BACKGROUND:We reported T-cell senescence to be similar in people living with HIV (PWH) with suppressed viremia (predominantly men who have sex with men (MSM)) and HIV-negative otherwise comparable controls, but greater than in healthy blood donors. This lead us to compare CD4+ and CD8+ T-cell counts and CD4+/CD8+ ratios between HIV-negative MSM and men who only have sex with women (MSW), and relate observed differences to behavioral factors and infectious exposures, including cytomegalovirus (CMV) infection. METHODS:In 368 HIV-negative MSM and 72 HIV-negative MSW T-lymphocyte phenotyping was performed 3 times biennially. Baseline CMV serology, and STI-incidence/-seroprevalence, sexual and substance-use behavior data were collected during study visits. RESULTS:MSM, compared to MSW, had higher CD8+ counts (551 vs. 437 cells/mm3, P<.001), similar CD4+ counts (864 vs. 880 cells/mm3, P=.5) and lower CD4+/CD8+ ratios (1.84 vs. 2.47, P<.001). Differences were most pronounced for MSM with >10 recent sex partners, and partly explained by higher CMV seroprevalence in MSM. DISCUSSION:These findings suggest that factors other than HIV may, both in PWH and certain HIV-negative MSM, contribute to a low CD4+/CD8+ ratio. Whether this, like in PWH, contributes to comorbidity risk in HIV-negative MSM requires further study.