Samir Kumar-Singh

and 17 more

People living with HIV (PLWH) despite having appreciable depletion of CD4 + T-cell show a good SARS-CoV-2 vaccination response. The underlying mechanism(s) are currently not understood. We studied serological and polyfunctional T-cell responses in PLWH receiving anti-retroviral therapy stratified on CD4 + counts as PLWH-high (CD4 ≥500 cells/μL) and PLWH-low (<500 cells/μL). Responses were assessed longitudinally before the first vaccination (T0), 1-month after the first dose (T1), and 3-months (T2), and 6-months (T3) after the second dose. Expectedly, both PLWH-high and -low groups developed similar serological responses after T2, which were also non-significantly different to age and vaccination-matched HIV-negative controls at T3. The IgG titers were also protective showing a good correlation with ACE2-neutralizations (R=0.628, P=0.005). While no difference at T3 was observed between PLWH and controls in activated CD4 +CD154 + and CD4 + memory T-cells, spike-specific CD4 + polyfunctional cytokine expression analysis showed that PLWH preferentially express IL-2 (P<0.001) and controls, IFN-γ (P=0.017). CD4 + T-cell counts negatively correlated with IL-2-expressing CD4 + T-cells including CD4 + memory T-cells (Spearman ρ: ­ -0.85 and -0.80, respectively; P<0.001). Our results suggest that the durable serological and CD4 + T-cell responses developing in vaccinated PLWH are associated with IL-2-mediated CD4 + T-cell activation that likely compensates for CD4 + T-cell depletion in PLWH.