BACKGROUND Identifying factors that predict the timing of HIV rebound after treatment interruption will be crucial for designing and evaluating interventions for HIV remission.METHODS We performed a broad evaluation of viral and immune factors that predict viral rebound (AIDS Clinical Trials Group A5345). Participants initiated antiretroviral therapy (ART) during chronic (N = 33) or early (N = 12) HIV infection with ≥ 2 years of suppressive ART and restarted ART if they had 2 viral loads ≥ 1,000 copies/mL after treatment interruption.RESULTS Compared with chronic-treated participants, early-treated individuals had smaller and fewer transcriptionally active HIV reservoirs. A higher percentage of HIV Gag-specific CD8+ T cell cytotoxic response was associated with lower intact proviral DNA. Predictors of HIV rebound timing differed between early- versus chronic-treated participants, as the strongest reservoir predictor of time to HIV rebound was level of residual viremia in early-treated participants and intact DNA level in chronic-treated individuals. We also identified distinct sets of pre–treatment interruption viral, immune, and inflammatory markers that differentiated participants who had rapid versus slow rebound.CONCLUSION The results provide an in-depth overview of the complex interplay of viral, immunologic, and inflammatory predictors of viral rebound and demonstrate that the timing of ART initiation modifies the features of rapid and slow viral rebound.TRIAL REGISTRATION ClinicalTrials.gov NCT03001128FUNDING NIH National Institute of Allergy and Infectious Diseases, Merck
Jonathan Z. Li, Meghan Melberg, Autumn Kittilson, Mohamed Abdel-Mohsen, Yijia Li, Evgenia Aga, Ronald J. Bosch, Elizabeth R. Wonderlich, Jennifer Kinslow, Leila B. Giron, Clara Di Germanio, Mark Pilkinton, Lynsay MacLaren, Michael Keefer, Lawrence Fox, Liz Barr, Edward Acosta, Jintanat Ananworanich, Robert Coombs, John Mellors, Steven Deeks, Rajesh T. Gandhi, Michael Busch, Alan Landay, Bernard Macatangay, Davey M. Smith, for the AIDS Clinical Trials Group A5345 Study Team
This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.