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Lancet Glob Health. 2017 Nov;5(11):e1080-e1089. doi: 10.1016/S2214-109X(17)30372-8.

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.

Author information

1
Inserm 1219, University of Bordeaux, Bordeaux, France; Programme PAC-CI, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Research Center, Abidjan, Côte d'Ivoire.
2
Inserm 1219, University of Bordeaux, Bordeaux, France; Programme PAC-CI, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Research Center, Abidjan, Côte d'Ivoire; Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire (CHU) de Treichville, Abidjan, Côte d'Ivoire.
3
Inserm 1219, University of Bordeaux, Bordeaux, France; Unité de Soins Ambulatoire et de Conseil (USAC), Treichville, Abidjan, Côte d'Ivoire.
4
Programme PAC-CI, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Research Center, Abidjan, Côte d'Ivoire; Centre de Diagnostic et de Recherches sur le SIDA (CeDReS), Centre Hospitalier Universitaire (CHU) de Treichville, Abidjan, Côte d'Ivoire.
5
Inserm 1219, University of Bordeaux, Bordeaux, France; Programme PAC-CI, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Research Center, Abidjan, Côte d'Ivoire; Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire (CHU) de Treichville, Abidjan, Côte d'Ivoire; Centre de Prise en Charge de Recherche et de Formation (CePReF), Yopougon, Abidjan, Côte d'Ivoire.
6
Programme PAC-CI, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Research Center, Abidjan, Côte d'Ivoire; Centre de Prise en Charge de Recherche et de Formation (CePReF), Yopougon, Abidjan, Côte d'Ivoire.
7
Inserm 1219, University of Bordeaux, Bordeaux, France; Programme PAC-CI, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Research Center, Abidjan, Côte d'Ivoire; Centre Médical de Suivi des Donneurs de Sang (CMSDS), Treichville, Abidjan, Côte d'Ivoire.
8
Centre de Prise en Charge de Recherche et de Formation (CePReF), Yopougon, Abidjan, Côte d'Ivoire.
9
Programme PAC-CI, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Research Center, Abidjan, Côte d'Ivoire; Centre de Diagnostic et de Recherches sur le SIDA (CeDReS), Centre Hospitalier Universitaire (CHU) de Treichville, Abidjan, Côte d'Ivoire; Centre Intégré de Recherches Biocliniques d'Abidjan (CIRBA), Treichville, Abidjan, Côte d'Ivoire.
10
Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire (CHU) de Treichville, Abidjan, Côte d'Ivoire.
11
Programme PAC-CI, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Research Center, Abidjan, Côte d'Ivoire; Centre Médical de Suivi des Donneurs de Sang (CMSDS), Treichville, Abidjan, Côte d'Ivoire.
12
Centre Médical de Suivi des Donneurs de Sang (CMSDS), Treichville, Abidjan, Côte d'Ivoire.
13
Hôpital Général d'Abobo Nord, Abobo, Abidjan, Côte d'Ivoire.
14
Centre Intégré de Recherches Biocliniques d'Abidjan (CIRBA), Treichville, Abidjan, Côte d'Ivoire.
15
Unité de Soins Ambulatoire et de Conseil (USAC), Treichville, Abidjan, Côte d'Ivoire.
16
Formation Sanitaire Urbaine Communautaire (FSU Com) d'Anonkoua Kouté, Abobo, Abidjan, Côte d'Ivoire.
17
Hôpital El Rapha, Abobo, Abidjan, Côte d'Ivoire.
18
Centre La Pierre Angulaire, Treichville, Abidjan, Côte d'Ivoire.
19
Laboratoire de virologie, CHU Necker, Paris, France.
20
Programme National de Lutte contre le SIDA, Ministère de la Sante et de l'Hygiène Publique, Abidjan, Côte d'Ivoire.
21
Service de Pneumologie, Centre Hospitalier Universitaire (CHU) de Treichville, Abidjan, Côte d'Ivoire.
22
Programme PAC-CI, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Research Center, Abidjan, Côte d'Ivoire.
23
Programme PAC-CI, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Research Center, Abidjan, Côte d'Ivoire; Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire (CHU) de Treichville, Abidjan, Côte d'Ivoire.
24
Programme PAC-CI, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Research Center, Abidjan, Côte d'Ivoire; Service de Gastro-entéro-hépatologie, CHU de Yopougon, Abidjan, Côte d'Ivoire.
25
Inserm 1219, University of Bordeaux, Bordeaux, France.
26
Inserm 1219, University of Bordeaux, Bordeaux, France; Programme PAC-CI, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) Research Center, Abidjan, Côte d'Ivoire. Electronic address: xavier.anglaret@u-bordeaux.fr.

Abstract

BACKGROUND:

Temprano 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.

METHODS:

For 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.

FINDINGS:

Between 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.

INTERPRETATION:

In 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.

FUNDING:

National Research Agency on AIDS and Viral Hepatitis (ANRS).

PMID:
29025631
DOI:
10.1016/S2214-109X(17)30372-8
[Indexed for MEDLINE]
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