tuberculosis in the age of hiv
TRANSCRIPT
-
8/2/2019 Tuberculosis in the Age of Hiv
1/33
TUBERCULOSIS IN THE AGEOF HIV
Dr. Terry Baker
Physician
National Chest Hospital
-
8/2/2019 Tuberculosis in the Age of Hiv
2/33
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.
-
8/2/2019 Tuberculosis in the Age of Hiv
3/33
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
-
8/2/2019 Tuberculosis in the Age of Hiv
4/33
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
-
8/2/2019 Tuberculosis in the Age of Hiv
5/33
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
-
8/2/2019 Tuberculosis in the Age of Hiv
6/33
Tuberculosis & HIV
Caribbean Epidemiology Centre (CAREC/PAHO/WHO)
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
-
8/2/2019 Tuberculosis in the Age of Hiv
7/33
Tuberculosis & HIV
Caribbean Epidemiology Centre (CAREC/PAHO/WHO)
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
-
8/2/2019 Tuberculosis in the Age of Hiv
8/33
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%
-
8/2/2019 Tuberculosis in the Age of Hiv
9/33
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
-
8/2/2019 Tuberculosis in the Age of Hiv
10/33
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 ).
-
8/2/2019 Tuberculosis in the Age of Hiv
11/33
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
-
8/2/2019 Tuberculosis in the Age of Hiv
12/33
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
-
8/2/2019 Tuberculosis in the Age of Hiv
13/33
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.
-
8/2/2019 Tuberculosis in the Age of Hiv
14/33
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.
-
8/2/2019 Tuberculosis in the Age of Hiv
15/33
CLINICAL PRESENTATION
Dependent on degree ofimmunosuppression.
Presentation varied. Extra-pulmonary TB, particularly
lymph node involvement morecommon.
-
8/2/2019 Tuberculosis in the Age of Hiv
16/33
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
-
8/2/2019 Tuberculosis in the Age of Hiv
17/33
Central bronchiectasis and LULobe cavity
-
8/2/2019 Tuberculosis in the Age of Hiv
18/33
RULobe abscess
-
8/2/2019 Tuberculosis in the Age of Hiv
19/33
LULobe pneumonia with air bronchograms
-
8/2/2019 Tuberculosis in the Age of Hiv
20/33
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.
-
8/2/2019 Tuberculosis in the Age of Hiv
21/33
TREATMENT OF TUBERCULOSIS
First line drugs- Rifampin, Isoniazid,Pyrazinamide, Ethambutol,Streptomycin.
Rifampin- most important and mostpotent.
Second line drugs- Quinolones,
Amikacin, Capreomycin.
-
8/2/2019 Tuberculosis in the Age of Hiv
22/33
ANTI-RETROVIRAL THERAPY
HAART dramatic improvement inprognosis for HIV- infected patients.
Drug interactions complicate themanagement of tuberculosis.
Interaction is mainly with theRifamycins.
-
8/2/2019 Tuberculosis in the Age of Hiv
23/33
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.
-
8/2/2019 Tuberculosis in the Age of Hiv
24/33
PHARMACOKINETICS OF ARVS AND
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
-
8/2/2019 Tuberculosis in the Age of Hiv
25/33
PHARMACOKINETICS OF ARVS AND
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.
-
8/2/2019 Tuberculosis in the Age of Hiv
26/33
PHARMACOKINETICS OF ARVS AND
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.
-
8/2/2019 Tuberculosis in the Age of Hiv
27/33
PHARMACOKINETICS OF ARVS AND
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.
-
8/2/2019 Tuberculosis in the Age of Hiv
28/33
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.
-
8/2/2019 Tuberculosis in the Age of Hiv
29/33
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
-
8/2/2019 Tuberculosis in the Age of Hiv
30/33
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
-
8/2/2019 Tuberculosis in the Age of Hiv
31/33
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.
-
8/2/2019 Tuberculosis in the Age of Hiv
32/33
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
-
8/2/2019 Tuberculosis in the Age of Hiv
33/33
Thank you