Evidence of greater immune aging among untreated HIV slow progressors than antiretroviral-controlled people living with HIV

BACKGROUND: Uncontrolled HIV viremia results in the progression to AIDS, however, this can be stopped with antiretroviral therapy (ART). Slow progressors are rare individuals who can prevent or delay HIV disease progression without ART. It is unknown whether they experience immune aging akin to normal progressors on ART. METHODS: We investigated persons living with HIV (PWH) who were either HIV slow progressors (n = 58), PWH on ART with undetectable HIV viremia (n = 58), or PWH not on ART with detectable viremia (n = 26), and 56 controls without HIV. The groups were well matched for age and sex. A panel of T-cell differentiation and immune aging markers was measured, along with T and B cell subset telomere length, adjusting for major confounders. RESULTS: Relative to the ART-suppressed HIV group, slow progressors showed immune aging markers indicative of more advanced aging, including lower CD8 naïve:effector memory ratio (standardized effect size -0.41 [95% CI -0.74, -0.07]), and shorter telomere length in B cells (-0.52 [-0.97, -0.07]), CD4 T cells (-0.58 [-0.94, -0.23]), and proliferative CD8 cells (-0.41 [-0.80, -0.01]). Comparison of slow progressors with the control group without HIV showed the same effects. Further, within the slow progressor group, immune aging patterns for the subgroup of elite controllers were not different. CONCLUSIONS: Our findings indicate that despite natural host control of HIV replication, slow progressors show evidence of disproportionately advanced immune aging. This reinforces the potential benefit of ART and emphasizes the need to both diagnose slow progressors and study their potential age-related comorbidities.