BACKGROUND: The rates of death are high among patients with coinfection with tuberculosis and the human immunodeficiency virus (HIV). The optimal timing for the initiation of antiretroviral therapy in relation to tuberculosis therapy remains controversial. METHODS: In an open-label, randomized, controlled trial in Durban, South Africa, we assigned 642 patients with both tuberculosis and HIV infection to start antiretroviral therapy either during tuberculosis therapy (in two integrated-therapy groups) or after the completion of such treatment (in one sequential-therapy group). The diagnosis of tuberculosis was based on a positive sputum smear for acid-fast bacilli. Only patients with HIV infection and a CD4+ cell count of less than 500 per cubic millimeter were included. All patients received standard tuberculosis therapy, prophylaxis with trimethoprim-sulfamethoxazole, and a once-daily antiretroviral regimen of didanosine, lamivudine, and efavirenz. The primary end point was death from any cause. RESULTS: This analysis compares data from the sequential-therapy group and the combined integrated-therapy groups up to September 1, 2008, when the data and safety monitoring committee recommended that all patients receive integrated antiretroviral therapy. There was a reduction in the rate of death among the 429 patients in the combined integrated-therapy groups (5.4 deaths per 100 person-years, or 25 deaths), as compared with the 213 patients in the sequential-therapy group (12.1 per 100 person-years, or 27 deaths); a relative reduction of 56% (hazard ratio in the combined integrated-therapy groups, 0.44; 95% confidence interval, 0.25 to 0.79; P=0.003). Mortality was lower in the combined integrated-therapy groups in all CD4+ count strata. Rates of adverse events during follow-up were similar in the two study groups. CONCLUSIONS: The initiation of antiretroviral therapy during tuberculosis therapy significantly improved survival and provides further impetus for the integration of tuberculosis and HIV services. (ClinicalTrials.gov number, NCT00398996.) 2010 Massachusetts Medical Society
RCT Entities:
BACKGROUND: The rates of death are high among patients with coinfection with tuberculosis and the human immunodeficiency virus (HIV). The optimal timing for the initiation of antiretroviral therapy in relation to tuberculosis therapy remains controversial. METHODS: In an open-label, randomized, controlled trial in Durban, South Africa, we assigned 642 patients with both tuberculosis and HIV infection to start antiretroviral therapy either during tuberculosis therapy (in two integrated-therapy groups) or after the completion of such treatment (in one sequential-therapy group). The diagnosis of tuberculosis was based on a positive sputum smear for acid-fast bacilli. Only patients with HIV infection and a CD4+ cell count of less than 500 per cubic millimeter were included. All patients received standard tuberculosis therapy, prophylaxis with trimethoprim-sulfamethoxazole, and a once-daily antiretroviral regimen of didanosine, lamivudine, and efavirenz. The primary end point was death from any cause. RESULTS: This analysis compares data from the sequential-therapy group and the combined integrated-therapy groups up to September 1, 2008, when the data and safety monitoring committee recommended that all patients receive integrated antiretroviral therapy. There was a reduction in the rate of death among the 429 patients in the combined integrated-therapy groups (5.4 deaths per 100 person-years, or 25 deaths), as compared with the 213 patients in the sequential-therapy group (12.1 per 100 person-years, or 27 deaths); a relative reduction of 56% (hazard ratio in the combined integrated-therapy groups, 0.44; 95% confidence interval, 0.25 to 0.79; P=0.003). Mortality was lower in the combined integrated-therapy groups in all CD4+ count strata. Rates of adverse events during follow-up were similar in the two study groups. CONCLUSIONS: The initiation of antiretroviral therapy during tuberculosis therapy significantly improved survival and provides further impetus for the integration of tuberculosis and HIV services. (ClinicalTrials.gov number, NCT00398996.) 2010 Massachusetts Medical Society
Authors: E Girardi; F Palmieri; A Cingolani; A Ammassari; N Petrosillo; L Gillini; D Zinzi; A De Luca; A Antinori; G Ippolito Journal: J Acquir Immune Defic Syndr Date: 2001-04-01 Impact factor: 3.731
Authors: P García de Olalla; M A Martínez-González; J A Caylà; J M Jansà; B Iglesias; R Guerrero; A Marco; J M Gatell; I Ocaña Journal: Int J Tuberc Lung Dis Date: 2002-12 Impact factor: 2.373
Authors: Graeme Meintjes; Molebogeng X Rangaka; Gary Maartens; Kevin Rebe; Chelsea Morroni; Dominique J Pepper; Katalin A Wilkinson; Robert J Wilkinson Journal: Clin Infect Dis Date: 2009-03-01 Impact factor: 9.079
Authors: Jonathan A C Sterne; Margaret May; Dominique Costagliola; Frank de Wolf; Andrew N Phillips; Ross Harris; Michele Jönsson Funk; Ronald B Geskus; John Gill; François Dabis; Jose M Miró; Amy C Justice; Bruno Ledergerber; Gerd Fätkenheuer; Robert S Hogg; Antonella D'Arminio Monforte; Michael Saag; Colette Smith; Schlomo Staszewski; Matthias Egger; Stephen R Cole Journal: Lancet Date: 2009-04-08 Impact factor: 79.321
Authors: J C M Brust; N S Shah; M Scott; K Chaiyachati; M Lygizos; T L van der Merwe; S Bamber; Z Radebe; M Loveday; A P Moll; B Margot; U G Lalloo; G H Friedland; N R Gandhi Journal: Int J Tuberc Lung Dis Date: 2012-06-05 Impact factor: 2.373
Authors: Douglas C Heimburger; Catherine Lem Carothers; Pierce Gardner; Aron Primack; Tokesha L Warner; Sten H Vermund Journal: Am J Trop Med Hyg Date: 2011-12 Impact factor: 2.345
Authors: J Hafkin; C Modongo; C Newcomb; E Lowenthal; R R MacGregor; A P Steenhoff; H Friedman; G P Bisson Journal: Int J Tuberc Lung Dis Date: 2013-01-14 Impact factor: 2.373