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

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...

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Main Authors: Anani Badje, MPH (Author), Raoul Moh, PhD (Author), Delphine Gabillard, MSc (Author), Calixte Guéhi, PhD (Author), Mathieu Kabran, PharmD (Author), Jean-Baptiste Ntakpé, MPH (Author), Jérôme Le Carrou, PhD (Author), Gérard M Kouame, MPH (Author), Eric Ouattara, PhD (Author), Eugène Messou, PhD (Author), Amani Anzian, MD (Author), Albert Minga, PhD (Author), Joachim Gnokoro, MD (Author), Patrice Gouesse, MD (Author), Arlette Emieme, PharmD (Author), Thomas-d'Aquin Toni, PhD (Author), Cyprien Rabe, MD (Author), Baba Sidibé, MD (Author), Gustave Nzunetu, MD (Author), Lambert Dohoun, MD (Author), Abo Yao, MPH (Author), Synali Kamagate, MD (Author), Solange Amon, MD (Author), Amadou-Barenson Kouame, MD (Author), Aboli Koua, MD (Author), Emmanuel Kouamé, MD (Author), Marcelle Daligou, MD (Author), Denise Hawerlander, MD (Author), Simplice Ackoundzé, MD (Author), Serge Koule, MD (Author), Jonas Séri, MD (Author), Alex Ani, MD (Author), Fassery Dembélé, MD (Author), Fatoumata Koné, MD (Author), Mykayila Oyebi, MD (Author), Nathalie Mbakop, MD (Author), Oyewole Makaila, MD (Author), Carolle Babatunde, MD (Author), Nathaniel Babatunde, MD (Author), Gisèle Bleoué, MD (Author), Mireille Tchoutedjem, MD (Author), Alain-Claude Kouadio, MD (Author), Ghislaine Sena, MD (Author), Sahinou-Yediga Yededji, MD (Author), Sophie Karcher, MSc (Author), Prof Christine Rouzioux, PhD (Author), Abo Kouame, MD (Author), Rodrigue Assi, MD (Author), Alima Bakayoko, MD (Author), Prof Serge K Domoua, PhD (Author), Nina Deschamps, MPH (Author), Prof Kakou Aka, MD (Author), Prof Thérèse N'Dri-Yoman, MD (Author), Prof Roger Salamon, PhD (Author), Valérie Journot, PhD (Author), Prof Hughes Ahibo, PhD (Author), Prof Timothée Ouassa, PhD (Author), Prof Hervé Menan, PhD (Author), Prof André Inwoley, PhD (Author), Christine Danel, PhD (Author), Prof Serge P Eholié, PhD (Author), Dr Xavier Anglaret, PhD (Author), Anani Badje (Author), Raoul Moh (Author), Delphine Gabillard (Author), Calixte Guéhi (Author), Mathieu Kabran (Author), Jean-Baptiste Ntakpé (Author), Jérôme Le Carrou (Author), Gérard-Menan Kouame (Author), Eric Ouattara (Author), Eugène Messou (Author), Amani Anzian (Author), Albert Minga (Author), Joachim Gnokoro (Author), Patrice Gouesse (Author), Arlette Emieme (Author), Thomas-d'Aquin Toni (Author), Cyprien Rabe (Author), Baba Sidibé (Author), Gustave Nzunetu (Author), Lambert Dohoun (Author), Yao Abo (Author), Synali Kamagate (Author), Solange Amon (Author), Amadou-Barenson Kouame (Author), Aboli Koua (Author), Emmanuel Kouamé (Author), Marcelle Daligou (Author), Denise Hawerlander (Author), Simplice Ackoundzé (Author), Serge Koule (Author), Jonas Séri (Author), Alex Ani (Author), Fassery Dembélé (Author), Fatoumata Koné (Author), Mykayila Oyebi (Author), Nathalie Mbakop (Author), Oyewole Makaila (Author), Carolle Babatunde (Author), Nathaniel Babatunde (Author), Gisèle Bleoué (Author), Mireille Tchoutedjem (Author), Alain-Claude Kouadio (Author), Ghislaine Sena (Author), Sahinou-Yediga Yededji (Author), Sophie Karcher (Author), Christine Rouzioux (Author), Abo Kouame (Author), Rodrigue Assi (Author), Alima Bakayoko (Author), Serge-K. Domoua (Author), Nina Deschamps (Author), Kakou Aka (Author), Thérèse N'Dri-Yoman (Author), Roger Salamon (Author), Valérie Journot (Author), Hughes Ahibo (Author), Timothée Ouassa (Author), Hervé Ménan (Author), André Inwoley (Author), Ben-Ahoussi Ndja (Author), Blandine Adou (Author), Constance Kanga (Author), Eba Aoussi (Author), Emmanuel Bissagnene (Author), Olivier Ba-Gomis (Author), Yves-Alain Zike (Author), Claude Akakpo (Author), Madeleine Sassan-Morokro (Author), Max Mobio (Author), Bamba Doféré (Author), Koman Mesmin (Author), Alain Attia (Author), Alassane Mahassadi (Author), Apollinaire Horo (Author), Armel Oussou (Author), Marie-Laure Chaix (Author), Gilles Peytavin (Author), Mariatou Koné (Author), Kouamé N'Guessan (Author), Raïmi Fassassi (Author), Serge Niangoran (Author), Annabel Desgrées- (Author), France Lert (Author), Rosemary Dray Spira (Author), Kevin Jean (Author), Romuald Konan (Author), Franck Bohoussou (Author), Cyril Yao-Yapi (Author), Larissa N'guessan-Koffi (Author), Bertine Siloué (Author), Adoulaye Cissé (Author), Adrienne Aboua (Author), Sylvie Konan (Author), Antoine Kouamé (Author), Celestin N'Chot (Author), Elvis Amani (Author), Gwenaëlle Clouet (Author), Bruno Debono (Author), Geneviève Chêne (Author), Mireille Dosso (Author), Pierre-Marie Girard (Author), Vincent Jarlier (Author), Jean-Marie Masumbuko (Author), Christian Perronne (Author), Papa-Salif Sow (Author), Christine Danel (Author), Serge-Paul Eholié (Author), Xavier Anglaret (Author)
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Published: Elsevier, 2017-11-01T00:00:00Z.
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100 1 0 |a Anani Badje, MPH  |e author 
700 1 0 |a Raoul Moh, PhD  |e author 
700 1 0 |a Delphine Gabillard, MSc  |e author 
700 1 0 |a Calixte Guéhi, PhD  |e author 
700 1 0 |a Mathieu Kabran, PharmD  |e author 
700 1 0 |a Jean-Baptiste Ntakpé, MPH  |e author 
700 1 0 |a Jérôme Le Carrou, PhD  |e author 
700 1 0 |a Gérard M Kouame, MPH  |e author 
700 1 0 |a Eric Ouattara, PhD  |e author 
700 1 0 |a Eugène Messou, PhD  |e author 
700 1 0 |a Amani Anzian, MD  |e author 
700 1 0 |a Albert Minga, PhD  |e author 
700 1 0 |a Joachim Gnokoro, MD  |e author 
700 1 0 |a Patrice Gouesse, MD  |e author 
700 1 0 |a Arlette Emieme, PharmD  |e author 
700 1 0 |a Thomas-d'Aquin Toni, PhD  |e author 
700 1 0 |a Cyprien Rabe, MD  |e author 
700 1 0 |a Baba Sidibé, MD  |e author 
700 1 0 |a Gustave Nzunetu, MD  |e author 
700 1 0 |a Lambert Dohoun, MD  |e author 
700 1 0 |a Abo Yao, MPH  |e author 
700 1 0 |a Synali Kamagate, MD  |e author 
700 1 0 |a Solange Amon, MD  |e author 
700 1 0 |a Amadou-Barenson Kouame, MD  |e author 
700 1 0 |a Aboli Koua, MD  |e author 
700 1 0 |a Emmanuel Kouamé, MD  |e author 
700 1 0 |a Marcelle Daligou, MD  |e author 
700 1 0 |a Denise Hawerlander, MD  |e author 
700 1 0 |a Simplice Ackoundzé, MD  |e author 
700 1 0 |a Serge Koule, MD  |e author 
700 1 0 |a Jonas Séri, MD  |e author 
700 1 0 |a Alex Ani, MD  |e author 
700 1 0 |a Fassery Dembélé, MD  |e author 
700 1 0 |a Fatoumata Koné, MD  |e author 
700 1 0 |a Mykayila Oyebi, MD  |e author 
700 1 0 |a Nathalie Mbakop, MD  |e author 
700 1 0 |a Oyewole Makaila, MD  |e author 
700 1 0 |a Carolle Babatunde, MD  |e author 
700 1 0 |a Nathaniel Babatunde, MD  |e author 
700 1 0 |a Gisèle Bleoué, MD  |e author 
700 1 0 |a Mireille Tchoutedjem, MD  |e author 
700 1 0 |a Alain-Claude Kouadio, MD  |e author 
700 1 0 |a Ghislaine Sena, MD  |e author 
700 1 0 |a Sahinou-Yediga Yededji, MD  |e author 
700 1 0 |a Sophie Karcher, MSc  |e author 
700 1 0 |a Prof Christine Rouzioux, PhD  |e author 
700 1 0 |a Abo Kouame, MD  |e author 
700 1 0 |a Rodrigue Assi, MD  |e author 
700 1 0 |a Alima Bakayoko, MD  |e author 
700 1 0 |a Prof Serge K Domoua, PhD  |e author 
700 1 0 |a Nina Deschamps, MPH  |e author 
700 1 0 |a Prof Kakou Aka, MD  |e author 
700 1 0 |a Prof Thérèse N'Dri-Yoman, MD  |e author 
700 1 0 |a Prof Roger Salamon, PhD  |e author 
700 1 0 |a Valérie Journot, PhD  |e author 
700 1 0 |a Prof Hughes Ahibo, PhD  |e author 
700 1 0 |a Prof Timothée Ouassa, PhD  |e author 
700 1 0 |a Prof Hervé Menan, PhD  |e author 
700 1 0 |a Prof André Inwoley, PhD  |e author 
700 1 0 |a Christine Danel, PhD  |e author 
700 1 0 |a Prof Serge P Eholié, PhD  |e author 
700 1 0 |a Dr Xavier Anglaret, PhD  |e author 
700 1 0 |a Anani Badje  |e author 
700 1 0 |a Raoul Moh  |e author 
700 1 0 |a Delphine Gabillard  |e author 
700 1 0 |a Calixte Guéhi  |e author 
700 1 0 |a Mathieu Kabran  |e author 
700 1 0 |a Jean-Baptiste Ntakpé  |e author 
700 1 0 |a Jérôme Le Carrou  |e author 
700 1 0 |a Gérard-Menan Kouame  |e author 
700 1 0 |a Eric Ouattara  |e author 
700 1 0 |a Eugène Messou  |e author 
700 1 0 |a Amani Anzian  |e author 
700 1 0 |a Albert Minga  |e author 
700 1 0 |a Joachim Gnokoro  |e author 
700 1 0 |a Patrice Gouesse  |e author 
700 1 0 |a Arlette Emieme  |e author 
700 1 0 |a Thomas-d'Aquin Toni  |e author 
700 1 0 |a Cyprien Rabe  |e author 
700 1 0 |a Baba Sidibé  |e author 
700 1 0 |a Gustave Nzunetu  |e author 
700 1 0 |a Lambert Dohoun  |e author 
700 1 0 |a Yao Abo  |e author 
700 1 0 |a Synali Kamagate  |e author 
700 1 0 |a Solange Amon  |e author 
700 1 0 |a Amadou-Barenson Kouame  |e author 
700 1 0 |a Aboli Koua  |e author 
700 1 0 |a Emmanuel Kouamé  |e author 
700 1 0 |a Marcelle Daligou  |e author 
700 1 0 |a Denise Hawerlander  |e author 
700 1 0 |a Simplice Ackoundzé  |e author 
700 1 0 |a Serge Koule  |e author 
700 1 0 |a Jonas Séri  |e author 
700 1 0 |a Alex Ani  |e author 
700 1 0 |a Fassery Dembélé  |e author 
700 1 0 |a Fatoumata Koné  |e author 
700 1 0 |a Mykayila Oyebi  |e author 
700 1 0 |a Nathalie Mbakop  |e author 
700 1 0 |a Oyewole Makaila  |e author 
700 1 0 |a Carolle Babatunde  |e author 
700 1 0 |a Nathaniel Babatunde  |e author 
700 1 0 |a Gisèle Bleoué  |e author 
700 1 0 |a Mireille Tchoutedjem  |e author 
700 1 0 |a Alain-Claude Kouadio  |e author 
700 1 0 |a Ghislaine Sena  |e author 
700 1 0 |a Sahinou-Yediga Yededji  |e author 
700 1 0 |a Sophie Karcher  |e author 
700 1 0 |a Christine Rouzioux  |e author 
700 1 0 |a Abo Kouame  |e author 
700 1 0 |a Rodrigue Assi  |e author 
700 1 0 |a Alima Bakayoko  |e author 
700 1 0 |a Serge-K. Domoua  |e author 
700 1 0 |a Nina Deschamps  |e author 
700 1 0 |a Kakou Aka  |e author 
700 1 0 |a Thérèse N'Dri-Yoman  |e author 
700 1 0 |a Roger Salamon  |e author 
700 1 0 |a Valérie Journot  |e author 
700 1 0 |a Hughes Ahibo  |e author 
700 1 0 |a Timothée Ouassa  |e author 
700 1 0 |a Hervé Ménan  |e author 
700 1 0 |a André Inwoley  |e author 
700 1 0 |a Ben-Ahoussi Ndja  |e author 
700 1 0 |a Blandine Adou  |e author 
700 1 0 |a Constance Kanga  |e author 
700 1 0 |a Eba Aoussi  |e author 
700 1 0 |a Emmanuel Bissagnene  |e author 
700 1 0 |a Olivier Ba-Gomis  |e author 
700 1 0 |a Yves-Alain Zike  |e author 
700 1 0 |a Claude Akakpo  |e author 
700 1 0 |a Madeleine Sassan-Morokro  |e author 
700 1 0 |a Max Mobio  |e author 
700 1 0 |a Bamba Doféré  |e author 
700 1 0 |a Koman Mesmin  |e author 
700 1 0 |a Alain Attia  |e author 
700 1 0 |a Alassane Mahassadi  |e author 
700 1 0 |a Apollinaire Horo  |e author 
700 1 0 |a Armel Oussou  |e author 
700 1 0 |a Marie-Laure Chaix  |e author 
700 1 0 |a Gilles Peytavin  |e author 
700 1 0 |a Mariatou Koné  |e author 
700 1 0 |a Kouamé N'Guessan  |e author 
700 1 0 |a Raïmi Fassassi  |e author 
700 1 0 |a Serge Niangoran  |e author 
700 1 0 |a Annabel Desgrées-  |e author 
700 1 0 |a France Lert  |e author 
700 1 0 |a Rosemary Dray Spira  |e author 
700 1 0 |a Kevin Jean  |e author 
700 1 0 |a Romuald Konan  |e author 
700 1 0 |a Franck Bohoussou  |e author 
700 1 0 |a Cyril Yao-Yapi  |e author 
700 1 0 |a Larissa N'guessan-Koffi  |e author 
700 1 0 |a Bertine Siloué  |e author 
700 1 0 |a Adoulaye Cissé  |e author 
700 1 0 |a Adrienne Aboua  |e author 
700 1 0 |a Sylvie Konan  |e author 
700 1 0 |a Antoine Kouamé  |e author 
700 1 0 |a Celestin N'Chot  |e author 
700 1 0 |a Elvis Amani  |e author 
700 1 0 |a Gwenaëlle Clouet  |e author 
700 1 0 |a Bruno Debono  |e author 
700 1 0 |a Geneviève Chêne  |e author 
700 1 0 |a Mireille Dosso  |e author 
700 1 0 |a Pierre-Marie Girard  |e author 
700 1 0 |a Vincent Jarlier  |e author 
700 1 0 |a Jean-Marie Masumbuko  |e author 
700 1 0 |a Christian Perronne  |e author 
700 1 0 |a Papa-Salif Sow  |e author 
700 1 0 |a Christine Danel  |e author 
700 1 0 |a Serge-Paul Eholié  |e author 
700 1 0 |a Xavier Anglaret  |e author 
245 0 0 |a 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 
260 |b Elsevier,   |c 2017-11-01T00:00:00Z. 
500 |a 2214-109X 
500 |a 10.1016/S2214-109X(17)30372-8 
520 |a 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). 
546 |a EN 
690 |a Public aspects of medicine 
690 |a RA1-1270 
655 7 |a article  |2 local 
786 0 |n The Lancet Global Health, Vol 5, Iss 11, Pp e1080-e1089 (2017) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S2214109X17303728 
787 0 |n https://doaj.org/toc/2214-109X 
856 4 1 |u https://doaj.org/article/c5d7eb49263d4e08a3d2d62ed936400d  |z Connect to this object online.