Differences in HIV-1 reservoir size, landscape characteristics, and decay dynamics in acute and chronic treated HIV-1 Clade C infection

• DOI: 10.7554/elife.96617.4
• Publication Date: 2025-02-20T11:40:41Z
• Authors: Kavidha Reddy; Guinevere Q Lee; Nicole Reddy; Tatenda JB Chikowore; Kathy Baisley; Krista L Dong; Bruce D Walker; Xu G Yu; Mathias Lichterfeld; Thumbi Ndung'u
• Keywords: Dynamics

Persisting HIV reservoir viruses in resting CD4 T cells and other cellular subsets are a barrier to cure efforts. Early antiretroviral therapy (ART) enables post-treatment viral control some cases, but mechanisms remain unclear. We hypothesised that ART initiated before peak viremia impacts HIV-1 subtype C reservoirs. studied 35 women at high risk of infection from Durban, South Africa, identified with hyperacute by twice-weekly HIV-RNA testing. Participants included 11 starting median 456 (297–1203) days post-onset (DPOV) 24 1 (1–3) DPOV. Peripheral blood mononuclear (PBMCs) were used measured total DNA droplet digital PCR (ddPCR) sequence genomes full-length proviral sequencing (FLIP-seq). during blunted (p<0.0001), contemporaneous did not differ (p=0.104). Over year, decline was observed early treated persons (p=0.0004), late treated. Among 697 genome sequences, the genetic landscape differed between untreated, treated, groups. Intact after year higher untreated (31%) versus (14%) (0%). Treatment both caused more rapid decay intact (13% 51% per month) defective (2% 35%) genomes. However, persisted post chronic treatment undetectable ART. also reduced phylogenetic diversity limited cytotoxic lymphocyte immune escape variants reservoir. Overall, impact seeding associated decay, complexity, escape, which may accelerate clearance combination interventional strategies.