In this study, we investigated the possibility of differential effects of protease inhibitor (PI)-containing (PI+) and PI-sparing (PI−) antiretroviral therapies (ART) on CD8+ T cell apoptosis. We retrospectively analyzed both PD-1 expression and CD8+ T cell apoptosis in a cross-sectional study of HIV-positive adolescents and young adults (mean age = 17.4 years), with perinatally or behaviorally acquired HIV infection. Fifty-one specimens of cryopreserved peripheral blood mononuclear cells (PBMCs) were analyzed using 7-color flow cytometry: 20 from patients receiving PI+ ART, 14 from PI− ART, and 17 from the untreated. The results showed that percentages of PD-1+ CD8+ T cells were strongly correlated with plasma viral loads regardless of treatment (p = 0.0001). The percentage of PD-1+ CD8+ T cells was also positively associated with percentages of Annexin V+ CD8+ T cells (p = 0.04) in the PI+-treated group. The fraction of apoptotic (Annexin V+) CD8+ T cells was associated with viral load in the patients receiving ART that contained one or more protease inhibitors (p = 0.029), but not in the PI− or untreated groups. In summary, we found a direct correlation between PD-1 expression on CD8+ T cells and HIV levels that was not affected by types of medications used in the ART of those adolescents, suggesting that virological success is necessary for PD-1 downregulation. CD8+ T cell apoptosis was linked to high levels of PD-1 expression and HIV viremia. However, there was a higher degree of apoptosis among viremic patients receiving PI therapy, suggesting an immunologically adverse effect of continuing PI+ therapy after virological failure.
