Accelerated Immune Senescence and Biological Aging of T-cell Subsets Among ART-naive HIV-infected Men Who Have Sex With Men in Beijing, China: a Case-control Study

Abstract Background: The average lifespan of HIV-infected subjects remains shorter compared to uninfected individuals. Accelerated senescence may be responsible for this difference despite effective antiretroviral therapy (ART) with successful viral suppression. The present study aimed to assess the impact of HIV on immune and biological senescence of ART-naive HIV-infected men who have sex with men (MSM) in Beijing, China. Methods: A cross-sectional study was conducted that compared MSM HIV-infected patients and age-matched MSM HIV negative controls. Within the CD4 and CD8 population, the percentages of naive(TN), central memory(TCM), effector memory(TEM) and terminally differentiated memory(TemRA) subsets were studied and markers of senescence and activation in these cells were measured by multiparameter flow cytometry. Naive (CD45RA+) and memory (CD45RO+) CD8 T cells were purified by MACS technology. Telomere length was quantified by real-time PCR. Results: Within the CD8 T cell subsets, TN, TCM,TEM and TemRA cells showed more activation (HLA-DR+) and replicative senescence(CD28-CD57+) phenotypes in ART-naive MSM. However, in the CD4 T cell subsets, expect for TN, the percentage of senescent cells did not differ between ART-naive MSM and uninfected controls, but activated cells were upregulated in the former. The telomere length of naive and memory CD8 T cells was significantly shorter in ART-naive MSM than that of uninfected controls.Conclusion: Our results indicate that HIV-infected ART-naive MSM exhibit accelerated immune senescence with premature biological aging, which particularly affects the CD8 T-cell subsets. This highlights the strong impact of HIV on aging process of T-cell despite patient’s young age at infection and supports the importance of early control of HIV replication.