Impact of Antiretroviral Therapy During Acute or Early HIV Infection on Virologic and Immunologic Outcomes: Results From a Multinational Clinical Trial

Authors

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

Language

English

Publication Date

7-1-2024

Journal

AIDS

DOI

10.1097/QAD.0000000000003881

PMID

38489580

PMCID

PMC11323228

PubMedCentral® Posted Date

7-1-2025

PubMedCentral® Full Text Version

Author MSS

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.

Keywords

Humans, HIV Infections, Female, Adult, Male, Young Adult, Anti-Retroviral Agents, Viral Load, CD4-Positive T-Lymphocytes, DNA, Viral, Treatment Outcome, Asia, Africa

Published Open-Access

yes

Recommended Citation

Crowell, Trevor A; Ritz, Justin; Zheng, Lu; et al., "Impact of Antiretroviral Therapy During Acute or Early HIV Infection on Virologic and Immunologic Outcomes: Results From a Multinational Clinical Trial" (2024). Faculty, Staff and Student Publications. 3530.
https://digitalcommons.library.tmc.edu/uthmed_docs/3530