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Abstract
In the absence of a cure, the management, treatment, and monitoring of HIV disease is likely to be life long. As HIV treatment strategies move towards initiating therapy earlier, the number of HIV-positive persons receiving antiretroviral therapy (ART) is anticipated to increase. While the shorter-term response to ART has been studied extensively, fewer studies have evaluated longer-term responses to ART. This work aims to inform the expected experience of initiating ART, risk of modifying treatment, and longer-term immunological and virological response through up to 13 years of treatment.
In Australia, rates of ART initiation from time of first positive HIV diagnosis were previously unknown. When to initiate treatment strategies have evolved over time and this research highlights the so-called treatment pendulum, including establishing a set of benchmark ART initiation rates by treatment era. Optimal HIV treatment requires the maintenance of a durable antiretroviral regimen affording full virological suppression. Barriers to optimal treatment adherence might be addressed through minor or major modifications to the initial ART regimen. Demonstrated here and focusing on major ART modifications, Australian data are compared with resource-rich and resource-limited data from the Asia-Pacific region. Rates of major modification primarily occur on resource availability and by varying levels of treatment toxicity or at the patients/physicians discretion.
HIV-positive populations are ageing due to survival from effective ART. However, the cumulative effects of persistent low-grade chronic immune activation, ART-induced pro- inflammation, and episodic viraemia exposure are largely unknown. Studying the longer-term immunological response to continual suppressive therapy showed that following the plateau response phase (typically 3-5 years of ART), minimal changes in CD4 cell counts are observed through a further 5-13 years of treatment. Importantly, older patients showed little signs of diminishing immune function as expressed in CD4 cell counts. Using a novel measure of cumulative viraemic burden after initiating ART, results in this thesis demonstrate a higher cumulative viral burden is associated with increased risk of all-cause mortality. Furthermore, predictors of patients susceptible to higher cumulative viraemia after initiating ART can be identified using routinely collected clinical information.