Earlier versus Later Start of Antiretroviral Therapy in HIV-Infected Adults with Tuberculosis
Year: 2011
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUND: Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy. METHODS: We tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower. After beginning the standard, 6-month treatment for tuberculosis, patients were randomly assigned to either earlier treatment (2 weeks after beginning tuberculosis treatment) or later treatment (8 weeks after) with stavudine, lamivudine, and efavirenz. The primary end point was survival. RESULTS: A total of 661 patients were enrolled and were followed for a median of 25 months. The median CD4+ T-cell count was 25 per cubic millimeter, and the median viral load was 5.64 log(10) copies per milliliter. The risk of death was significantly reduced in the group that received ART earlier, with 59 deaths among 332 patients (18%), as compared with 90 deaths among 329 patients (27%) in the later-ART group (hazard ratio, 0.62; 95% confidence interval [CI]; 0.44 to 0.86; P=0.006). The risk of tuberculosis-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group (hazard ratio, 2.51; 95% CI, 1.78 to 3.59; P<0.001). Irrespective of the study group, the median gain in the CD4+ T-cell count was 114 per cubic millimeter, and the viral load was undetectable at week 50 in 96.5% of the patients. CONCLUSIONS: Initiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4+ T-cell counts of 200 per cubic millimeter or lower. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis and the National Institutes of Health; CAMELIA ClinicalTrials.gov number, NCT01300481.).
Source: New England Journal of Medicine
Authors: François-Xavier Blanc, Thim Sok, Didier Laureillard, Laurence Borand, Claire Rekacewicz, Eric Nerrienet, Yoann Madec, Olivier Marcy, Sarin Chan, Narom Prak, Chindamony Kim, Khemarin Kim Lak, Chanroeurn Hak, Bunnet Dim, Chhun Im Sin, Sath Sun, Bertrand Guillard, Borann Sar, Sirenda Vong, Marcelo Fernandez, Lawrence Fox, Jean-François Delfraissy, Anne E. Goldfeld
Institutions: Assistance Publique – Hôpitaux de Paris, Bicêtre Hospital, Hôpital Européen Georges-Pompidou, Institut Pasteur du Cambodge, Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Institut Pasteur, Ministry of Health, Médecins Sans Frontières, Médecins Sans Frontières, Médecins Sans Frontières, Médecins Sans Frontières, Chaiyaphum Hospital, Rayong Hospital, Roi Et Hospital, Calmette Hospital, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Inserm, Harvard University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Annenberg Foundation, Bristol-Myers Squibb, GlaxoSmithKline, Gilead Sciences, Aeras Global Tuberculosis Vaccine Foundation, Agence Nationale de Recherches sur le Sida et les Hépatites Virales, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Environmental Health Sciences, CHIST-ERA
OpenAlex ID: W2151102304