T-Cell Subset Distribution in HIV-1–Infected Patients After 12 Years of Treatment-Induced Viremic Suppression

OBJECTIVE: Residual immune activation and skewed T cell maturation may contribute to excess comorbidity and mortality in successfully treated HIV-infected patients, and long-term effects of combination antiretroviral therapy (cART) on immune reconstitution remain a debated issue. Quantitative T cell reconstitution and activation and its association with residual viremia in patients with 12 years of viremic suppression were investigated. DESIGN: Blood samples collected cross-sectionally from 71 HIV-infected patients with cART-induced viremic suppression through 12 years were compared with samples from 16 healthy controls. METHODS: Several different subsets of naive, memory, and activated T cells were analyzed in fresh whole blood by 6-color flowcytometry, and ultrasensitive quantification of HIV RNA was performed. RESULTS: HIV-infected patients had lower absolute and relative CD4 T cell counts and higher absolute and relative CD8 T cell counts than controls. HIV-infected patients had lower concentrations of naive CD4 cells than controls, but proportions were similar. HIV-infected patients had higher concentrations of CD8 T cells than controls in all the examined subsets but only a higher proportion of CD8 cells in the intermediately differentiated and activated subsets. Residual viremia did not correlate to proportions of naive CD4, CD4 recent thymic emigrants, or activated CD8 T cells. CONCLUSIONS: This study demonstrated some degree of T cell imbalance even after 12 years of successful cART. Large longitudinal studies are needed to establish whether these discrete changes have clinical relevance.