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HIV and Cardiovascular disease - Contribution of metabolic components and drugs

Signe Westring Worm

Summary

The introduction of combination antiretroviral therapy (cART) in 1996 has dramatically improved the survival of HIV-infected individuals and significantly reduced HIV-related morbidity and mortality. However, this efficient treatment is associated with metabolic side effect and high prevalence of potential CVD risk factors have been reported. The clustering of many of the metabolic side effect associated with the use of cART, has striking similarities to the metabolic syndrome (MS), a term used to describe a clustering of risk factors for cardiovascular disease (CVD). Recent studies have shown an association between exposure to cART and a risk of myocardial infarction (MI), but also HIV per se has a yet not completely understood role for the risk of CVD. 

Based on data from the D:A:D study, the purpose of this thesis was to explore the risk of CVD amongst HIV-infected individuals, in particular by investigating the impact of the metabolic syndrome; by investing the impact of development of DM; and to investigate the risk associated with individual drugs from the NRTI drug class. We found, a strong association between an increasing number of the components of the MS in HIV-infected patients and an increased CVD risk, but the presence of the MS in HIV-infected individuals did not appear to increase the CVD risk above that conferred by the components of the syndrome separately. 

We then compared the impact of development of DM to the impact of pre-existing coronary heart disease (CHD) for the future risk for CHD. We found DM to be an important and independent risk factor for CHD in HIV-infected populations, but it does not appear to confer the same risk as pre-existing CHD. However, it is still of great importance to screen for this modifiable riskfactor and to intervene against the development of DM. 

Thymidine analogues from the NRTI drug class have been associated with the development of insulin resistance, DM and dyslipidemia. Unexpectedly, we found abacavir, a drug with no reported metabolic side effect, significantly associated with an increased risk of myocardial infarction. Further investigations are already initiated to explore the biological explanation for this and aim to in particular to pay attention to the importance of inflammation and CVD in HIVinfected individuals.