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MDR-TB and HIV: how big is the problem and what are we going to do about it Matteo Zignol, Abigail Wright, Brian Williams Stop TB Department World Health.

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Presentation on theme: "MDR-TB and HIV: how big is the problem and what are we going to do about it Matteo Zignol, Abigail Wright, Brian Williams Stop TB Department World Health."— Presentation transcript:

1 MDR-TB and HIV: how big is the problem and what are we going to do about it Matteo Zignol, Abigail Wright, Brian Williams Stop TB Department World Health Organization - Geneva TB/HIV Research Priorities in Resource-Limited Settings 14 February 2005 Geneva

2 MDR-TB and HIV 1.What do we know 2.What do we need to know 3.What has to be done in order to fill the knowledge gap 4.What to do in the meantime

3 Epidemiology in institutions Majority of the studies reviewed describe institutional outbreaks Both in developing and industrialized countries Probably underestimated number of institutional outbreaks Basic institutional infection control sufficient to contain transmission in institutions

4 PatientsPlaceAssociation between tested forHIV status and any R HIV and DR Chum, 19961164TanzaniaNo association Kenyon, 1999240BotswanaNo association Churchyard, 20001913South AfricaNo association Warndorff, 2000836MalawiNo association Espinal, 2001463MulticenterNo association Mac-Arthur, 2001709MozambiqueAssociation with HS Weyer, not published762South Africa No association Association with MDR among retreatments Epidemiology in the general population

5 Generally no association between HIV status and DR, but: Majority of the studies in high HIV low MDR prevalence settings Lack of statistical power in some studies Methodologies difficult to compare In some studies association might be confounded by: –history of previous treatment –history of hospital stay Epidemiology in the general population

6 The case of Botswana From the Global Project on Anti-TB Drug Resistance

7 The case of Botswana From the Global Project on Anti-TB Drug Resistance

8 No of PatientsPotential Factors Dylewski, 19901HIV Small, 19911HIV and poor compliance Small, 19933HIV, drug / alcohol use, poor comp Godfrey-Faussett, 19931HIV, mutations population bacilli Nolan, 19953HIV, rpoB gene mutations Lutfey, 19966HIV, rpoB gene mutations, poor compliance March, 19973HIV, rpoB gene mutation (1), AZT fluconazole (1), Munsiff, 199729HIV, sputum smear (+), advanced immunosupp, and poor comp Vernon, 19994HIV, younger age, advanced immunosupp,extrap TB, and antifungal agents Jenny-Avital, 20021HIV, antiretroviral therapy Acquired Rifamycin resistance in previously susceptible HIV (+) patients

9 Acquired Rifamycin resistance in previously susceptible HIV (+) patients 2002: CDC suspended enrolment in Study 23 (single-arm trial of twice-weekly rifabutin based therapy for treatment of HIV-TB) because of the occurrence of five cases of acquired rifamycin resistance: Features: –very low CD4 cell count (<60 /mm3) at diagnosis –twice-weekly therapy in the continuation phase in developing and industrialized countries –relation appears to exist between the frequency of dosing and the risk of acquired resistance

10 Limited effect of highly intermittent regimens (continuation phase) on the mycobacterial replication which appear to be prolonged in advanced AIDS due host immunity Functional monotherapy during sterilisation of bacillary populations (shorter half-life of INH, malabsorption of INH - - ?) Inhibition of the p450 enzyme system by antifungal drugs Gene mutations Non-compliance with treatment Acquired Rifamycin Resistance Potential Mechanisms

11 What do we need to know Does HIV epidemic fuel MDR-TB epidemic? No evidence Dye C et al. Science. 2002;295(5562):2042-6 1.Reasons why DR should be found more often among HIV infected TB patients 2.Reasons why MDR-TB/HIV co-infected patients are less likely to transmit resistant strains

12 Reasons why DR prevalence could be higher among HIV infected TB patients 1.Immunosuppression and drug pressure affect fitness Ordway DJ et al. Infect Immun. 1995;63(2):741-3 2.PLWH have higher risk of MDR TB because of hospitalization/institutionalization, IDU 3.Acquisition of Rifamycin resistance in previously susceptible HIV (+) patients Vernon A et al. Lancet 1999; 353(9167): 1843-7

13 Reasons why MDR-TB/HIV co-infected patients are less likely to transmit resistant strains 1.HIV pos patients with TB are less likely than HIV neg patients with TB to transmit Mtb. Espinal MA et al. Lancet. 2000;22;355(9200):275-80 2.Higher mortality in MDR-TB/HIV patients (due to poorer treatment outcomes of MDR-TB)

14 What has to be done in order to fill the knowledge gap Conduct dual HIV and anti-TB drug resistance surveillance in 3 priority settings: 1.high HIV prevalence setting assess acquisition of RMP resistance during treatment 2.high MDR prevalence settings 3.high risk populations (hospitals, institutions, IDU) Variables to be studied at a minimum: –age –sex –history of TB treatment (therapy and prophylaxis) –history of hospitalization or imprisonment –infectiousness (smear positives vs. smear negatives) –intravenous drug use

15 What has to be done in order to fill the knowledge gap Modeling exercises Influence of HIV infection on MDR-TB not discussed by recent papers (Blower SM et al. Nat Med. 2004;10(10):1111-6 and Cohen T et al. Nat Med. 2004;10(10):1117-21) Need of good data!

16 What to do in the meantime Infection control 1.Encourage hospitals and institutions to monitor and document acquisition of (M)DR TB in TB/HIV co-infected patients 2.Advocate for implementation of measures of infection control in institutions

17 What to do in the meantime Population studies 1.Expand dual HIV and anti-TB drug resistance surveillance Ongoing projects: Botswana, Brazil, South Africa Determine new pilot sites: -Sub-Saharan countries ( Malawi) -Former Soviet Union countries (Baltic countries, Kyrgyzstan) 2.Studies in high risk populations (Baltic countries)


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