Impact of antiretroviral therapy during acute or early HIV infection on virologic and immunologic outcomes: results from a multinational clinical trial

OBJECTIVE: To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses. DESIGN: Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia. METHODS: HIV DNA was measured at week 48 of ART in 5 million CD4 + T cells by sensitive qPCR assays targeting HIV gag and pol . Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env , gag , nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines. RESULTS: From 2017 to 2019, 188 participants initiated ART during Fiebig stages I ( n = 6), II ( n = 43), III ( n = 56), IV ( n = 23), and V ( n = 60). Median age was 27 years (interquartile range 23-38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels ( P < 0.001). Week 48 HIV DNA mostly did not correlate with concurrent CD4 + or CD8 + T cell HIV-specific immune responses (rho range -0.11 to +0.19, all P > 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest. CONCLUSION: Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods.

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Publication Details

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UNC Libraries
Published
2025-03-14
DOI
https://doi.org/10.17615/617b-mq21
Primary Topic
HIV Research and Treatment
Type
article
Field-Weighted Citation Impact
0.00

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article

Impact of antiretroviral therapy during acute or early HIV infection on virologic and immunologic outcomes: results from a multinational clinical trial

Javier R. Lama, Sonya L. Heath, Sharon A. Riddler, Joseph Puleo et al.
UNC Libraries
HIV Research and Treatment
article

Impact of antiretroviral therapy during acute or early HIV infection on virologic and immunologic outcomes: results from a multinational clinical trial

Javier R. Lama, Sonya L. Heath, Sharon A. Riddler, Joseph Puleo, Asma Naqvi, Joseph J. Eron, Beatriz Gilda Jegerhorn Grinsztejn, Gert Uves van Zyl, Susan J. Little, Roberto C. Arduino, John W. Mellors, Scott F. Sieg, Brian Clagett, Susan E. Cohn, James F. Rooney, Joshua C. Cyktor, Jintanat Ananworanich, Robert W. Coombs, Trevor A. Crowell, Eric S. Daar, Justin Ritz, Lu Zheng, Cecilia Kanyama, Ann C. Collier, Pornphen Tantivitayakul, Lawrence Fox, and the SAPALDIA Team
article en

Abstract

OBJECTIVE: To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses. DESIGN: Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia. METHODS: HIV DNA was measured at week 48 of ART in 5 million CD4 + T cells by sensitive qPCR assays targeting HIV gag and pol . Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env , gag , nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines. RESULTS: From 2017 to 2019, 188 participants initiated ART during Fiebig stages I ( n = 6), II ( n = 43), III ( n = 56), IV ( n = 23), and V ( n = 60). Median age was 27 years (interquartile range 23-38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels ( P < 0.001). Week 48 HIV DNA mostly did not correlate with concurrent CD4 + or CD8 + T cell HIV-specific immune responses (rho range -0.11 to +0.19, all P > 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest. CONCLUSION: Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods.

UNC Libraries
University of North Carolina at Chapel Hill (US)
U.S. Department of Defense, U.S. Department of Health and Human Services, Brigham and Women's Hospital, Massachusetts General Hospital, Gilead Sciences, University of Pennsylvania, Ohio State University, Northwestern University, University of Washington, Rush University, ACT Government, National Institutes of Health, University of California, Los Angeles, Weill Cornell Medical College, University of California, San Diego, National Institute of Allergy and Infectious Diseases
Openalex Percentile: Top 65%
HIV Research and Treatment
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