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.96617.2
• Publication Date: 2024-10-11T18:25:07Z
• 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 the main barrier to cure efforts. Antiretroviral therapy (ART) intensification by early initiation has been shown enable post-treatment viral control some cases but underlying mechanisms not fully understood. We hypothesized that ART initiated during hyperacute phase of infection before peak will affect size, decay dynamics landscape characteristics HIV-1 subtype C reservoirs.We studied 35 women at high risk from Durban, South Africa identified with twice weekly testing for plasma RNA. Study participants included 11 who started a median 456 (297-1203) days post onset viremia (DPOV), 24 1 (1-3) DPOV. used peripheral blood mononuclear (PBMC) measure total DNA ddPCR sequence genomes full length individual proviral sequencing (FLIP-seq) detection up year treatment initiation.Whereas blunted compared untreated individuals (p<0.0001), there was no difference measured contemporaneously (p=0.104). There steady decline treated persons over (p=0.0004), significant change observed late group. Total after one lower group (p=0.02). Generation 697 single genome sequences revealed longitudinal genetic between untreated, treated, infection: relative contribution intact pool higher (31%) (14%) (0%). Treatment both resulted more rapid (13% 51% per month) versus defective (2% 35% genomes. However, were still chronic contrast where longer detectable. Moreover, reduced phylogenetic diversity limited seeding persistence cytotoxic lymphocyte immune escape variants reservoir.Overall, our results show whereas did impact seeding, it nevertheless associated genomes, decreased complexity reservoirs, which could accelerate clearance when combined interventional strategies.