Background:  All protease inhibitors (PI) except atazanavir (ATV) are associated with adverse metabolic effects including hyperlipidemia. This trial evaluates the reversal of hyperlipidemia in HIV-infected patients switching any PI to atazanavir. Lipid reduction is associated with reduction of cardiovascular risk.

Methods:  This is a 48-week, open-label, randomized study that included subjects on a stable PI-containing (boosted or not) regimen with HIV RNA < 50 copies/mL and elevated fasting low-density lipoprotein cholesterol (LDL-C) (> 130 mg/dL). Patients were randomized to switch PI to ATV 400 mg daily (n = 126) or continue current PI (n = 118) with unchanged nucleoside reverse transcriptase inhibitors. The primary end point was the week 12 mean change in LDL from baseline. Secondary objectives included changes in other lipid parameters.

Results:  Greater decreases were observed for ATV in the following parameters (ATV - PI; 95% CI): LDL-C (–15%; –19.1%, –10.8%), total cholesterol (–18%; –20.4%, –4.6%), non–high-density lipoprotein cholesterol (HDL-C) (–22%; –25.2%, –18.5%), apolipoprotein B (–19%; –22.8%, –15.8%), lipoprotein a (–21%; –32.6%, –9.8%), and triglycerides (–35%; –41.8%, –26.5%). An increase in HDL-C was also observed with ATV. Virologic suppression was maintained, with 2 (ATV) and 1 (PI) viral load rebounds through week 12 (~40% were on ritonavir-boosted PI at baseline). Rates for all adverse events (ATV vs PI [67% vs 60%]), grade 3 to 4 adverse events (9% vs 10%), and adverse events leading to discontinuation (3% vs < 1%) were comparable. Of note, 1 patient discontinued due to ocular icterus (ATV) and another due to elevated transaminases (PI).

Conclusions:  Subjects with elevated lipids on PI-containing HAART who switched to ATV had improved lipid profiles over 12 weeks vs subjects who did not switch. ATV 400 mg daily maintained viral suppression. The study is ongoing through 48 weeks of follow-up.

Keywords: atazanavir; lipids; boosted