Ageing with HIV: From pathogenesis to policy

People living with HIV (PLWH) increasingly become older, reflecting the benefit of antiretroviral treatment. Naturally, PLWH are increasingly suffering from ageing-associated comorbidities, the risk of which however is even higher than in HIV-negative individuals. This thesis aimed to contribute to our understanding of what drives comorbidity burden in PLWH and our ability to mitigate comorbidity burden and optimize health care in PLWH, particularly focusing on cardiovascular disease and cognitive impairment. We have shown that the pathogenesis is multifactorial and involves both traditional and HIV-related risk factors. Traditional risk factors include smoking, hypertension, and dyslipidaemia and may have a larger role than previously perceived. Furthermore, persistent inflammation and immune activation despite antiretroviral treatment may contribute to the development of comorbidities. Lastly, PLWH with a particular clinical history or phenotype may be more vulnerable to comorbidities, notably those who have experienced prolonged periods of untreated HIV infection, HIV-related immunodeficiency and/or severe prior HIV disease, and those who have been exposed to more toxic antiretroviral drugs. Interventions targeting PLWH at high risk of developing comorbidities could avert the majority of events. Whereas we have shown that several risk prediction algorithms are suitable for use in clinical practice to identify PLWH at high risk of developing cardiovascular disease, this was not the case for various screening instruments for HIV-associated cognitive impairment. In summary, prioritizing interventions focusing on traditional risk factors and early antiretroviral treatment initiation are expected to best mitigate comorbidity burden and contribute to maintaining long-term health in PLWH as they age