Exceptional T CD4⁺ Recovery Post-antiretroviral Is Linked to a Lower HIV Reservoir with a Specific Immune...

We present a cohort of individuals who reached CD4⁺ T cell counts of greater than 1,000 cells/mm³ (Hypers) after starting antiretroviral treatment (ART) and compared them with 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. Data from individuals living with HIV on their first ART regimen and after 48 months of follow-up were obtained. Immune phenotype by Flow Cytometry analysis on whole blood was performed, cytokines were measured, and integrated HIV-1 DNA was measured by polymerase chain reaction. 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 (Nv) T cells (37.6 vs. 24.8, p < .05), and a low proportion of CD4⁺ effector memory T cells (27.9 vs. 39.4, p < .05), with similar results found in CD8⁺ T cells. Hypers demonstrated a higher percentage of CD4⁺CD45RA⁺CD31^neg cells with a lower response to interleukin-2 stimulation and a lower integrated HIV-1 DNA/CD4 ratio (1.2 vs. 2.89, p < .05). 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 nonthymic-central-Nv cells. This exceptional recovery is associated with a lower HIV reservoir, which may be related to an increase in noninfected CD4⁺ T cells. These patients could then be eligible candidates for cure trials.