Background:  The optimal management of HIV-related dyslipidemia is unknown. We hypothesized that fenofibrate (F) and pravastatin (P) are equivalent with respect to clinical response and safety in the treatment of HIV-related dyslipidemia and that dual therapy with F and P would provide added benefit in subjects with inadequate responses to monotherapy.

Methods:  A randomized, open-label, 48-week clinical trial. HIV-infected persons with dyslipidemia (LDL >130 mg/dL and TG >200 mg/dL) on ART for >6 months were randomized to receive either F 200 mg or P 40 mg by mouth daily. Subjects who had failed to reach a modified National Cholesterol Education Program (NCEP) goal (a composite of LDL, HDL, and TG levels, taking into account preexisting cardiovascular risk factors) by week 12 received both P and F and were followed for a total of 48 weeks.

Results:  We randomized 88 subjects to receive F and 86 to receive P. These single-agent results were reported at IAS 2002. Of 88 subjects, 60 who were randomized to F subsequently added P (FP), and of 86 subjects on P, 63 added F (PF); lipid data were available at week 48. At week 48, 4 (7 %) subjects on FP achieved the NCEP composite goal and 2 subjects (3%) on PF achieved goal; 8 (13%) of FP subjects met LDL goal; 9 (14%) of PF recipients met LDL goal; 40 (67%) of subjects on FP met HDL goals; and 35 (56%) of subjects on PF met HDL goal. For triglycerides, 36 (60%) of subjects on FP met the goal, and 28 (44%) of subjects on PF met it. Median changes from baseline in LDL/HDL/TG/non-HDL were -8/+4.5/-143.5/-50 and -14/+2/-66/-34 mg/dL in subjects receiving FP and PF, respectively. Median percentage changes in LDL/HDL/TG/non-HDL were -5/+17/-45/-21 and -8/+6/-25/-16 in subjects receiving FP and PF, respectively. The median percentage change in LDL in the P arm only at week 12 was 20% whereas it was 8% at week 48. There was a significant difference in both absolute and percentage reduction of triblycerides in subjects receiving F first compared with those who started with P initially (p = 0.019, p = 0.004, respectively). After week 12, 3 subjects discontinued the study for protocol-defined toxicities. There were no reports of rhabdomyolysis.

Conclusions:  Combination therapy with F and P for HIV-related dyslipidemia appears safe but unlikely to achieve composite NCEP goals. Sequencing therapy with F first results in a significantly greater reduction of triglyceride compared with starting with P. Adding F to P diminished the LDL-lowering activity of P alone and provided less triglyceride-lowering activity than achieved by adding P to F.

Keywords: dyslipidemia; statin; fibrate