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A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

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Title: A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa
Authors: TEMPRANO ANRS 12136 Study Group
Danel, C
Moh, R
Gabillard, D
Badje, A
Le Carrou, J
Ouassa, T
Ouattara, E
Anzian, A
Ntakpé, JB
Minga, A
Kouame, GM
Bouhoussou, F
Emieme, A
Kouamé, A
Inwoley, A
Toni, TD
Ahiboh, H
Kabran, M
Rabe, C
Sidibé, B
Nzunetu, G
Konan, R
Gnokoro, J
Gouesse, P
Messou, E
Dohoun, L
Kamagate, S
Yao, A
Amon, S
Kouame, AB
Koua, A
Kouamé, E
Ndri, Y
Ba-Gomis, O
Daligou, M
Ackoundzé, S
Hawerlander, D
Ani, A
Dembélé, F
Koné, F
Guéhi, C
Kanga, C
Koule, S
Séri, J
Oyebi, M
Mbakop, N
Makaila, O
Babatunde, C
Babatounde, N
Bleoué, G
Tchoutedjem, M
Kouadio, AC
Sena, G
Yededji, SY
Assi, R
Bakayoko, A
Mahassadi, A
Attia, A
Oussou, A
Mobio, M
Bamba, D
Koman, M
Horo, A
Deschamps, N
Chenal, H
Sassan-Morokro, M
Konate, S
Aka, K
Aoussi, E
Journot, V
Nchot, C
Karcher, S
Chaix, ML
Rouzioux, C
Sow, PS
Perronne, C
Girard, PM
Menan, H
Bissagnene, E
Kadio, A
Ettiegne-Traore, V
Moh-Semdé, C
Kouame, A
Massumbuko, JM
Chêne, G
Dosso, M
Domoua, SK
N'Dri-Yoman, T
Salamon, R
Eholié, SP
Anglaret, X
Item Type: Journal Article
Abstract: BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.).
Issue Date: 27-Aug-2015
Date of Acceptance: 1-Aug-2015
URI: http://hdl.handle.net/10044/1/41218
DOI: http://dx.doi.org/10.1056/NEJMoa1507198
ISSN: 1533-4406
Publisher: Massachusetts Medical Society
Start Page: 808
End Page: 822
Journal / Book Title: New England Journal of Medicine
Volume: 373
Issue: 9
Copyright Statement: From N Engl J Med 2015; 373:808-822 © 2015 Massachusetts Medical Society. Reprinted with permission.
Keywords: AIDS-Related Opportunistic Infections
Adult
Anti-Retroviral Agents
Antitubercular Agents
Asymptomatic Diseases
CD4 Lymphocyte Count
Cote d'Ivoire
Female
Follow-Up Studies
HIV Infections
HIV-1
Humans
Isoniazid
Male
Middle Aged
RNA, Viral
Time-to-Treatment
Tuberculosis
Viral Load
TEMPRANO ANRS 12136 Study Group
General & Internal Medicine
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:School of Public Health