HIV-1 Reservoir Size and Diversity Among Acute-Infected Individuals

Early combined antiretroviral treatment (cART) of HIV infection aims to limit the seeding of the viral reservoir in the initial phase of infection, and, consequently, decrease the intrahost viral diversity. Here, we aimed to measure the effect of the cART in the size and complexity of the proviral reservoir. Peripheral blood mononuclear cell (PBMC) and plasma samples were obtained from ten HIV-infected individuals, diagnosed at the acute phase (Fiebig II-V) of infection, before (PreART) and 12 months (M12ART) after suppressive cART. HIV proviral reservoir size was determined by quantitative real time PCR while the intrahost viral diversity of the env C2-V3 region was assessed by single genome amplification or next-generation sequencing in PBMC and plasma, respectively. The mean nucleotide diversity (π) and the normalized Shannon entropy (HSN) were used to infer the complexity of the viral population. Overall, we identified the immunological recovery of patients, with CD4+ T cell gain of 31% (P=0.008) and a normalization of the CD4/CD8 ratios (~1.0, P=0.016) after 12 months under cART. We also observed significant decreases in the HIV-1 RNA (~4 log, P=0.004) and DNA (~1 log, P=0.002) levels. The median time to achieve viral suppression was three months. The high intermixing between the sequences from both visits suggests that the HIV-1 DNA reservoir remained remarkably stable under the cART. There was a slightly reduction in proviral π (PreART=0.20 vs M12ART=0.10; P=0.156) and a significant decrease in HSN (PreART=0.41 vs M12ART=0.25; P=0.019) after one year of cART. We found no correlation between π or HSN at PreART with the rate of HIV DNA decay, T CD4+ cell change or CD4/CD8 ratios presented at M12ART. One year of cART initiated in acute phase was sufficient to reduce the size and complexity of proviral reservoir, and to achieve immunological restoration, independently of the HIV-1 plasmatic viral load, CD4+ T cells count or HIV-1 subtype. The early initiation of cART may favor strategies to achieve post-treatment control of HIV and, ultimately, a functional cure, through the restriction of the pool of variants, allowing a more focused targeting by therapeutic vaccines or other immune approaches