Acute HIV-1 infection viremia associate with rebound upon treatment interruption

• Published in: Med (New York, N.Y. : Online) Vol. 3; no. 9; pp. 622 - 635.e3
• Main Authors: Mdluli, Thembi, Li, Yifan, Pinyakorn, Suteeraporn, Reeves, Daniel B, Cardozo-Ojeda, E Fabian, Yates, Adam, Intasan, Jintana, Tipsuk, Somporn, Phanuphak, Nittaya, Sacdalan, Carlo, Colby, Donn J, Kroon, Eugène, Crowell, Trevor A, Thomas, Rasmi, Robb, Merlin L, Ananworanich, Jintanat, de Souza, Mark, Phanuphak, Praphan, Stieh, Daniel J, Tomaka, Frank L, Trautmann, Lydie, Ake, Julie A, Hsu, Denise C, Francisco, Leilani V, Vasan, Sandhya, Rolland, Morgane
• Format: Journal Article
• Language: English
• Published: United States 09.09.2022
• Subjects: Anti-Retroviral Agents - therapeutic use; HIV Infections - drug therapy; HIV-1; Humans; Viral Load; Viremia - drug therapy; correlates of HIV-1 rebound; HIV-1 cure; Translation to patients; HIV-1 acute infection; analytic treatment interruption
• ISSN: 2666-6340; 2666-6359; 2666-6340
• DOI: 10.1016/j.medj.2022.06.009

Analytic treatment interruption (ATI) studies evaluate strategies to potentially induce remission in people living with HIV-1 but are often limited in sample size. We combined data from four studies that tested three interventions (vorinostat/hydroxychloroquine/maraviroc before ATI, Ad26/MVA vaccination before ATI, and VRC01 antibody infusion during ATI). The statistical validity of combining data from these participants was evaluated. Eleven variables, including HIV-1 viral load at diagnosis, Fiebig stage, and CD4 T cell count were evaluated using pairwise correlations, statistical tests, and Cox survival models. Participants had homogeneous demographic and clinical characteristics. Because an antiviral effect was seen in participants who received VRC01 infusion post-ATI, these participants were excluded from the analysis, permitting a pooled analysis of 53 participants. Time to viral rebound was significantly associated with variables measured at the beginning of infection: pre-antiretroviral therapy (ART) viral load (HR = 1.34, p = 0.022), time to viral suppression post-ART initiation (HR = 1.07, p < 0.001), and area under the viral load curve (HR = 1.34, p = 0.026). We show that higher viral loads in acute HIV-1 infection were associated with faster viral rebound, demonstrating that the initial stage of HIV-1 infection before ART initiation has a strong impact on viral rebound post-ATI years later. This work was supported by a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the US Department of the Army (W81XWH-18-2-0040). This research was funded, in part, by the US National Institute of Allergy and Infectious Diseases (AAI20052001) and the I4C Martin Delaney Collaboratory (5UM1AI126603-05).