Biological ageing with HIV infection: evaluating the geroscience hypothesis

Although people with HIV are living longer, as they age they remain disproportionately burdened with multimorbidity that is exacerbated in resource-poor settings. The geroscience hypothesis postulates that a discrete set of between five and ten hallmarks of biological ageing drive multimorbidity, but these processes have not been systematically examined in the context of people with HIV. We examine four major hallmarks of ageing (macromolecular damage, senescence, inflammation, and stem-cell dysfunction) as gerodrivers in the context of people with HIV. As a counterbalance, we introduce healthy ageing, physiological reserve, intrinsic capacity, and resilience as promoters of geroprotection that counteract gerodrivers. We discuss emerging geroscience-based diagnostic biomarkers and therapeutic strategies, and provide examples based on recent advances in cellular senescence, and other, non-pharmacological approaches. Finally, we present a conceptual model of biological ageing in the general population and in people with HIV that integrates gerodrivers and geroprotectors as modulators of homoeostatic reserves and organ function over the lifecourse.