part of 10.2217/17460875.3.2.175 © 2008 Future Medicine Ltd ISSN 1746-0875 REVIEW Future Lipidol. (2008) 3(2), 175–188 175 Current and future treatments of HIV-associated dyslipidemia MT Bennett, KW Johns & GP Bondy † † Author for correspondence University of British Columbia, Department of Medicine, Vancouver, Canada, and, Immunodeficiency Clinic- HIV Metabolic Clinic, St Paul’s Hospital, Vancouver, Canada Tel.: +1 604 806 8591; Fax: +1604 806 8590; gbondy@ providencehealth.bc.ca Keywords: anticholesteremic agents, antiretroviral agents, cholesterol, HIV infections, hyperlipidemias The dyslipidemia associated with HIV is common and is attributed to HIV itself and/or the antiretroviral therapy used to treat HIV. The treatment of this dyslipidemia includes lifestyle changes, such as diet and exercise, altering the antiretroviral therapy and lipid-lowering therapy. The current guidelines suggest the use of a statin for elevations in LDL. For elevations in triglycerides, a fibrate followed by fish oil/niacin is suggested as first and second-line therapy. We anticipate that the updated guidelines will suggest the use of rosuvastatin for high LDL and ezetimibe as a therapeutic option in patients not reaching LDL goals or who are intolerant of statins. It is estimated that 33.2 million people are infected with HIV worldwide [1]. With the advances in antiretroviral therapy the prognosis of patients infected with HIV is improving. With this increase in survival there is an associated increase in the prevalence of cardiovascular disease and its complications within this group. Although the reason for this appears to be multifactorial, a pro- portion of the attributable risk is likely secondary to the dyslipidemia associated with HIV. The dyslipidemia associated with HIV can be caused by both HIV itself and its treatment. The dyslipidemia caused by HIV itself is character- ized by elevations in serum triglycerides, VLDL and LDL, and reductions in HDL and total cho- lesterol [2–6]. The proposed mechanisms of this dyslipidemia include anomalous hepatic metab- olism in the form of accelerated lipogenesis [4], decreased clearance of triglyceride-rich lipopro- teins and metabolic alterations mediated by cytokines, namely interferon-α [6]. Antiretroviral therapy & its affect on the lipid profile In the current era of HIV treatment most patients who have access to antiretroviral (ARV) therapy will be treated with it at some point over the course of their disease. Although these treat- ments are lifesaving and markedly prolong sur- vival, ARV adversely affects the lipid profile. Each class of ARV (protease inhibitors [PIs], nucleoside reverse transcriptase inhibitors [NRTIs], non-nucleoside reverse transcriptase inhibitors [NNRTIs] and fusion inhibitors) have different effects on the lipid profile. In the absence of prospective, randomized, placebo- controlled trials it is difficult, however, to assess the specific effects of individual ARVs on the lipid profile. Protease inhibitors A number of PIs can induce a characteristic dys- lipidemia: hypertriglyceridemia, an increase in total cholesterol and LDL and in certain individu- als a low HDL (Tables 1 & 2) [7–18]. There is a wide variation in the frequency of dyslipidemias induced by PIs. The PI that is associated with the highest frequency of dyslipidemias is ritonavir. Ritonavir is commonly used in PI-based ARVs regimens [19]. Ritonavir is a potent inhibitor of cytochrome P450 3A4 (CYP3A4) and is used to increase or ‘boost’ the circulating blood levels of PIs co-administered with ritonavir. Purnell et al. showed that ritonavir induces this characteristic dyslipidemia in HIV-negative individuals [11]. These effects appear to be dose dependent. Shafran et al. demonstrated that although ritonavir still adversely affected the lipid profile when administered at a low dose, these effects were less severe when tested in HIV-negative individuals [20]. Other PIs show varying effects on lipids. Atazanavir does not cause significant changes in lipid levels when administered in mono- therapy [21]. The use of atazanavir monotherapy, however, is currently not recommended for the treatment of HIV [19]. When atazanavir is co-administered with ritonavir in boosted regimes it can induce dyslipidemias [22]. Since most PIs are administered in boosted regimes with ritonavir, it can be difficult to assess the effect of an individual PI with regards to the induction of a dyslipidemia. A limited number of studies have analyzed the effects of specific PIs against one another. Johnson et al. [23] compared atazanavir and lopinavir in ritonavir-boosted regimes in treat- ment-experienced patients. The lopina- vir/ritonavir regime caused significant increase in total cholesterol (+9%) and triglycerides (+30%) compared with atazanavir/ritonavir. For reprint orders, please contact: reprints@futuremedicine.com