De Francesco, Davide; (2020) Assessing comorbidity burden, ageing and cognitive impairment of people living with HIV. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The widespread use of effective combination antiretroviral therapy and the consequent increase in the longevity of people living with HIV (PLWH) have raised questions relating to the ageing and development of comorbidities in PLWH. In this thesis, I analysed data from observational cohort studies of PLWH to investigate different aspects concerning the operationalisation of comorbidity burden, ageing and cognitive impairment. Using data-reduction techniques, I have combined comorbidity data to explore patterns of comorbidities and develop an index measuring the overall comorbidity burden, specifically in PLWH. Patterns of mental health problems, cardiovascular and sexually transmitted diseases were frequent in PLWH, had different risk factors and differential impacts on quality of life and healthcare resource use. My proposed comorbidity index exhibited good construct and content validity, showing strong associations with quality of life related to both physical and mental health, as well as with other age-related outcomes, even when evaluated in an independent validation cohort. When assessing the overall ageing process using a panel of biomarkers, PLWH and HIV-negative individuals with similar lifestyles appeared, on average, 13 and 5.5 years older, respectively, than their actual chronological age. However, PLWH appeared significantly older than HIV-negative controls (p<0.001) and the difference did not appear to be explained by other coinfections (hepatitis B and cytomegalovirus) or HIV-related parameters (prior immunosuppression and exposure to saquinavir), that were also associated with age advancement. There was poor agreement between three commonly used definitions of cognitive impairment, and each definition was also poorly associated with subjectively-assessed cognitive complaints and other patient-reported outcomes. However, by using a combination of two of these three definitions, I was able to identify PLWH with poorer cognitive performance and a higher rate of complaints with reasonable accuracy. Finally, different sets of biomarkers appeared to be differently associated with age-related outcomes with, for example, T cell phenotyping markers and N-glycans showing a major role in predicting comorbidity burden. In conclusion, these findings provide new insights into different aspects related to the ageing of PLWH, which could inform and improve the care of the increasing number of PLWH with multi-morbidity and at risk of developing age-associated comorbidities, including cognitive disorders.

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