Impact of antiretroviral therapy during acute or early HIV infection on virologic and immunologic outcomes: results from a multinational clinical trial.
| Autor: | Crowell TA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland., Ritz J; Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Zheng L; Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Naqvi A; University of Pittsburgh, Pittsburgh, Pennsylvania., Cyktor JC; University of Pittsburgh, Pittsburgh, Pennsylvania., Puleo J; Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Clagett B; Case Western Reserve University, Cleveland, Ohio, USA., Lama JR; Asociación Civil Impacta Salud y Educación, Lima, Peru., Kanyama C; University of North Carolina Project, Lilongwe, Malawi., Little SJ; University of California San Diego, San Diego, California., Cohn SE; Northwestern University Feinberg School of Medicine, Chicago, Illinois., Riddler SA; University of Pittsburgh, Pittsburgh, Pennsylvania., Collier AC; University of Washington, Seattle, Washington., Heath SL; University of Alabama @ Birmingham, Birmingham, Alabama, USA., Tantivitayakul P; SEARCH Foundation, Bangkok, Thailand., Grinsztejn B; Institute de Pesquisa Clinica Evandro Chagas, Rio de Janeiro, Brazil., Arduino RC; McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas., Rooney JF; Gilead Sciences, Foster City, California, USA., van Zyl GU; Stellenbosch University, Cape Town, South Africa., Coombs RW; University of Washington, Seattle, Washington., Fox L; Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA., Ananworanich J; Amsterdam UMC, Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands., Eron JJ; University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Sieg SF; Case Western Reserve University, Cleveland, Ohio, USA., Mellors JW; University of Pittsburgh, Pittsburgh, Pennsylvania., Daar ES; Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA. |
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| Jazyk: | angličtina |
| Zdroj: | AIDS (London, England) [AIDS] 2024 Jul 01; Vol. 38 (8), pp. 1141-1152. Date of Electronic Publication: 2024 Mar 13. |
| DOI: | 10.1097/QAD.0000000000003881 |
| Abstrakt: | 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. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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