Predictors of HIV rebound differ by timing of antiretroviral therapy initiation

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 MellorsSteven Deeks, Rajesh T. Gandhi, Michael Busch, Alan Landay, Bernard Macatangay, Davey M. Smith

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbere173864
JournalJCI insight
Issue number3
StatePublished - 2024
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine


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