Acute HIV Infection and ART Response: Insights into T Cell Subsets, Activation, Exhaustion, and Blood and GALT HIV Reservoir

Investigating immunological and viral reservoir dynamics in blood and GALT during acute HIV phase advances understanding of HIV persistence. Dynamics of T cells and HIV reservoirs immediately after early ART require further investigation. We evaluated the ART impact at 12 (M12) and 24 months (M24) on immunological, virological and reservoir markers of 24 participants starting ART at Fiebig ≤ V (Baseline = D0) in a Brazilian cohort. We measured the frequency of T cell activation, exhaustion, memory subsets, Th17 and pTfh cells by flow cytometry and quantified total HIV DNA by qPCR in PBMC and GALT. Most participants were cisgender MSM (95.9%), with a median age of 27 years (IQR 25-36). At enrollment (D0), four participants used triple ART as PEP, and two were under oral PrEP and they exhibited higher CD4/CD8 ratios. Higher CD4/CD8 ratios were also observed in participants classified as Fiebig I to III. A total of 92% achieved viral suppression at M12 and 96% at M24. CD4 counts rose from 646 to 861 cells/mm³, and the CD4/CD8 ratio improved from 0.76 to 1.24 (<i>p</i> < 0.01). HIV DNA in PBMCs decreased 4-fold by M12 and 61-fold by M24, with 50% of participants reaching undetectable levels by M24 (<i>p</i> < 0.01). In GALT, undetectable HIV DNA increased from 27% at D0 to 75% at M12. HIV DNA in PBMCs and GALT correlated with plasma VL, while the CD4/CD8 ratio was inversely linked to PBMC reservoirs (rho = -0.66; <i>p</i> < 0.05). Early ART reduced activated CD8⁺ T cells (<i>p</i> < 0.05) but had minimal effects on CD4⁺ T cells or exhaustion markers. By M24, CD8⁺ TCM increased, and CD8⁺ TEF decreased (<i>p</i> < 0.01), while Th17 and pTfh levels remained stable. Early ART led to viral suppression and immune restoration, and influenced reservoir dynamics. The CD4/CD8 ratio was shown to be a key marker of early treatment success. Since a quarter of the participants were identified while initiating PrEP/PEP, it is important to consider the acute phase window according to vulnerability. Recent PEP/PrEP use often excludes participants from clinical trials on bNAbs and therapeutic vaccines targeting viral reservoirs during the acute phase of HIV. Since these are the populations that may benefit from these strategies, larger studies including those people are needed.