Changes in Causes of Death, the Impact on Life Expectancy, and the Risk of Myocardial Infarction Among People Living with and without HIV

Background: Within the context of aging with HIV in the combination antiretroviral therapy (ART) era, the set of four papers that make up this dissertation aimed to: summarize the existing evidence on the risk of myocardial infarction (MI) among people living HIV (PLHIV) (Chapter 2); characterize changes over time in rates and causes of death among HIV-positive and HIV-negative individuals (Chapter 3); assess the impact of the changing causes of death on life expectancy and potential gains in life expectancy over time (Chapter 4); estimate the incidence of MI and its association with HIV infection, ART, and other explanatory variables, among HIV-positive and HIV-negative individuals (Chapter 5).Methods: A systematic review and meta-analysis of MI risk among PLHIV was initially performed. Next, data from the COAST studya linked population-based, retrospective cohort study containing longitudinal data on over half a million HIV-positive and HIV-negative adults in British Columbia (BC)were assessed to investigate several issues pertinent to aging with HIV. With the hope of producing evidence to inform relevant programmatic and clinical guidelines/policies among aging HIV-positive individuals, a series of analyses were performed to examine mortality changes over time, cause-deleted life expectancy, and the risk of MI among HIV-positive compared to HIV-negative individuals. Results: We observed significant declines in mortality and dramatic shifts in the causes of death between 1996 and 2012 among HIV-positive compared to HIV-negative individuals. Although HIV/AIDS continues to account for the greatest burden of mortality among PLHIV, other non-AIDS-defining conditions have become increasingly relevant. Consequently, our results suggest that managing cardiovascular diseases and non-AIDS-defining cancers among PLHIV has the same effect on life expectancy in this population as in HIV-negative individuals. Increasing age, male sex, and HIV infection (including exposure to some ART regimens) were found to be associated with a higher risk of MI.Conclusion: Taken together, our findings highlight the increasing need to concurrently consider multiple factors, including HIV infection itself, other emerging non-HIV-related conditions, exposure to ART, and demographic and clinical risk factors, as part of the effort to address and improve the care of aging HIV-positive individuals.