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Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial

2017; Elsevier BV; Volume: 5; Issue: 11 Linguagem: Inglês

10.1016/s2214-109x(17)30372-8

2572-116X

Anani Badjé, Raoul Moh, Delphine Gabillard, Calixte Guéhi, Mathieu Kabran, Kévin Jean, Jérôme Le Carrou, Gérard Menan Kouamé, Éric Ouattara, Éric Ouattara, Amani Anzian, Amani Anzian, Albert Minga, Joachim Gnokoro, Arlette Emième, Arlette Emième, Cyprien Rabe, Baba Sidibé, Baba Sidibé, Gustave Nzunetu, Yao Abo, Yao Abo, Solange Amon, Amadou-Barenson Kouame, Aboli Koua, Emmanuel Kouamé, Marcelle Daligou, Denise Hawerlander, Denise Hawerlander, Serge Koule, Serge Koule, Alex Ani, Fassery Dembélé, Fassery Dembele, Fatoumata Koné, Nathalie Mbakop, Oyewole Makaila, Geneviève Chêne, Mireille Dosso, Pierre‐Marie Girard, Vincent Jarlier, Jean-Marie Masumbuko, Christian Perronne, Sahinou-Yediga Yededji, Christine Danel, Serge‐Paul Eholié, Xavier Anglaret, R. Assi, A.S. Bakayoko, Serge K Domoua, Nina Deschamps, Kakou Aka, Thérèse N’Dri-Yoman, Roger Salamon, Valérie Journot, Hughes Ahibo, Timothée Ouassa, Hervé Ménan, André Inwoley, Christine Danel, Serge Eholié, Xavier Anglaret, Anani Badjé, Raoul Moh, Delphine Gabillard, Calixte Guéhi, Mathieu Kabran, Kévin Jean, Jérôme Le Carrou, Gérard Menan Kouamé, Éric Ouattara, Éric Ouattara, Amani Anzian, Amani Anzian, Albert Minga, Joachim Gnokoro, Arlette Emième, Arlette Emième, Cyprien Rabe, Cyprien Rabe, Baba Sidibé, Gustave Nzunetu, Yao Abo, Yao Abo, Solange Amon, Amadou-Barenson Kouame, Aboli Koua, Emmanuel Kouamé, Marcelle Daligou, Denise Hawerlander, Denise Hawerlander, Serge Koule, Serge Koule, Alex Ani, Fassery Dembélé, Fassery Dembele, Fatoumata Koné, Nathalie Mbakop, Oyewole Makaila, Geneviève Chêne, Mireille Dosso, Pierre‐Marie Girard, Vincent Jarlier, Jean-Marie Masumbuko, Christian Perronne, Sahinou-Yediga Yededji, Christine Danel, Serge‐Paul Eholié, Xavier Anglaret, R. Assi, A.S. Bakayoko, Serge K Domoua, Nina Deschamps, Kakou Aka, Thérèse N’Dri-Yoman, Roger Salamon, Valérie Journot, Hughes Ahibo, Timothée Ouassa, Hervé Ménan, André Inwoley, Ben-Ahoussi Ndja, Blandine Adou, Constance Kanga, E. Aoussi, E. Bissagnéné, Olivier Ba-Gomis, Yves-Alain Zike, Claude Akakpo, Madeleine Sassan‐Morokro, M P Mobio, Bamba Doféré, Koman Mesmin, Alain Attia, Alassan Kouamé Mahassadi, Apollinaire Horo, A Oussou, Marie‐Laure Chaix, Gilles Peytavin, Mariatou Koné, Koffi N’Guessan, Raïmi Fassassi, Serge Niangoran, Annabel Desgrées du Loû, France Lert, Rosemary Dray‐Spira, Kévin Jean, Romuald Konan, Franck Bohoussou, Cyril Yao-Yapi, Larissa N'guessan-Koffi, Bertine Siloué, Adoulaye Cissé, Adrienne Aboua, Sylvie Konan, Antoine Kouamé, Célestin N’Chot, Elvis Amani, Gwenaëlle Clouet, Bertrand Debono, Geneviève Chêne, Mireille Dosso, Pierre‐Marie Girard, Vincent Jarlier, Jean-Marie Masumbuko, Christian Perronne, P.S. Sow, Christine Danel, Serge‐Paul Eholié, Xavier Anglaret,

HIV/AIDS drug development and treatment

BackgroundTemprano ANRS 12136 was a factorial 2 × 2 trial that assessed the benefits of early antiretroviral therapy (ART; ie, in patients who had not reached the CD4 cell count threshold used to recommend starting ART, as per the WHO guidelines that were the standard during the study period) and 6-month isoniazid preventive therapy (IPT) in HIV-infected adults in Côte d'Ivoire. Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here, we present the efficacy of IPT in reducing mortality from the long-term follow-up of Temprano.MethodsFor Temprano, participants were randomly assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early ART plus IPT). Participants who completed the trial follow-up were invited to participate in a post-trial phase. The primary post-trial phase endpoint was death, as analysed by the intention-to-treat principle. We used Cox proportional models to compare all-cause mortality between the IPT and no IPT strategies from inclusion in Temprano to the end of the follow-up period.FindingsBetween March 18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per μL) were followed up for 9404 patient-years (Temprano 4757; post-trial phase 4647). The median follow-up time was 4·9 years (IQR 3·3–5·8). 86 deaths were recorded (Temprano 47 deaths; post-trial phase 39 deaths), of which 34 were in patients randomly assigned IPT (6-year probability 4·1%, 95% CI 2·9–5·7) and 52 were in those randomly assigned no IPT (6·9%, 5·1–9·2). The hazard ratio of death in patients who had IPT compared with those who did not have IPT was 0·63 (95% CI, 0·41 to 0·97) after adjusting for the ART strategy (early vs deferred), and 0·61 (0·39–0·94) after adjustment for the ART strategy, baseline CD4 cell count, and other key characteristics. There was no evidence for statistical interaction between IPT and ART (pinteraction=0·77) or between IPT and time (pinteraction=0·94) on mortality.InterpretationIn Côte d'Ivoire, where the incidence of tuberculosis was last reported as 159 per 100 000 people, 6 months of IPT has a durable protective effect in reducing mortality in HIV-infected people, even in people with high CD4 cell counts and who have started ART.FundingNational Research Agency on AIDS and Viral Hepatitis (ANRS).