Abstract

THLBB03 - Oral Abstract Session

Randomized controlled trial of isoniazid preventive therapy in HIV-infected persons on antiretroviral therapy

Presented by Molebogeng Rangaka (South Africa).

M.X. Rangaka^1,2,3, A. Boulle¹, R.J. Wilkinson^2,4, G. van Cutsem^1,5, E. Goemaere⁵, R. Goliath², R. Titus², S. Mathee⁶, G. Maartens<sup>7

1</sup>University of Cape Town, School of Public Health, Centre for Infectious Disease Epidemiology and Research, Cape Town, South Africa, ²University of Cape Town, Institute of Infectious Diseases and Molecular Medicine, Clinical Infectious Diseases Research Initiative, Cape Town, South Africa, ³London School of Hygiene and Tropical Medicine, (LSHTM), London, United Kingdom, ⁴Imperial College London, Division of Medicine, London, United Kingdom, ⁵Medecins Sans Frontieres South Africa, Khayelitsha ART Programme, Khayelitsha, Cape Town, South Africa, ⁶Provincial Government of the Western Cape, Cape Town, South Africa, ⁷University of Cape Town, Department of Medicine, Pharmacology Unit, Cape Town, South Africa

Background: Antiretroviral therapy (ART) reduces the risk of tuberculosis, but the incidence still exceeds that in HIV-uninfected people. Retrospective cohort studies suggest an additive benefit of isoniazid preventive therapy (IPT) in patients on ART, but there are no controlled data on the efficacy and safety of IPT for patients on ART.
Methods: Using a pragmatic randomized double-blind placebo-controlled study design, we evaluated the efficacy of IPT among HIV-infected participants established on ART or newly starting ART in Khayelitsha, South Africa. Participants were randomized to daily isoniazid or matching placebo for twelve months, and followed for up to four years. Tuberculosis was excluded at screening by sputum culture. Development of incident tuberculosis was the primary endpoint. Secondary endpoints included toxicities and deaths.
Results: 1,329 participants contributed 3227 person-years (PY) of follow-up in the modified intention to treat analysis; 662 on placebo and 667 on IPT, with comparable CD4+ count and proportion starting ART. Overall there were 95 incident tuberculosis cases: 3.6 (95% CI 2.8-4.7) versus 2.3 (95% CI 1.6-3.1) per 100 PY in the placebo and IPT arms respectively (HR 0.63, 95% CI 0.41-0.94, p=0.026). Study drug was discontinued due to pre-specified toxicity in 2.5% in the placebo arm and 4.1% in the IPT arm (logrank p=0.13). The number of deaths was similar between arms (3.0% and 2.1 respectively, logrank p=0.29).
Conclusions: Under field conditions, twelve months of IPT reduced the incidence of TB without causing excess harm in HIV-infected individuals established on ART or newly starting ART. It is feasible to implement IPT in busy ART clinics in settings with high HIV/TB co-morbidity.