UBC Theses and Dissertations
Cardiovascular risk in HIV-positive patients : assessment and pharmacological treatment Johns, Kevin Wesley
In countries where it is available, highly active antiretroviral therapy (HAART) has transformed HIV infection into a manageable, chronic illness rather than an ultimately fatal condition. As HIV/AIDS-related morbidity and mortality have declined, adverse metabolic effects risen in frequency due to the combined effects of HAART and HIV infection itself. Adverse effects include blood lipid elevations that, in turn, lead to increased cardiovascular risk, potentially resulting in cardiovascular disease (CVD) or death. Treatment and management of these metabolic effects is becoming paramount within the HIV-positive (HIV+) population to extend the lifespan and improve quality of life. A variety of studies were employed in order to accurately gauge both the risk of CVD posed to the HIV+ population and the efficacy of novel and accepted treatments for metabolic abnormalities in this population. A longitudinal cohort study served to assess the incidence of important metabolic endpoints in HAART-naïve patients initiating therapy. A cross-sectional study was used to assess the prevalence of peripheral arterial disease (PAD), a largely unexplored but clinically relevant cardiovascular endpoint. Two clinical trials investigated the efficacy of treatment in HIV+ patients with elevated cardiovascular risk. One explored the effect of the anti-hyperglycemic agent rosiglitazone on carotid intima media thickness and total plaque area. The second compared the effectiveness of two treatment strategies in patients not reaching lipid targets with rosuvastatin 10 mg: increasing the dose to 20 mg or adding ezetimibe 10 mg to ongoing rosuvastatin. Findings of the cohort study included a unique and unexpected pattern of treatment-associated lipid abnormalities in HIV+ patients initiating therapy with non-nucleoside reverse transcriptase inhibitors. A low prevalence of PAD was observed in our population of HIV+ subjects most likely secondary to the young age of the participants and factors that confounded the method of assessment. Rosiglitazone did not prove to be an effective agent at reducing surrogate markers for CVD but did have positive effects on endothelial function and inflammatory markers. Finally, the addition of ezetimibe to ongoing rosuvastatin therapy was effective at lowering relevant endpoints, including apolipoprotein B, but did not perform significantly better than a doubled dose of rosuvastatin.
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