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

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.