Exceptional T CD4+ recovery post-ART is linked to a lower HIV reservoir with a specific immune differentiation pattern.

- Objective: We present a cohort of individuals who reached CD4+ T-cell counts of greater than 1000 cells/mm3 (Hypers) after starting antiretroviral treatment (ART) and compared them to those who reached between 350 and 999 CD4+ T-cells/mm3 (Concordants). Demographic data, immune recovery kinetics, T CD4+ subset phenotypes and integrated HIV DNA were analyzed. - Design and Methods: Data from individuals living with HIV on their first ART regimen and after 48 months of follow-up was obtained. Immune phenotype by Flow Cytometry analysis on whole blood was performed, cytokines were measured, and integrated HIV-1 DNA was measured by PCR. - Results: From a total of 424 individuals, 26 Hypers (6.1%), 314 Concordants (74.1%) and 84 (19.8%) discordants were identified. Hypers had a higher proportion of CD4+naive T-cells (37.6 vs 24.8, p< 0.05), and a low proportion of CD4+EM T-cells (27.9 vs 39.4, p< 0.05), with similar results found in CD8+ T-cells. Hypers demonstrated a higher percentage of CD4+CD45RA+CD31neg cells with a lower response to IL-2 stimulation and a lower intergrated HIV-1 DNA/CD4 ratio (1.2 vs 2.89, p<0.05). - Conclusions: In Hypers, T-cell recovery occurs very early after initiation of ART. Following this initial recovery state, their CD4+ T-cell level homeostasis seems to be driven by non-thymic-central-naive cells. This exceptional recovery is associated with a lower HIV reservoir which may be related to an increase in non-infected CD4+ T cells. These patients could then be eligible candidates for cure trials.