THLBB03 - Oral Abstract
Randomized controlled trial of isoniazid preventive therapy in HIV-infected persons on antiretroviral therapy
Presented by Molebogeng Rangaka (South Africa).
M.X. Rangaka1,2,3, A. Boulle1, R.J. Wilkinson2,4, G. van Cutsem1,5, E. Goemaere5, R. Goliath2, R. Titus2, S. Mathee6, G. Maartens7
1University 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,
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.
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