Prevalence of HIV
states higher in 6 states
• Up to 5% of TB • TB is leading cause of
patients are HIV deaths in people with
positive HIV

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Extra-Pulmonary
Tuberculosis
CD4 CELLS
CD4 CELLS
Pulmonary
500
> 300 2
tuberculosis

400 Lymphatic, serous


tuberculosis

201-300 8 300 Tuberculous


meningitis
Disseminated
200
tuberculosis
101-200 20
100

0
0-100 47

0 10 20 30 40 50 Duration of HIV infection


Mycobacteremia
Source: De Cock KM et al, J Am Med Assoc, 1992

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Early and Late Stages of HIV
Infection
Features Stage of HIV Infection
Early Late
Clinical Often resembles Often resembles primary
Presentation Post-primary TB TB
(Adult Type)

Sputum Smear Often positive Often negative


Result
Chest X-ray Often shows •Atypical presentation,
Appearance cavities often infiltrates lower
lung-field lesions, intra-
thoracic lymph nodes &
infrequent cavities
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Case Study 1
• A 25 year-old man presents
with a PUO of 3 months
duration
• On examination he is febrile
Temp=102 F
• Has large nodes in the
axillary and cervical regions
• Abdomen examination
shows hepatosplenomegaly
• Respiratory system reveals
crackles, diffusely
bilaterally

Courtesy of GHTM, Chennai, 2004

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Factors Affecting Diagnosis
of TB in HIV-positive
Patients
• Fear of stigma and discrimination
• AFB smear microscopy
• Degree of immunosuppression
• Atypical CXR findings (may be negative)
• Tuberculin Anergy
• Co-infected patients have:
– Higher proportion of sputum smear negative
pulmonary disease (22- 64%)
– Higher proportion of extra pulmonary disease

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Radiological Features of TB

Courtesy of: GHTM, Chennai, 2004


Pulmonary TB: Typical Primary TB
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Radiological Features of TB
(2)

Courtesy of:GHTM, Chennai, 2004


HILAR / MEDIASTINAL TB
PROGRESSIVE TB
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Radiological Features of TB
(3)

Courtesy of: GHTM, Chennai, 2004


ATYPICAL TB LOWER LUNG-FIELD TB
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Radiological Features of TB
(3)

Courtesy of: GHTM, Chennai, 2004

MILIARY / NODULAR TB DISSEMINATED TB


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Components of Treatment
Management in HIV-TB
Patients
• Anti-TB drugs per RNTCP schedule
• Evaluate for OIs
• Start cotrimoxazole prophylaxis
• Appropriate nutrition
• Screening of other family member for
HIV and TB
• Screen for ATT and ART side effects
• Start ART if appropriate

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Treatment Outcome

After
6
Months
Courtesy of: GHTM, Chennai, 2004

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HIV & TB: Treatment
• Duration of treatment: 6 months (2HREZ/4HR)
• Rifampicin contra-indicated with PI/nevirapine
containing HAART regimens
• Possible options for ART in patients with active
TB:
– Defer ART until TB treatment is completed
– Defer ART until the ‘continuation phase' of
treatment for TB, and use HE as continuation.
– Treat TB with RIF containing regimen and use
Efavirenz + 2 NRTIs

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Managing TB and ART
• Need experienced physician
• Adequate training
• Patient needs to get adjusted to the
diagnosis and treatment of TB in HIV
– Drug Interactions
– Issue of adherence
– Side effects and drug complications
– Problems of Immune Reconstitution
• Programmatic Issues

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Initiation of ART for Patients
With TB
Reasons to start ART
• Decrease morbidity and mortality related to HIV/AIDS
Reasons to delay ART
• Overlapping side effects from ART and anti-TB therapy
• Complex drug-drug interactions
• Immune reconstitution inflammatory syndrome
(paradoxical reactions)
• Difficulties with adherence to multiple medications
• Pill burden

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First Line ARV Treatment in
India

ZIDOVUDINE
NEVIRAPINE
OR + LAMIVUDINE + OR

STAVUDINE
EFAVIRENZ

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TB and ARV Treatment
CD4 cell count Timing of ART in relation to ART
start of TB treatment recommendation
(cells/ mm3)
s
CD4 < 200 Start ATT first.Start ART as Recommend ART.
soon as TB treatment is (ii)
tolerated (between 2 weeks
and 2 months)(i)
EFV containing
regimens (iii)
CD4 between Start ATT first.Start ART Recommend ART
200-350 after 8 weeks of ATT.(ie. (vi)
completion of TB intensive
phase)
CD4 > 350 Start ATT first.Re-evaluate Defer ART (iv)
patient for ART at 8 weeks
and at end of TB treatment
CD4 not Start ART between 2 and 8 Recommend ART
available weeks after ATT initiation (i,v) Source: NACO, ND
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TB and ARV Treatment:

Drug Interactions
• Rifampicins stimulate cytochrome P450 liver
enzyme system that metabolizes PIs and
NNRTIs
• Protease inhibitors and NNRTIs can enhance or
inhibit this system leading to altered blood
levels of Rifampicin
• Rifampicin significantly reduced bioavailability
of Nevirapine and the C min to sub-therapeutic
levels in 62% of patients

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Case Study 2: Treatment
• HIV-positive patient
presents in outpatient
dept.
• Associated conditions:
– Oral candidiasis
– Sinusitis
– Scabies
• CD4 count: 362 cells
• Hb: 11.6
Courtesy of: GHTM, Chennai, 2004
• Body weight: 62 Kg
Chest X-ray: PT
Sputum smear: ++

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Case Study 3: Treatment
• HIV-positive patient
hospitalized
• Associated
conditions:
– Oro-oesophageal
candidiasis
– Molluscum
Contagiosum
• CD4 count: 186
Courtesy of GHTM, Chennai, 2004
• Hb: 7.5
Chest X-ray: PT
• Body weight: 38 Kg
Sputum smear: negative
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Case Study 4: Treatment
• HIV-positive patient
hospitalized
• Associated conditions:
– Oro-oesophageal
candidiasis
– Cryptococcosis
• CD4 count: 48 cells
• Hb: 8.5
• Body weight: 41 Kg
Courtesy of GHTM, Chennai, 2004
• Pregnant: 3 months
Chest X-ray: PT
Sputum smear: one smear +
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Immune Reconstitution
Inflammatory Syndrome
• Can happen with any antiretroviral regimen
• Mean onset of symptoms is 2 weeks
• Mean duration of symptoms is 3 weeks
• Most common symptoms include fever,
cervical lymphadenopathy, Intrathoracic
lymphadenopathy
• Associated with restoration of tuberculosis
reactivity

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Immune Reconstitution TB
• Master AB, 7 years
• HIV-positive presenting with
fever, loss of appetite, loss
of weight and oral
candidiasis
• Mantoux Test: 0 mm.
• Sputum Smear AFB:
Negative
• CD4 COUNT: 84 Cells (4%)
• Treatment: 2HRZ + 4HR

Courtesy of: GHTM, Chennai, 2004

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Immune Reconstitution TB
(2)

Courtesy of: GHTM, Chennai, 2004

PRE-TREATMENT AFTER 2 HRZ

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Immune Reconstitution TB
(3)

Courtesy of: GHTM, Chennai, 2004

Third week after


AFTER 2 HRZ
ART (d4T+3TC+EFV)
- IRS
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Immune Reconstitution TB
(4)

Courtesy of GHTM, Chennai, 2005

Third week after After treating IRS


ART (d4T+3TC+EFV)
- IRS
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IR-TB: Pleural Effusion

Courtesy of: GHTM, Chennai, 2005

Just before ART Fourth Month after


ART
(ART:
d4T+LAM+NEV)
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HIV & TB - Prophylaxis:
Challenges
• Difficulties in ensuring adherence
• Efficacious but inefficient
• Rare adverse drug events
• Ensuring certainty to exclude active
tuberculosis

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Challenges to Linking TB
and AIDS Activities
• Increased stigma in linking 2 diseases
• Adds more activities to overburdened TB
programmes
• Increase in HIV care may promote creation of
parallel systems for treating TB patients and
weaken National TB Programmes
• Differences in resources
• Interest in providing ART may overshadow
interest in strengthening NTP

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Key Points
• TB is the most common opportunistic
infection in patients with HIV in India
• HIV–TB co-infection has to be treated with
ATT and ART as per NACO guidelines for
better outcome
• INH prophylaxis is not indicated as of
today as per NACO
• IRIS TB is very common in patients who
were on ATT and then started on ART

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