Challenges of Statins in HIV Hyperlipidemia

As a result of advanced medication regimens, particularly protease inhibitors (PIs), the life expectancy of HIV-infected adults has risen considerably. As a result, non-AIDS comorbidities of chronic illness, such as cardiovascular disease (CVD), non-AIDS cancer, and liver disease, now account for the majority of deaths. While traditional risk factors such as age, smoking, diabetes, and dyslipidemia influence the development of CVD in HIV-infected individuals, infection with HIV may be considered an independent risk factor for CVD. The risk for CVD is elevated in HIV-infected individuals even when traditional risk factors are taken into account: a cohort study found a significant difference in rates of acute myocardial infarction between HIV and non-HIV infected adults, with a relative risk (RR) of 1.75 (95 % confidence interval [CI] 1.51–2.02; p<0.0001), adjusting for age, gender, race, hypertension, diabetes, and dyslipidemia. Furthermore, traditional calculators of risk for CVD may significantly underestimate the likelihood of CV events in HIV-infected individuals, By 2015, approximately 50 % of adults infected with HIV will be over the age of 50, thus adding another risk factor for CVD. CVD has become one of the most common causes of mortality in HIV-positive individuals in resource-rich countries. The risk for CVD in HIV is increased through numerous mechanisms that affect the atherosclerotic process. HIV infection itself causes a state of chronic inflammation that promotes atherosclerosis via immune activation. Concomitant infections such as cytomegalovirus (CMV) may also promote atherosclerosis. Furthermore, rates of smoking are high among HIV-infected individuals compared with the general population. Other traditional risk factors such as insulin resistance, hypertension, and hyperlipidemia are major contributors to the excess CVD risk observed in HIV-infected patients. There is evidence that traditional risk factors contribute to the formation of calcified plaque, while immune activation and other non-traditional risk factors are associated with non-calcified plaque, which may be more prone to rupture. Clinical data suggest that the observed lipid abnormalities among people with HIV may be the result of the viral infection, and its induced cytokine dysregulation, antiretroviral therapy (ART), or, most likely, both. Hyperlipidemia is now a common clinical feature of ART-treated patients and has therefore become an important therapeutic target to reduce CVD risk in these patients. Abstract As a result of access to potent antiretroviral therapy (ART), HIV-infected adults with virologic suppression are living longer, but unfortunately are at increased risk for developing comorbid conditions. It is postulated that this increased risk seen at all ages is partly due to the effects of viral-mediated chronic inflammation in addition to the traditional risk factors. One of the more common traditional risk factors, hyperlipidemia, may be worsened by ART. However, the benefits of ART greatly outweigh the possible negative effects of ART agents on lipid parameters. As the HIV-infected patient population ages, it is critical to control hyperlipidemia in ART-treated patients in order to reduce the risk for long-term cardiovascular complications. If hyperlipidemia cannot be managed through lifestyle modifications, clinical guidelines recommend the use of lipid-lowering medication, particularly HMG Co-A reductase inhibitors (statins), to reduce low-density lipoproteins-cholesterol. However, many ART agents inhibit or induce major metabolic pathways of statins, creating potentially serious drug–drug interactions. In this article, we present a review of the various challenges in managing hyperlipidemia with a focus on drug–drug interactions.