12 HIV and TB

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HIV and Tuberculosis

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HIV and Tuberculosis 2

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-positivepatients

Describe how to appropriately manage ARVtreatment for a co-infected patient

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Risk of TB in HIV Patients

HIV patients are at anincreased risk of:

Acquiring latent TB

Developing active TBonce infected with M.tuberculosis

Becoming re-infectedwith a second strain ofTB

Relapsing afterstopping treatment

1 0

6 0

0%

1 0%

2 0%

3 0%

4 0%

5 0%

6 0%

7 0%

PPD +/H IV -negative PPD +/H IV +

Source: NACO, ND

Lifetime Risk

of TB

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HIV & TB: Global Scenario

HIVInfection

39.5 million

TB

Infection14

Million

TB and HIV co-infection 13 million

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HIV & TB: IndianScenario

TB 40% population

infected

1.8 million new TBcases annually

Incidence of TB ishigher in northernstates

Up to 5% of TBpatients are HIVpositive

HIV HIV prevalence is

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4

2

8

2

0 10 2 0 3 0 4 0 50

0 - 1 0 0

1 0 1 - 2 0 0

2 0 1 - 3 0 0

> 3 0 0

Mycobacteremia

CD4 CELLS

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

Extra-PulmonaryTuberculosis

Duration of HIV infection

0

100

200

300

400

500 Pulmonarytuberculosis

Lymphatic, serous

tuberculosis

Tuberculous

meningitis

Disseminated

tuberculosis

CD4 CELLS

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Early and Late Stages of HIVInfection

Features Stage of HIV Infection

Early Late

ClinicalPresentation

Often resemblesPost-primary TB(Adult Type)

Often resembles primaryTB

Sputum SmearResult

Often positive Often negative

Chest X-rayAppearance

Often showscavities

Atypical presentation,often infiltrates lowerlung-field lesions, intra-thoracic lymph nodes &infrequent cavities

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Case Study 1

A 25 year-old man presentswith a PUO of 3 monthsduration

On examination he is febrileTemp=102 F

Has large nodes in theaxillary and cervical regions

Abdomen examinationshows hepatosplenomegaly

Respiratory system revealscrackles, diffuselybilaterally

Courtesy of GHTM, Chennai, 2004

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Factors Affecting Diagnosisof 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 negativepulmonary disease (22- 64%)

Higher proportion of extra pulmonary disease

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Pulmonary TB: Typical Primary TB

Radiological Features of TB

Courtesy of: GHTM, Chennai, 2004

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HILAR / MEDIASTINAL TB

Radiological Features of TB(2)

PROGRESSIVE TB

Courtesy of:GHTM, Chennai, 2004

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ATYPICAL TB LOWER LUNG-FIELD TB


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MILIARY / NODULAR TB DISSEMINATED TB



C t f T t t

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Components of TreatmentManagement in HIV-TB

Patients Anti-TB drugs per RNTCP schedule Evaluate for OIs

Start cotrimoxazole prophylaxis

Appropriate nutrition

Screening of other family member forHIV and TB

Screen for ATT and ART side effects

Start ART if appropriate

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Treatment Outcome

After6

Months


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HIV & TB: Treatment

Duration of treatment: 6 months (2HREZ/4HR)

Rifampicin contra-indicated with PI/nevirapinecontaining HAART regimens

Possible options for ART in patients with active

TB: Defer ART until TB treatment is completed

Defer ART until the continuation phase' oftreatment for TB, and use HE as continuation.

Treat TB with RIF containing regimen and useEfavirenz + 2 NRTIs

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Managing TB and ART

Need experienced physician Adequate training

Patient needs to get adjusted to thediagnosis 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 PatientsWith 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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ZIDOVUDINENEVIRAPINE

OR + LAMIVUDINE + OR

STAVUDINE

EFAVIRENZ

First Line ARV Treatment inIndia

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TB and ARV TreatmentCD4 cell count

(cells/ mm3)

Timing of ART in relation tostart of TB treatment

ARTrecommendation

s

CD4 < 200 Start ATT first.Start ART assoon as TB treatment istolerated (between 2 weeksand 2 months)(i)

Recommend ART.(ii)

EFV containing

regimens (iii)CD4 between200-350

Start ATT first.Start ARTafter 8 weeks of ATT.(ie.completion of TB intensivephase)

Recommend ART(vi)

CD4 > 350 Start ATT first.Re-evaluatepatient for ART at 8 weeksand at end of TB treatment

Defer ART (iv)

CD4 notavailable

Start ART between 2 and 8weeks after ATT initiation

Recommend ART(i,v) Source: NACO, ND

TB and ARV Treatment

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TB and ARV Treatment:

Drug Interactions Rifampicins stimulate cytochrome P450 liverenzyme system that metabolizes PIs andNNRTIs

Protease inhibitors and NNRTIs can enhance orinhibit this system leading to altered bloodlevels of Rifampicin

Rifampicin significantly reduced bioavailability

of Nevirapine and the C min to sub-therapeuticlevels in 62% of patients

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Case Study 2: Treatment

HIV-positive patientpresents in outpatientdept.

Associated conditions: Oral candidiasis

Sinusitis

Scabies

CD4 count: 362 cells

Hb: 11.6

Body weight: 62 KgChest X-ray: PTSputum smear: ++


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HIV-positive patienthospitalized

Associatedconditions:

Oro-oesophagealcandidiasis

MolluscumContagiosum

CD4 count: 186 Hb: 7.5

Body weight: 38 KgChest X-ray: PTSputum smear: negative



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HIV-positive patienthospitalized

Associated conditions: Oro-oesophageal

candidiasis Cryptococcosis

CD4 count: 48 cells

Hb: 8.5

Body weight: 41 Kg Pregnant: 3 months

hest X-ray: PTputum smear: one smear +



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Immune ReconstitutionInflammatory 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, Intrathoraciclymphadenopathy

Associated with restoration of tuberculosisreactivity

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Immune Reconstitution TB

Master AB, 7 years

HIV-positive presenting withfever, loss of appetite, lossof weight and oralcandidiasis

Mantoux Test: 0 mm. Sputum Smear AFB:

Negative

CD4 COUNT: 84 Cells (4%)

Treatment: 2HRZ + 4HR


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PRE-TREATMENT AFTER 2 HRZ

Immune Reconstitution TB(2)


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Third week afterART (d4T+3TC+EFV)

- IRS

AFTER 2 HRZ



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Third week afterART (d4T+3TC+EFV)

- IRS


After treating IRS


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Just before ART Fourth Month afterART(ART:

d4T+LAM+NEV)

IR-TB: Pleural Effusion


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HIV & TB - Prophylaxis:Challenges

Difficulties in ensuring adherence

Efficacious but inefficient

Rare adverse drug events

Ensuring certainty to exclude activetuberculosis

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Challenges to Linking TBand AIDS Activities

Increased stigma in linking 2 diseases

Adds more activities to overburdened TBprogrammes

Increase in HIV care may promote creation ofparallel systems for treating TB patients andweaken National TB Programmes

Differences in resources

Interest in providing ART may overshadowinterest in strengthening NTP

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Key PointsTB is the most common opportunistic

infection in patients with HIV in India

HIVTB co-infection has to be treated withATT 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 whowere on ATT and then started on ART

12 HIV and TB

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