Exploring Potential Associations Between HIV Acquisition and Biological Aging: Insights from a Bidirectional...

Accumulating evidence indicates that HIV acquisition may be associated with premature aging. However, the causal relationship and the direction of the effect between HIV acquisition and aging remain controversial. In the present study, we aimed to investigate the causal associations between HIV acquisition and biological aging. Summary data for biological aging proxy and HIV acquisition were collected from the most updated and available genome-wide association studies. Biological aging proxied by telomere length (TL) and four epigenetic clocks, including intrinsic epigenetic age acceleration, GrimAge acceleration, HannumAge acceleration, and PhenoAge acceleration. Four Mendelian randomization (MR) methods, including inverse-variance weighted (IVW), weighted median, MR-Egger, and weighted mode, were used to assess causal associations. Multiple sensitivity analyses, including heterogeneity analysis, leave-one-out sensitivity analysis, and horizontal pleiotropy analysis, were further performed to verify the robustness of our findings. The IVW MR results indicated that genetically predicted HIV acquisition was not significantly associated with biological aging (all p > .05). Similarly, the reverse-direction MR also did not identify potentially causal effects of biological aging on HIV acquisition (all p > .05). This study found no obvious evidence of the causal relationship between HIV acquisition and biological aging. More studies are needed to future unravel the potential causal relationship and the exact mechanism.