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Isoniazid preventive therapy in a time of HIV, TB, and MDR

Isoniazid preventive therapy in a time of HIV, TB, and MDR. Why do TB and HIV programs and the HIV community itself ignore IPT?. WHO Recommended Policy on Collaborative TB/HIV Activities

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Isoniazid preventive therapy in a time of HIV, TB, and MDR

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  1. Isoniazid preventive therapy in a time of HIV, TB, and MDR

  2. Why do TB and HIV programs and the HIV community itself ignore IPT? WHO Recommended Policy on Collaborative TB/HIV Activities • HIV/AIDS programmes should provide isoniazid preventive therapy as part of the package of care for people living with HIV/AIDS when active TB is safely excluded. • Countries have been ignoring WHO’s advice for IPT for at least a decade. Paper policies do not lead to actual program implementation in practice. 2. Information about isoniazid preventive therapy should be made available to all people living with HIV/AIDS. • TB programs provide inaccurate information about IPT and deride its effectiveness while HIV programs ignore IPT. • Community activist groups and PWA groups have not done enough to educate their peers about IPT and create demand.

  3. How strong is the evidence? Q: How strong is the evidence that IPT works? A: Overwhelming.

  4. Effect of IPT on TB in PPD+ve PLWHA:meta-analysis of clinical trials Relative risk, 95% CI 1.0 Placebo Overall TST+ TST- Woldehanna 2004, Cochrane review

  5. How much IPT is being done? Q: How much IPT is being done as part of worldwide scale-up of HIV prevention, care, and treatment services? A: Pathetically little.Only 27,056 in 2006 – equivalent to less than 0.1% of the estimated 33 million people estimated to be infected with HIV globally… While 84 countries reported the existence of an IPT policy, only 25 reported any provision… Numbers on IPT are dominated by Botswana, which accounted for 70% of the total number… globally in 2006.” -- WHO TB report 2008

  6. Excuses for not implementing IPT • IPT worsens drug resistance. • It’s not needed if you’re on ART. • It’s too toxic. • It’s too hard to rule out active TB. • IPT is too complicated and costly. • IPT adherence is poor.

  7. Objection 1: Resistance • Claim: IPT promotes drug resistant disease and renders first-line therapy less effective when active TB occurs. • Fact: IPT does not promote drug resistant disease; it reduces TB incidence by 40-60%; and when active TB occurs among those given IPT, standard four-drug first-line therapy works.

  8. Does IPT promote INH resistant TB? • IPT effective even if relatively high prevalence of INH resistance – eg 17% in Haiti in 1990s (Chaisson ARRCCM 1996;154:1034) • If TB is latent, few organisms, dividing slowly, thus low risk of selection of DR-TB • Standard quadruple therapy is effective for INH-r TB (Nolan IJTLD 2002;6:952)

  9. Does IPT promote isoniazid resistance? Balcells Emerg Infect Dis 2006;12:744

  10. Does IPT promote isoniazid resistance? • Combined average of previous 13 studies analyzed shows risk of increased resistance, if any, is small: • summary RR = 1.45 (95% CI 0.85, 2.47) • most resistance arises from suboptimal treatment of active disease, so preventing active disease will reduce resistance • need for surveillance for resistance • need for implementation research

  11. Objection 2: IPT not necessary because ART is good enough • Claim: IPT is not necessary because ART alone is good enough in reducing TB incidence. • Fact: IPT and ART are synergistic in reducing TB incidence among people with HIV taking both.

  12. Risk factors for TB on ART: UK * time-updated Grant CROI 2007 abs 846

  13. Effect of ART on TB (South Africa) Lawn AIDS 2005;19:2109

  14. Effect of ART + IPT in Brazil Retrospective review of TB incidence in 11,026 HIV+ at 29 public clinics in RJ between 1 Sep 03-1 Sep 05. TB reduction (%)* No ART, no IPT 4.01 cases/100 person years 0 ART, no IPT 1.90 cases/100 py 52.5% IPT, no ART 1.27 cases/100 py 68.3% ART + IPT 0.80 cases/100 py 80.0% * Compared with no ART/no IPT. After adjusting for age, previous TB, and baseline CD4 count the overall reduction seen with ART+IPT was 76% vs. no intervention. -- Golub JE, Saraceni V, Cavalcante SC, et al. The impact of ART and isoniazid preventive therapy on TB incidence in HIV-infected patients in Rio de Janeiro, Brazil. AIDS. 2007 Jul 11;21(11):1441-8.

  15. Objection 3: Toxicity Claim: IPT is too toxic for people with HIV (on or not on ART) and has additive toxicity with ART> Fact: IPT is far less toxic than HRZE and has far fewer interactions with ART than R; IPT toxicity is rare and can be managed.

  16. IPT: hepatotoxicity rare Uganda RCT • 7/931 AST>135u; total 3 stopped with any adverse event (Whalen NEJM 1997;337:801) South Africa, routine, pre ART • 1/777 stopped INH with asymptomatic raised AST ref?AMA 2005;293:2719) South Africa, ART cohort • IPT not associated with higher risk of hepatotoxicity (Hoffmann AIDS 2007;21:1301)

  17. Objection 4: It’s too hard to rule out active TB Claim:It’s too hard to rule out active TB among HIV+ persons. Fact: If countries use intensified case finding and implement the new WHO diagnostic algorithm for smear-negative and extrapulmonary TB active TB case detection will increase.

  18. Objection 5: IPT is too costly & complicated “IPT is an effective intervention on an individual basis if patients can complete the 6-9 months regimen and if there is a system to support them… Screening, sensitizing the HIV community and ensuring that people living with HIV can complete the entire duration of treatment is resource intensive…” -- Saidi Egwaga, NTLP Program Manager, Tanzania

  19. IPT is cheaper and easier than treating active TB disease! Claim: IPT is too costly and complicated. Fact: It’s a lot easier to take one very effective and non-toxic drug for six to nine months to prevent potentially fatal TB than it is to take six months of TB treatment when you’ve got a high risk of early mortality (up to 33%) even if you’re on ART. In this case prevention really is cheaper than treatment.

  20. Objection 6: IPT adherence is poor Claim: IPT adherence is poor. Fact: Lack of clarity about who is responsible for IPT means that no one is responsible for providing IPT or for promoting adherence. Fact: People with HIV have amazingly high adherence to ART; why don’t HIV treatment programs use HIV adherence training and support methods to increase uptake and adherence to IPT.

  21. Retention on IPT: Zambia number of patients 23% months on IPT Ayles Int Conf on AIDS, Durban 2000 [Abstract ThPeB5212]

  22. What is needed? • HIV programs must take responsibility. • HIV community/PHA group must take responsibility. • Operational research should be done but not as an excuse to delay implementation. • Failure to provide IPT is a violation of human rights and will worsen the DR-TB epidemic among people with HIV.

  23. Issues to consider • Duration IPT; shorter 2 drug PT regimens? • Better HIV cohort reporting & recording integrating IPT and CTX. • Lack of standard guidelines for follow-up of healthy (pre-ART) HIV patients in RLS. • Need to record active TB incidence in districts with + without IPT. • Need to measure impact if any on DR-TB. • Evaluate different adherence approaches.

  24. Acknowledgments • Aurum • CREATE • JHU • LSHTM • THRio • WHO HIV + STB Departments • Bill & Melinda Gates Foundation • TB, HIV, and TB/HIV activist colleagues

  25. TAC TB march, 2007

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