S E Collins1, M A Jean Juste2, S P Koenig3, R Secours2, O Ocheretina1, D Bernard2, C Riviere2, M Calnan4, A Dunning5, S M Hurtado Rúa5, W D Johnson1, J W Pape6, D W Fitzgerald1, P Severe2. 1. Center for Global Health, Department of Medicine, Weill Cornell Medical College, New York, New York, USA. 2. Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO), Port au Prince, Haiti. 3. Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, USA. 4. Analysis Group, Inc. Boston, Massachusetts, USA. 5. Department of Public Health, Weill Cornell Medical College, New York, New York, USA. 6. Center for Global Health, Department of Medicine, Weill Cornell Medical College, New York, New York, USA; Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO), Port au Prince, Haiti.
Abstract
SETTING: Port-au-Prince, Haiti. OBJECTIVE: To determine long-term effects of early vs. delayed initiation of antiretroviral therapy (ART) on immune recovery and tuberculosis (TB) risk in human immunodeficiency virus (HIV) infected individuals. DESIGN: Open-label randomized controlled trial of immediate ART in HIV-infected adults with CD4 counts between 200 and 350 cells/mm(3) vs. deferring ART until the CD4 count was <200 cells/mm(3). The primary comparisons were CD4 counts over time and risk for incident TB, with 5 years of follow-up. RESULTS: A total of 816 participants were enrolled, with 408 in each treatment arm. The early treatment group started ART within 2 weeks, while the deferred treatment group started ART a median of 1.3 years after enrollment. After 5 years, the mean CD4 count in the early treatment group was significantly higher than in the deferred treatment group (496 cells/mm(3), 95% confidence interval [CI] 477-515 vs. 373 cells/mm(3), 95%CI 357-389; P < 0.0001). TB risk was higher in the deferred treatment group (unadjusted HR 2.41, 95%CI 1.56-3.74; P < 0.0001) and strongly correlated with lower CD4 counts in time-dependent multivariate analysis. CONCLUSION: Delays in ART initiation for HIV-infected adults with CD4 counts of 200-350 cells/mm(3) can result in long-term immune dysfunction and persistent increased risk for TB.
RCT Entities:
SETTING: Port-au-Prince, Haiti. OBJECTIVE: To determine long-term effects of early vs. delayed initiation of antiretroviral therapy (ART) on immune recovery and tuberculosis (TB) risk in human immunodeficiency virus (HIV) infected individuals. DESIGN: Open-label randomized controlled trial of immediate ART in HIV-infected adults with CD4 counts between 200 and 350 cells/mm(3) vs. deferring ART until the CD4 count was <200 cells/mm(3). The primary comparisons were CD4 counts over time and risk for incident TB, with 5 years of follow-up. RESULTS: A total of 816 participants were enrolled, with 408 in each treatment arm. The early treatment group started ART within 2 weeks, while the deferred treatment group started ART a median of 1.3 years after enrollment. After 5 years, the mean CD4 count in the early treatment group was significantly higher than in the deferred treatment group (496 cells/mm(3), 95% confidence interval [CI] 477-515 vs. 373 cells/mm(3), 95%CI 357-389; P < 0.0001). TB risk was higher in the deferred treatment group (unadjusted HR 2.41, 95%CI 1.56-3.74; P < 0.0001) and strongly correlated with lower CD4 counts in time-dependent multivariate analysis. CONCLUSION: Delays in ART initiation for HIV-infected adults with CD4 counts of 200-350 cells/mm(3) can result in long-term immune dysfunction and persistent increased risk for TB.
Authors: Yvetot Joseph; Zhiwen Yao; Akanksha Dua; Patrice Severe; Sean E Collins; Heejung Bang; Marc Antoine Jean-Juste; Oksana Ocheretina; Alexandra Apollon; Margaret L McNairy; Kathryn Dupnik; Etienne Cremieux; Anthony Byrne; Jean W Pape; Serena P Koenig Journal: J Int AIDS Soc Date: 2021-07 Impact factor: 5.396
Authors: Henry Kanyerere; Anthony D Harries; Katie Tayler-Smith; Andreas Jahn; Rony Zachariah; Frank M Chimbwandira; James Mpunga Journal: Trop Med Int Health Date: 2015-11-16 Impact factor: 2.622
Authors: Maia Lesosky; Molebogeng X Rangaka; Cara Pienaar; Anna K Coussens; Rene Goliath; Shaheed Mathee; Judith Mwansa-Kambafwile; Gary Maartens; Robert J Wilkinson; Katalin Andrea Wilkinson Journal: Clin Infect Dis Date: 2019-07-02 Impact factor: 9.079