The setpoint study (ACTG A5217): effect of immediate versus deferred antiretroviral therapy on virologic set point in recently HIV-1-infected individuals
Christine M Hogan, Victor Degruttola, Xin Sun, Susan A Fiscus, Carlos Del Rio, C Bradley Hare, Martin Markowitz, Elizabeth Connick, Bernard Macatangay, Karen T Tashima, Beatrice Kallungal, Rob Camp, Tia Morton, Eric S Daar, Susan Little, A5217 Study Team, Roula Qaqish, James Rooney, David Currin, Ana Martinez, Rick Hecht, Donna Mildvan, Charles Rinaldo, Karen Messer, Florin Vaida, M Graham Ray, Beverly Putnam, Aaron Diamond, Michael F Para, Kathy J Watson, Joanne Santangelo, Dee Dee Pacheco, Pamela Poethke, Janine Maenza, Claire Stevens, Ge-Youl Kim, Michael K Klebert, Pablo Tebas, Joseph Quinn, Margaret A, Hector Bolivar, Karen Coleman, Baiba Berzins, Timothy Lane, Kim Epperson RN, Mario Guerrero, Sadia Shaik, Javier R Lama, Donna Pittard, Susan Pedersen, Mary Adams, Allan S Tenorio, Beverly E Sha, C Bradley, Deborah Zeitschel, Susan Aileen Olender, Chrisa Hunnewell, Madeline Torres, Eric Rosenberg, Amy Sbrolla, Teri Flynn, Charles E Davis, William Blattner, Juan V Guanira, Christine Hurley, Roberto Corales, Molly Eaton, Ericka Patrick, Mark Byroads, Christine M Hogan, Victor Degruttola, Xin Sun, Susan A Fiscus, Carlos Del Rio, C Bradley Hare, Martin Markowitz, Elizabeth Connick, Bernard Macatangay, Karen T Tashima, Beatrice Kallungal, Rob Camp, Tia Morton, Eric S Daar, Susan Little, A5217 Study Team, Roula Qaqish, James Rooney, David Currin, Ana Martinez, Rick Hecht, Donna Mildvan, Charles Rinaldo, Karen Messer, Florin Vaida, M Graham Ray, Beverly Putnam, Aaron Diamond, Michael F Para, Kathy J Watson, Joanne Santangelo, Dee Dee Pacheco, Pamela Poethke, Janine Maenza, Claire Stevens, Ge-Youl Kim, Michael K Klebert, Pablo Tebas, Joseph Quinn, Margaret A, Hector Bolivar, Karen Coleman, Baiba Berzins, Timothy Lane, Kim Epperson RN, Mario Guerrero, Sadia Shaik, Javier R Lama, Donna Pittard, Susan Pedersen, Mary Adams, Allan S Tenorio, Beverly E Sha, C Bradley, Deborah Zeitschel, Susan Aileen Olender, Chrisa Hunnewell, Madeline Torres, Eric Rosenberg, Amy Sbrolla, Teri Flynn, Charles E Davis, William Blattner, Juan V Guanira, Christine Hurley, Roberto Corales, Molly Eaton, Ericka Patrick, Mark Byroads
Abstract
Background: The benefits of antiretroviral therapy during early human immunodeficiency virus type 1 (HIV-1) infection remain unproved.
Methods: A5217 study team randomized patients within 6 months of HIV-1 seroconversion to receive either 36 weeks of antiretrovirals (immediate treatment [IT]) or no treatment (deferred treatment [DT]). Patients were to start or restart antiretroviral therapy if they met predefined criteria. The primary end point was a composite of requiring treatment or retreatment and the log(10) HIV-1 RNA level at week 72 (both groups) and 36 (DT group).
Results: At the June 2009 Data Safety Monitoring Board (DSMB) review, 130 of 150 targeted participants had enrolled. Efficacy analysis included 79 individuals randomized ≥72 weeks previously. For the primary end point, the IT group at week 72 had a better outcome than the DT group at week 72 (P = .005) and the DT group at week 36 (P = .002). The differences were primarily due to the higher rate of progression to needing treatment in the DT group (50%) versus the IT (10%) group. The DSMB recommended stopping the study because further follow-up was unlikely to change these findings.
Conclusions: Progression to meeting criteria for antiretroviral initiation in the DT group occurred more frequently than anticipated, limiting the ability to evaluate virologic set point. Antiretrovirals during early HIV-1 infection modestly delayed the need for subsequent treatment.
Clinical trials registration: NCT00090779.
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Source: PubMed