Biologic aging in people with HIV

Division Of Cancer Epidemiology And Genetics

Investigators

Abstract

Improvements in antiretroviral treatment (ART) for people with HIV (PWH) have resulted in an older population at increasing risk for cancer. Immunosenescence is the biological process of the gradual deterioration of the immune system that occurs with age and has been shown to be accelerated in PWH. There is a need for more research to describe the biological effects of this cellular aging process in PWH in relation to cancer risk. Cancer is a leading cause of death in PWH and is poised to be an increasing cause of morbidity and mortality. Non-Hodgkin lymphoma (NHL) is one of the most common cancers in PWH and has been the leading cause of cancer-attributable death in the US HIV population. While immunosuppression is the major known risk factor for NHL among PWH, other processes such as premature aging may contribute. Numerous molecular markers of biologic aging have been proposed, including epigenetic markers such as the pattern of DNA methylation (DNAm) on CpG sites in peripheral blood mononuclear cells (PBMCs) known as epigenetic clocks. Telomere length (TL) shortens with age as a consequence of cell division and semiconservative replication of DNA at chromosomal ends. Consistent with an acceleration in biological aging during HIV infection, TL in PBMCs is generally shorter in PWH compared to HIV-negative individuals. Biological age as measured by epigenetic clocks is accelerated among PWH compared to chronological age. While the relation between TL and cancer has been studied extensively in the general population and is complex, the association between TL and cancer among PWH has not been assessed. Measures of biological aging from DNAm or TL could help identify individuals at increased risk of NHL and age-related malignancies. We aim to: 1. Evaluate the association of measures of biological aging (DNAm, TL) with NHL risk among PWH. We hypothesize that age acceleration of DNAm and shorter TL will increase NHL risk in PWH, both in unadjusted analyses and after accounting for chronological age. 2. Secondary aim: Evaluate measures of HIV progression in association with accelerated aging among PWH without NHL. We hypothesize that among PWH, lower CD4 count, and detectable HIV viral load will be positively associated with accelerated aging. 3. Secondary aim: Evaluate measures of biological aging in association with clonal hematopoiesis (CH) among PWH without NHL. We hypothesize that measures of biological aging will be positively associated with risk of CH in PWH, both in unadjusted analyses and after accounting for chronological age.