Composition and Function of T Cell Subpopulations Are Slow to Change Despite Effective Antiretroviral Treatment of HIV Disease. PLoS One 9: e85613

The ability to reconstitute a normal immune system with antiretroviral therapy in the setting of HIV infection remains uncertain. This study aimed to characterize quantitative and qualitative aspects of various T cell subpopulations that do not improve despite effective ART. CD4:CD8 ratio was evaluated in HIV-infected subjects with viral loads.10,000 copies/ml (‘‘non-controllers’’, n = 42), those with undetectable viral loads on ART (‘‘ART-suppressed’’, n = 53), and HIV-uninfected subjects (n = 22). In addition, T cell phenotype and function were examined in 25 non-controllers, 18 ART-suppressed, and 7 HIV-uninfected subjects. CD4:CD8 ratio in non-controllers, ART-suppressed, and HIV-uninfected subjects was 0.25, 0.48, and 1.95 respectively (P,0.0001 for all comparisons). The increased ratio in ART-suppressed compared to non-controllers was driven by an increase of CD4+ T cells, with no change in the expanded CD8+ T cell population. Expansion of differentiated (CD282CD272CD45RA+/2CCR72) T cell subpopulations persisted despite ART and minimal changes were noted in naı̈ve T cell frequencies over time. Increased number of CD8+CD282 T cells and increased CD8+ CMV-specific T cell responses were associated with a decreased CD4:CD8 ratio. Measures of T cell function demonstrated persistence of high frequencies of CD8+ T cells producing IFN–c. Lastly, though all CD8+ subpopulations demonstrated significantly lower Ki67 expression in ART-suppressed subjects, CD4+ T cell subpopulations did not consistently show this decrease, thus demonstrating differen