Effective antiretroviral therapy (ART) has prolonged life expectancy among people living with HIV (PLWH) in most parts of Europe, but as PLWH are ageing, this group is now starting to experience signs of compromised health, with particular concerns around possible increased rates of frailty, falls and fractures. In this thesis I use data from the Pharmacokinetic and Clinical Observations in People Over Fifty (POPPY) study (699 older (≥50 years) PLWH, 374 younger (< 50 years) PLWH and 304 HIV-negative controls (≥50 years)) to examine some of the challenges of ageing in PLWH in England and Ireland. In particular, I investigate frailty, falls, bone mineral density (BMD), fractures and fracture (hip and major-osteoporotic) risk among PLWH and HIV-negative controls, and examine their associations with demographic, clinical, lifestyle and HIV-specific factors. Results highlight that older PLWH experience increased frailty, a higher prevalence of falls and a greater loss of BMD than younger PLWH and similarly-aged HIV-negative controls. Furthermore, this thesis highlights the importance of demographic characteristics, lifestyle traits, depressive symptoms, physical functioning and HIV-specific factors for the development of frailty, falls and low BMD in PLWH. Among PLWH, I also explore whether the effect of age on the prevalence of frailty could be explained by the effect of HIV parameters by investigating the association of HIV-specific parameters with each of the outcomes considered. Finally, I explore the link between pharmacokinetic (PK) parameters of commonly used nucleoside reverse transcriptase inhibitors (NRTIs) with BMD and with the 10-year probability of fracture. This thesis identified groups at heightened risk for frailty, falls and low BMD, fractures and fracture risk experiencing poor health outcomes against the backdrop of overall improvement of life span among PLWH and aims to inform policy for optimising treatment, tailored to the needs of this population.