Pitavastatin Emerges as a Preferred Drug for Dyslipidemia Treatment in Patients with HIV: INTREPID Study

The 1-year results of INTREPID, a phase 4 randomized, double-blind, active-controlled trial, has found that pitavastatin is superior to pravastatin in reducing low-density lipoprotein (LDL) cholesterol in patients with human immunodeficiency virus (HIV) by an 8% to 10% difference, according to results published in The Lancet HIV.

Patients with HIV are at greater risk for cardiovascular disease than individuals who are seronegative, they are at a 1.5 to 2 times higher risk for myocardial infarction, and up to 80% of patients with HIV report having dyslipidemia.

“A unique pathophysiology of atherosclerosis in the setting of HIV highlights the need for tailored primary cardiovascular disease prevention strategies in this population,” the study authors, led by Judith A. Aberg, MD, wrote. “Regardless of the biological cause of dyslipidemia, the challenge is how best to manage this disorder in people living with HIV.”

The purpose of the INTREPID (HIV-infected patieNts and TREatment with Pitavastatin vs pravastatin for Dyslipidemia) study was to compare the safety and efficacy of pitavastatin 4 mg versus pravastatin 40 mg in adult patients with HIV and dyslipidemia.

For inclusion into the study, patients had to be aged 18 to 70 years and to have been on antiretroviral therapy for a least 6 months before randomization. Further, they must have been stable on the therapy in the 3 months prior to study inclusion, and they also had to have CD4 counts of >200 cells per µl and HIV-1 RNA of <200 copies per mL.

At the 3-month time point, the patients randomly assigned to the pitavastatin group (n = 126) showed a 31.1% reduction in LDL, compared with a 20.9% reduction shown by the pravastatin group (n = 126), for a least squares mean difference of —9.8% (95% confidence interval –13.8 to –5.9; P < .0001). The initial 12-week results were followed by a 40-week safety extension period in which the benefits were sustained.

In addition to the reductions in LDL, patients in the pitavastatin group were also more likely to reach their LDL target at 12 and 52 weeks than the patients in the pravastatin group. In the pitavastatin group, 87% of the patients reached their target compared with 66% of the patients who reached theirs in the pravastatin group (P = .0123).

At week 52, there were no significant differences in CD4 cell counts or HIV-1 RNA. Virological failure occurred in 3% of the patients in the pitavastatin group compared with 5% of the patients in the pravastatin group.

There were no serious adverse events (AEs) reported for either group. AEs occurred in 68% of the patients treated with pitavastatin and 70% of the patients treated with pravastatin. Most were classified as mild or moderate in severity, and included 12 patients with diarrhea in the pitavastatin group and 14 patients with an upper respiratory tract infection in the pravastatin group.

“Dyslipidemia affects more than three-fourths of people with HIV, putting them at significantly increased risk for cardiovascular disease. However, treatment of elevated LDL cholesterol in this patient population is challenging because of drug interactions between statins and commonly used antiretroviral agents,” said Douglas Ward, MD, co-author of the INTREPID study publication, Clinical Associate Professor of Medicine at George Washington University Medical School, and physician at the Dupont Circle Physicians Group. “The finding that [pitavastatin] was more effective than pravastatin in lowering LDL cholesterol and was well tolerated in [HIV] patients with dyslipidemia suggests it could be a viable treatment option for managing dyslipidemia and contributing factors in adults with HIV.”

The study, “Pitavastatin versus pravastatin in adults with HIV-1 infection and dyslipidaemia (INTREPID): 12 week and 52 week results of a phase 4, multicenter, randomized, double-blind, superiority trial,” was published in The Lancet HIV.

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