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 Fernandez, Lawrence Fox, Jean-François Delfraissy, Anne E Goldfeld, CAMELIA (ANRS 1295–CIPRA KH001) Study Team, Manil Saman, Chanthy Leng, Sao Sarady Ay, Phalla Chea, Phearavin Pheng, Lay Heng Chan, Sophea Soum, Nimul Roat Men, Kerya Phon, Sopheap Kun, Sokeo Chea, Pichda Toeung, Yong Yoeun, Keo Kunthea Dy, Pheakun Kry, Keolinelyanneth Meardey, Chanthan Srey, Chantary Keo, Sopheak Ngin, Janin Nouhin, Sreymom Ken, Kimlay Chea, Kunthea Kong, Sophy Tun, Leakhena Say, Kim Eng Sok, Hok Kean Lim, Chou Monidarin, Chan Chhaya Nget, Sor Kaing, Sovannara Song, Bora Am, Sok Cheung, Tuon Seang Y, Seng Ly Say, Sarann Sum, Seam Chhun, Vanny Say, Sokhoeun Kam, Chanthan Ung, Nai Sim Te, Sokim Chhoeun, Chuop Chum Koh, Ratanak Tong, Cheung Sok, Saorin Tith, Sithan Chan, Sean Yim, Nimul Chan Ear, Dara Chan, Sokbophang Voeung, Phally Be, Chan Nimul Ear, Vanda Prak, Thoeurn Men, Thoeun Koy, Somaly Thach, Sinan Chhay, Sina Meas, Vara Ouk, Thavary Saem, Boroath Ban, Sreng Setha Lim, Chheng Lang Kao, Ra Chheang, Tay Kry Heng, Socheatana Ly, Rano Sok, Sam Aun Pao, Thieng Van, Seng Sokunthea Kaing, Chheng Lang Kao, Vannath Khin, Phany Ing, Sotheary Chea, Thong Phe, Saroeun Uorng, Sokhon Kuoch, Phea Lao, Chanthan Yim, Samros Khiev, Sareth Hem, Kimthan Keo, Samoeun Um, Sophary Teang, Yimtheavy Me, Chanthon Yim, Bunthoeun Heang, Hort Sieng, Huch Meas, Sina Sok, Vibol Neak, Nyn Ken, Kunthea Tes, Soeun San, Soeun Sean, Say Chy, Sothy Sor, Tol Samret, Posson Tan, Putchhat Hor, Phalkun Pen, Bophary Lmuth, Soarath Chay, Tin Choun, Vuthin Rem, Bona Noeuth, Sovannveary Chhuom, Sothearoth Sourn, Thol Lim, Sun Dara Preab, Phay Un, Put Chat Hor, Somnang Man, Kong Srey, Sen Bun, Manory Oum, 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, CAMELIA (ANRS 1295–CIPRA KH001) Study Team, Manil Saman, Chanthy Leng, Sao Sarady Ay, Phalla Chea, Phearavin Pheng, Lay Heng Chan, Sophea Soum, Nimul Roat Men, Kerya Phon, Sopheap Kun, Sokeo Chea, Pichda Toeung, Yong Yoeun, Keo Kunthea Dy, Pheakun Kry, Keolinelyanneth Meardey, Chanthan Srey, Chantary Keo, Sopheak Ngin, Janin Nouhin, Sreymom Ken, Kimlay Chea, Kunthea Kong, Sophy Tun, Leakhena Say, Kim Eng Sok, Hok Kean Lim, Chou Monidarin, Chan Chhaya Nget, Sor Kaing, Sovannara Song, Bora Am, Sok Cheung, Tuon Seang Y, Seng Ly Say, Sarann Sum, Seam Chhun, Vanny Say, Sokhoeun Kam, Chanthan Ung, Nai Sim Te, Sokim Chhoeun, Chuop Chum Koh, Ratanak Tong, Cheung Sok, Saorin Tith, Sithan Chan, Sean Yim, Nimul Chan Ear, Dara Chan, Sokbophang Voeung, Phally Be, Chan Nimul Ear, Vanda Prak, Thoeurn Men, Thoeun Koy, Somaly Thach, Sinan Chhay, Sina Meas, Vara Ouk, Thavary Saem, Boroath Ban, Sreng Setha Lim, Chheng Lang Kao, Ra Chheang, Tay Kry Heng, Socheatana Ly, Rano Sok, Sam Aun Pao, Thieng Van, Seng Sokunthea Kaing, Chheng Lang Kao, Vannath Khin, Phany Ing, Sotheary Chea, Thong Phe, Saroeun Uorng, Sokhon Kuoch, Phea Lao, Chanthan Yim, Samros Khiev, Sareth Hem, Kimthan Keo, Samoeun Um, Sophary Teang, Yimtheavy Me, Chanthon Yim, Bunthoeun Heang, Hort Sieng, Huch Meas, Sina Sok, Vibol Neak, Nyn Ken, Kunthea Tes, Soeun San, Soeun Sean, Say Chy, Sothy Sor, Tol Samret, Posson Tan, Putchhat Hor, Phalkun Pen, Bophary Lmuth, Soarath Chay, Tin Choun, Vuthin Rem, Bona Noeuth, Sovannveary Chhuom, Sothearoth Sourn, Thol Lim, Sun Dara Preab, Phay Un, Put Chat Hor, Somnang Man, Kong Srey, Sen Bun, Manory Oum
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.).
Conflict of interest statement
No other potential conflict of interest relevant to this article was reported.
Figures
Source: PubMed