TY - JOUR
T1 - Predictors of HIV rebound differ by timing of antiretroviral therapy initiation
AU - Li, Jonathan Z.
AU - Melberg, Meghan
AU - Kittilson, Autumn
AU - Abdel-Mohsen, Mohamed
AU - Li, Yijia
AU - Aga, Evgenia
AU - Bosch, Ronald J.
AU - Wonderlich, Elizabeth R.
AU - Kinslow, Jennifer
AU - Giron, Leila B.
AU - Di Germanio, Clara
AU - Pilkinton, Mark
AU - MacLaren, Lynsay
AU - Keefer, Michael
AU - Fox, Lawrence
AU - Barr, Liz
AU - Acosta, Edward
AU - Ananworanich, Jintanat
AU - Coombs, Robert
AU - Mellors, John
AU - Deeks, Steven
AU - Gandhi, Rajesh T.
AU - Busch, Michael
AU - Landay, Alan
AU - Macatangay, Bernard
AU - Smith, Davey M.
N1 - Publisher Copyright:
© 2024, Li et al.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
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U2 - 10.1172/jci.insight.173864
DO - 10.1172/jci.insight.173864
M3 - Article
C2 - 38329130
AN - SCOPUS:85184714489
SN - 2379-3708
VL - 9
JO - JCI insight
JF - JCI insight
IS - 3
M1 - e173864
ER -