Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis

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 FernandezLawrence Fox, Jean François Delfraissy, Anne E. Goldfeld

Research output: Contribution to journalArticlepeer-review

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 log10 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.)

Original languageEnglish (US)
Pages (from-to)1471-1481
Number of pages11
JournalNew England Journal of Medicine
Volume365
Issue number16
DOIs
StatePublished - Oct 20 2011
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine

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