Effective antiretroviral therapy (ART) prevents AIDS-related disease and death and has transformed HIV from an invariably fatal disease to a long-term chronic condition. This phenomenal success has resulted in the overall life expectancy of people with HIV (PWH) approaching that of the general population, however, the disease-free life expectancy of PWH remains 16 years lower. This is largely due to an increased risk of age-related, non-communicable diseases including neurocognitive decline, frailty, bone disease, metabolic conditions and cardiovascular disease (CVD) in PWH. CVD is one of the leading causes of death of PWH on ART, with the global burden tripling in the past 20 years. PWH are approximately twice as likely to have a cardiovascular event as those without HIV and this effect is independent of traditional risk factors such as smoking and cholesterol. The factors driving increased chronic disease risk in PWH remain incompletely defined but are hypothesised to include persistent inflammation and immune dysfunction, gut barrier disruption and viral persistence/reactivation. A thorough understanding of the relevant mechanistic pathways is required to inform how we prevent and treat these conditions in PWH.
We have characterised the long-term impact of HIV on innate immune cells including monocytes/macrophages and NK cells and found HIV induces substantial changes to their phenotype and function which are not fully reversed by suppressive ART. The involvement of monocytes in atherosclerosis (which underlies most cardiovascular diseases) is a particular focus of our work and we have shown HIV is associated with ‘pro-atherogenic’ changes to monocytes which may contribute to heightened atherosclerosis in vivo. Ongoing work includes characterising what is causing these pro-atherogenic changes in PWH and identifying how they can be mitigated, as well as identifying predictive biomarkers of cardiovascular events in PWH which can be used clinically to help prevent disease in this population.