Distinct features of immune activation and exhaustion markers in people with perinatally-acquired HIV

Objective: The aim of this study was to characterize T cell activation, exhaustion, maturation and Treg frequencies in individuals who acquire perinatal HIV (PHIV), in individuals who acquired HIV as adult (AHIV), and in healthy controls (HC). Design: This cross-sectional study included people with HIV ≥ 14 and <40 years, HIV-RNA < 50 copies/mL on antiretroviral therapy for at least 6 months, and HC. Methods: We assessed the expression of PD-1, TIM-3, EOMES, CD38+ DR+, maturation status by CD4+ and CD8+T cells and the frequency of CD4+ and CD8+ Treg cells. Principal component analysis (PCA) and k-means cluster analysis investigated which combination of immunological parameters better associated with each group. Results: 26 PHIV and 18 AHIV with median ages of 26 (8.0) and 28 (6.8) years were consecutively enrolled. PHIV showed significant higher frequency of naïve and lower frequency of terminal effector memory CD4+ and CD8+ T cells than AHIV. AHIV exhibited higher expression of exhaustion and activation markers. The statistical analysis returned two clusters with 94% of specificity and 88% of sensitivity identifying PHIV vs. AHIV. The 9 HC had a lower expression of exhaustion markers on both CD4+ and CD8+T lymphocytes than PHIV and AHIV. Conclusions: These data may exclude major alterations of lymphopoiesis in PHIV, with even lower state of immune-activation and exhaustion compared with AHIV. This suggests that recent lack of virological control, may affect immune activation and exhaustion of CD4+ and CD8+ T cells.