Isoniazid preventive therapy, HAART and tuberculosis risk in HIV-infected adults in South Africa: a prospective cohort

Abstract

Background The World Health Organization recommends isoniazid preventive therapy (IPT) for preventing tuberculosis in HIV-infected adults, although few countries have instituted this policy. Both IPT and highly active antiretroviral therapy (HAART) used separately result in reductions in tuberculosis risk. There is less information on the combined effect of IPT and HAART. We assessed the effect of IPT, HAART or both IPT and HAART on tuberculosis incidence in HIV-infected adults in South Africa. Methods Two clinical cohorts of HIV-infected patients were studied. Primary exposures were receipt of IPT and/or HAART and the primary outcome was incident tuberculosis. Crude incident rates and incident rate ratios were calculated and Cox proportional hazards models investigated associations with tuberculosis risk. Results Among 2778 HIV-infected patients followed for 4287 person-years, 267 incident tuberculosis cases were diagnosed [incidence rate ratio (IRR) = 6.2/100 person-years; 95% CI 5.5–7.0]. For person-time without IPT or HAART, the IRR was 7.1/100 person-years (95% CI 6.2–8.2); for person-time receiving HAART but without IPT, the IRR was 4.6/100 person-years (95% CI 3.4–6.2); for person-time after IPT but prior to HAART, the IRR was 5.2/100 person-years (95% CI 3.4–7.8); during follow-up in patients treated with HAART after receiving IPT the IRR was 1.1/100 person-years (95% CI 0.02–7.6). Compared to treatment-naive patients, HAART-only patients had a 64% decreased hazard for tuberculosis [adjusted hazard ratio (aHR) = 0.36; 95% CI 0.25–0.51], and patients receiving HAART after IPT had a 89% reduced hazard (aHR = 0.11; 95% CI 0.02–0.78). Conclusion Tuberculosis risk is significantly reduced by IPT in HAART-treated adults in a high-incidence operational setting in South Africa. IPT is an inexpensive and cost-effective strategy and our data strengthen calls for the implementation of IPT in conjunction with the roll-out of HAART.

Antiretroviral therapy for tuberculosis control in nine African countries

“…However, it is likely that the risk for TB continues to fall for up to 5 y after the start of ART (21), such that the present model may underestimate the impact of ART on TB. We have not included the impact of isoniazid preventive therapy (IPT) on the risk for developing TB in HIV-positive people, which may give a further reduction of about 50% (15,22). Because HIV-related TB has relatively little impact on the risk for TB in HIV-negative people, a good TB control program should be able to reduce the incidence of TB in HIV-negative people, even in the presence of a severe epidemic of HIV.…”

Tuberculosis in HIV-infected persons in British Columbia during the HAART era

“…[21][22][23][24][25][26][27][28][29] On a population level, however, the exact contribution of HAART to the reduction in TB incidence in HIV-infected population is less well characterized. 5,13 We could expect that contact structure may influence TB incidence at a population level, particularly if marginalized or populations at high risk for TB are targeted for HAART.…”

The HIV-associated tuberculosis epidemic—when will we act?

“…Studies from Brazil 81 and South Africa 82 suggest that sequential or concurrent use of ART and isoniazid preventive therapy could result in a synergistic decline in risk of active tuberculosis, and thus ART clinics are very suitable places in which to start implementation of the 3Is. WHO's advice for ART programmes to gradually phase out stavudine, 36 most probably in favour of tenofovir, will reduce the risk of additive peripheral neuropathy induced by isoniazid.…”