Antiretroviral Therapy Intensification With Dolutegravir and/or Maraviroc Did Not Affect HIV-1 Cell-Associated DNA, RNA, and 2–LTR Circles Over 12 Weeks
Year: 2025
Type: article
Abstract: Background Neurocognitive impairment (NCI) among people living with human immunodeficiency virus (HIV; PWH) on antiretroviral therapy (ART) may result from residual viral replication. The A5324 trial found that ART intensification with dolutegravir (DTG) with or without maraviroc (MVC) did not affect NCI in PWH. We evaluated the impact of ART intensification on peripheral virological measures during the first 12 weeks of intensification. Methods The A5324 study was a randomized, double-blind, placebo (PBO)–controlled, 96-week trial of ART intensification with either dual PBO, DTG + PBO, or DTG + MVC in PWH with NCI on ART who were naive to integrase strand transfer inhibitors and MVC. At baseline and weeks 2, 4, and 12, HIV-1 RNA was measured in plasma with a low-copy assay, while HIV-1 cell-associated DNA (caDNA), cell-associated unspliced RNA (caRNA), and cell-associated 2-long terminal repeat circles (ca2LTR) were quantified from peripheral blood mononuclear cells using droplet digital polymerase chain reaction. Results Of the 171 participants, 59 were randomized to dual PBO, 57 to DTG + PBO, and 55 to DTG + MVC. Changes in caDNA and caRNA and detection of plasma RNA did not differ between treatment arms over 12 weeks (P > 0.05). Detection of ca2LTR was less frequent at weeks 2–4 in the DTG + MVC arm (40.4%) than in the dual-PBO (70.7%; P =0 .02) and DTG + PBO (68.4%; P = 0.03) arms. However, this difference diminished by week 12, and baseline ca2LTR detection in the DTG + MVC arm was lower than in the other groups. Conclusions DTG intensification had no effect on peripheral markers of HIV-1 persistence. DTG + MVC intensification reduced ca2LTR detection at weeks 2–4, though this effect did not persist through week 12. These findings indicate the minimal impact of intensification on the HIV-1 peripheral reservoir, consistent with prior studies.
Source: Open Forum Infectious Diseases
DOI: 10.1093/ofid/ofaf594
Authors: Jonathan C Reed, Luke Hall, Ashley McKhann, Ginger Kwak, Erin A Goecker, Robert W Coombs, Huichao Chen, Jhoanna Roa, Alyssa Vecchio, Eric S Daar, Peter W Hunt, Christina M Marra, Thomas B Campbell, Qing Ma, Shobha Swaminathan, Bernard J C Macatangay, Gene D Morse, Thomas Miller, David Rusin, Belinda Ha, Beverly Alston-Smith, Robert Paul, Scott L Letendre, Serena S Spudich, Alexander L Greninger
Institutions: University of Washington, Harvard University, DLH Corporation (United States), University of North Carolina at Chapel Hill, University of California, Los Angeles, The Lundquist Institute, Los Angeles Medical Center, University of California, San Francisco, University of Colorado Anschutz, University of Colorado Denver, University at Buffalo, State University of New York, Rutgers New Jersey Medical School, University of Pittsburgh, Frontier Science & Technology Research Foundation, Inc., National Institutes of Health, Office of AIDS Research, University of Missouri–St. Louis, University of California San Diego, Yale University, Fred Hutch Cancer Center
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,053
Awards: G2548217053, G374818150, G378552126, Weill Cornell Medicine - Rutgers New Jersey Medical School Clinical Trials Unit, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, Statistical and Data Management Center (SDMC), Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG), Seattle Clinical Trials Unit
OpenAlex ID: W4414687771