Tuberculosis in the Age of Hiv

8/2/2019 Tuberculosis in the Age of Hiv

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TUBERCULOSIS IN THE AGEOF HIV

Dr. Terry Baker

Physician

National Chest Hospital


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THE PROBLEM

Global epidemic of HIV infection.

HIV- infected persons highly susceptibleto M. tuberculosis disease.

Impact of HIV epidemic and TB greatestin the developing world.

33% HIV infected population co-infectedwith TB.

TB - the most common opportunistic lunginfection.


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Tuberculosis & HIV

Region Adults & ChildrenAdult living with HIV/AIDS

Prevalence Rate

Sub-Saharan 23.3 million8.0 %

Latin America 1.3 million0.57 %

Caribbean 360,000

1.96%Western Europe 520,000

0.25%

North America 920,0000.56%

World HIV/AIDS Statistics by Region, December 1999


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New AIDS Cases Per YearPer 100,000 Population

0

5

10

15

20

25

30

35

90 91 92 93 94 95 96 2000

Latin America

North America

Caribbean


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Tuberculosis & HIV

Caribbean Epidemiology Centre (CAREC/PAHO/WHO)

Reported AIDS Cases in Barbados 1984 - 1998

29

2124

15

40

61

78 78

90

119

95

130

113

168

(20)

-

20

40

60

80

100

120

140

160

180

1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998

Years

NumberofC

ases

n


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Tuberculosis & HIV


Reported AIDS Cases in Trinidad & Tobago 1983 - 1999

8 1352

83115

166 164

198

249

298 302

264

399

468

408

459

677

(100)

-

100

200

300

400

500

600

700

800

1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999

Years

NumberofCa

ses


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Tuberculosis & HIV


Reported AIDS Cases in Jamaica 1982 - 1999

1 0 1 633 30

63 62

133

99

236

359

505

527

609645

892

30

100

200

300

400

500

600

700

800

900

1000

1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999

Years

Numberof

Cases


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CO-INFECTION RATES

Jamaica

YEAR No. Tb Cases No Tb/HIV Percent co -

infected

1994 109 5 4.6%

1995 109 7 6.4%

1996 121 14 11.6%

1997 118 14 11.9%

1998 121 10 8.3%

1999 108 8 7.4%

2000 124 18 14.5%


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CO-INFECTION RATES

Tb/ HIV Co-infected Cases, Jamaica 1991-2000

0.00%

2.00%

4.00%

6.00%

8.00%

10.00%

12.00%

14.00%

16.00%

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

Tb/ HIV


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TUBERCULOSIS AND HIV

Implications: two-fold

One epidemic (i.e. HIV) can potentiallydrive a second epidemic (i.e.Tuberculosis).

Intersection of both epidemics couldpotentially spawn a third:

i.e. Multiple Drug Resistant Tuberculosis( MDRTb ).


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Tuberculosis & HIV

MDRTb :

Tb resistant to conventional therapy:

Isoniazid ( INH ) and Rifampicin

Treatment regimen is six-seven drugs

Mortality remains in excess of 80 %

Has the potential to infect both HIV and non-HIV populations


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Tuberculosis & HIV

Conversion ( to active Tb disease afterinfection ) :

Non-HIV : following infection, conversionis 5-10% over a lifetime

HIV: conversion is 5-10%per year


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PATHOGENESIS OF CO-INFECTION

HIV-infected persons are at risk forprimary or reactivated TB, and forsecond episodes of TB.

Reduced T1 response. CD 4+ lymphocytes unable to

produce alpha- interferon.

Alpha-interferon central toanti- mycobacterial immunedefenses.


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PATHOGENESIS OF CO-INFECTION

Presence of TB up-regulatesretroviral replication.

TB infection producesproinflammatory cytokines.

Risk of death 2x greater in HIV-infected patients with TB.

Death due to progression of HIVand not TB.


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CLINICAL PRESENTATION

Dependent on degree ofimmunosuppression.

Presentation varied. Extra-pulmonary TB, particularly

lymph node involvement morecommon.


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Diagnosis

History- Malaise, weight loss, fever,cough, haemoptysis

Physical Examination

Laboratory Examinations AFB smear,lymph node biopsy, BAL, pleural biopsy,cultures

Chest X-ray findings variable

? Mantoux Test ? Rapid diagnostic tests- identifies TB RNA

or DNA


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Central bronchiectasis and LULobe cavity


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RULobe abscess


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LULobe pneumonia with air bronchograms


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HIV AND THE TREATMENT OF

TUBERCULOSIS

Six months vs. Nine months Clinical or bacteriological delayed

response- Longer therapy.

Lack of adherence to therapy mostimportant impediment to cure.

Higher risk of MDRTb Greater risk of prolonged disease.

Strong public health services (DOT)improve outcome.


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TREATMENT OF TUBERCULOSIS

First line drugs- Rifampin, Isoniazid,Pyrazinamide, Ethambutol,Streptomycin.

Rifampin- most important and mostpotent.

Second line drugs- Quinolones,

Amikacin, Capreomycin.


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ANTI-RETROVIRAL THERAPY

HAART dramatic improvement inprognosis for HIV- infected patients.

Drug interactions complicate themanagement of tuberculosis.

Interaction is mainly with theRifamycins.


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PHARMACOKINETICS OF ARVS AND

ANTI-TB DRUGS

Rifamycins induce CYp450, decreasingserum levels of the protease inhibitors.

Protease inhibitors inhibit CYp450system, increasing serum rifamycinslevels to possibly toxic levels.

Net effect is that protease inhibitors maylose their efficacy and rifamycintoxicity may be increased.


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ANTI-TB DRUGS

q Rifampicin is the most potent inducer CYp450

q Rifabutin is the least potent inducer and maybe substituted for rifampicin.

q Clinical trials have demonstrated comparablesafety and efficacy.

q The dose of rifabutin should be reduced from300 to 150 mg daily in pts. on Protease

Inhibitors.

q CDC. Report of the NIH panel to define principles of therapy of HIV infection and guidelines forthe use of antiretroviral agents in HIV-infected adults and adolescents. MMWR 1998; 48 ( No.RR-5): 1 -63


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ANTI-TB DRUGS

Protease inhibitors that can beconcurrently administered withRifabutin are Indinavir and Nelfinavir.

More recently: Lopinavir, Amprenavir

can be given, but with adjusted dosesof Rifabutin: 150mg daily.


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ANTI-TB DRUGS

NNRTIs - may inhibit or induce p450.

Efavirenz - rifabutin dosage should beincreased.

Nevirapine can be used without dosageadjustment.

NRTIs- Rifamycins can be used withoutdose adjustment.


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ANTI-TB DRUGS

Regimens with rifamycins are shorter,have faster conversion and lowerrelapse rates than those without.

HIV-infected TB patients treated withoutrifamycins may have a higher risk ofdying.


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CONTROVERSIES

? Continuation of anti-retroviraltherapy during Anti-TB therapy.

? Anti-TB regimens not including a

rifamycin. ? When to initiate anti-retroviral

therapy in HIV-infected TB patient.

? Risk of paradoxical reactions andglucocorticoid therapy. ? Malabsorption of anti-TB meds.


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PARADOXICAL REACTIONS

q Up to 1/3 of co-infected patients on anti-Tbmeds will experience paradoxical worseningwhen antiretroviral therapy is introduced.

q The clinical manifestation is usually fever,intrathoracic and cervical lymphadenopathy,pleural effusions and/or skin lesions.

q Usually occurs within 15 days of initiation of

therapy.Paradoxical worsening of Tb following antiretroviral therapy in pts with AIDS Am. J Respir CritCare Med 1998; Nariita M et al

Smith H. Paradoxical responses during the chemotherapy of tuberculosis. J. Infect Dis 1987; 15:

1-3


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PARADOXICAL REACTIONS

q This appears to be associated with a markeddrop in HIV viral load even though theperipheral CD4+ remains abnormally reduced

q Paradoxical reactions have been attributed tostrengthening of the hosts delayedhypersensitivity response, a decrease in

suppressor mechanisms and / or anincreased exposure to mycobacterial antigensfollowing bactericidal TB chemotherapy


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CHEMOPROPHYLAXIS FOR TB

Need to exclude active disease. Recommended for recent close

contact with potentially infectious

persons with TB. ? Positive Mantoux test and need

for prophylaxis.

Isoniazid for nine months ORRifampin/ Rifabutin & Pyrazinamidefor two months.


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THE FUTURE

Decline in the number of TB casesin persons with HIV due to betteravailability of ARV.

Development of new anti-Tb andARV with fewer drug interactionsessential to reduce morbidity and

mortality. Strengthened Public Health Services


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Thank you

Tuberculosis in the Age of Hiv

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