Protease Inhibitor-Induced Hyperlipidemia Treated With Pioglitazone

Patients infected with human immunodeficiency virus (HIV) have been found to be prone to lipid abnormalities because of specific antiretroviral therapy (ART) and HIV infection itself and thus may be more susceptible to coronary artery disease. Antiretroviral drugs associated with the development of dyslipidemia in these patients include protease inhibitors and nucleotide reverse transcriptase inhibitors. Management of ART-associated hyperlipidemia may pose some challenges because of the increased risk of complications with the use of medications, particularly 3-hydroxy-3methyl-glutaryl-CoA reductase inhibitors and fibric acid derivatives that may interact with various ART drugs. Because of the proven antihyperlipidemic effects of pioglitazone, a thiazolidinedione, in patients with type 2 diabetes mellitus and the lack of adverse effects, it may be used effectively in the treatment of ART-induced hyperlipidemia. We present a case of a 49-year-old man infected with HIV whose protease inhibitor–induced hyperlipidemia improved with the administration of high-dose pioglitazone. (Infect Dis Clin Pract 2008;16:131–133) Hyperlipidemia with increased total and low-density lipoprotein (LDL) cholesterol has been associated with coronary heart disease in the general population. In human immunodeficiency virus (HIV)–infected individuals who are undergoing antiretroviral therapy (ART), lipid elevations have been reported at higher frequencies compared with the general population. It has been reported that in the first 4 to 6 years of highly active antiretroviral therapy (HAART), there is a 25% increase likelihood of coronary artery disease. Although it remains uncertain whether such metabolic changes can actually accelerate cardiovascular disease and how this might occur, physicians treating HIV-infected patients are nevertheless interested at lowering any potential cardiovascular risks in this patient population. It is becoming increasingly evident that certain antiretroviral therapies can be associated with specific lipid alterations, most commonly, hypertriglyceridemia. Several studies have shown that the rate of hyperlipidemia can be high especially in patients treated with protease inhibitor (PI)– based regimens. Nucleoside reverse transcriptase inhibitors have also been proposed as a potential risk factor in the development of lipid abnormalities in HIV patients. However, current evidence suggests that it is overly simplistic to attribute ‘‘cause’’ exclusively to any single ART class and to assume that all changes are harmful.7,8 Some lipid changes are considered to be a reversal of infection-related effect as a result of immune reconstitution by treatment. There have been a few prospective studies evaluating lipid-lowering therapy in HIV-infected patients that suggest that treatment may improve lipid levels. A study by Calza et al showed that fibrate and statin therapy significantly lower triglycerides (by 35%–40%, P < 0.001) and total cholesterol (by 21%–25%, P < 0.001) over 12 months with a maximal benefit noted after 6 months of therapy. However, interactions with the combination of statins and PIs have shown increase in levels of statins, in particular, simvastatin. Therefore, the potential toxicity associated with this combination of drugs, such as myopathy and rhabdomyolysis, leads us to consider alternatives for the management of hyperlipidemia in this population. Here we present the case of a patient with ART-associated hypertriglyceridemia whose lipid disorder was satisfactorily managed with pioglitazone 60 mg daily.