Pravastatin Increased Subcutaneous Fat in HIV-Infected Men
Twelve weeks of pravastatin therapy significantly increased subcutaneous fat and had limited effects on plasma lipid parameters.
Switching antiretroviral regimens is currently the only effective means of treating HIV-related lipoatrophy. To evaluate whether pravastatin might also be beneficial, researchers conducted a randomized, placebo-controlled trial among 33 HIV-infected men in Australia who had been receiving PI-based therapy for at least 12 weeks and had fasting serum total cholesterol levels >6.5 mmol/L. At baseline, the men received dietary counseling and were randomized to receive placebo or pravastatin (40 mg daily) for 12 weeks, starting at week 4. The primary endpoint was time-weighted change in total cholesterol level from baseline to week 16. Secondary endpoints included regional fat levels and time-weighted change in cholesterol from week 4.
Of the 31 men who completed the study, 30 were on ritonavir-boosted PIs. When measured from baseline, time-weighted changes in cholesterol levels did not differ by treatment arm. When changes were measured from week 4, however, the pravastatin recipients had significantly greater declines in cholesterol levels than the placebo recipients. They also had significantly greater increases in both limb fat (0.72 vs. 0.19 kg) and abdominal subcutaneous fat. Except for homocysteine levels (which decreased significantly more with pravastatin than with placebo), there were no significant differences in other lipid, glucose, or cardiovascular parameters. No safety concerns were identified, and no effects were observed on HIV surrogate markers.
The finding that pravastatin led to a 0.72-kg increase in limb fat after just 12 weeks was somewhat unexpected, given the smaller increases seen in switch studies and the mixed or negative results seen in most studies evaluating treatments for lipoatrophy. For example, in the MITOX study, conducted by the same authors, patients experienced only a 0.39-kg increase in limb fat 24 weeks after switching from a thymidine analogue to abacavir. However, the patient population in the pravastatin study was unique: Most subjects were taking boosted PIs, with very few taking thymidine analogues. Although the pravastatin recipients had previously received thymidine analogues for a median of 293 weeks, the authors did not report when the subjects had switched off of these drugs. Further, the pravastatin recipients were all white males with a median age of 52, and 25% had been diagnosed with AIDS; previous studies have indicated that older age and a prior AIDS diagnosis are associated with higher risk for lipoatrophy. Given that a positive effect of statins on adipocytes is biologically plausible (through mechanisms such as the activation of sterol regulatory element-binding proteins), researchers should conduct larger follow-up studies to confirm these intriguing results in more heterogeneous patient populations.
Mallon PWG et al. Effect of pravastatin on body composition and markers of cardiovascular disease in HIV-infected men — A randomized, placebo-controlled study. AIDS 2006 Apr 24; 20:1003-10.
Gharakhanian S et al. Statins in HIV-associated lipodystrophy and metabolic syndrome: Is there a missing link? AIDS 2006 Apr 24; 20:1061-3.
Click here for AIDS Clinical Care subscription information.
Twelve weeks of pravastatin therapy significantly increased subcutaneous fat and had limited effects on plasma lipid parameters.
Summary and Comment
Summary
Switching antiretroviral regimens is currently the only effective means of treating HIV-related lipoatrophy. To evaluate whether pravastatin might also be beneficial, researchers conducted a randomized, placebo-controlled trial among 33 HIV-infected men in Australia who had been receiving PI-based therapy for at least 12 weeks and had fasting serum total cholesterol levels >6.5 mmol/L. At baseline, the men received dietary counseling and were randomized to receive placebo or pravastatin (40 mg daily) for 12 weeks, starting at week 4. The primary endpoint was time-weighted change in total cholesterol level from baseline to week 16. Secondary endpoints included regional fat levels and time-weighted change in cholesterol from week 4.
Of the 31 men who completed the study, 30 were on ritonavir-boosted PIs. When measured from baseline, time-weighted changes in cholesterol levels did not differ by treatment arm. When changes were measured from week 4, however, the pravastatin recipients had significantly greater declines in cholesterol levels than the placebo recipients. They also had significantly greater increases in both limb fat (0.72 vs. 0.19 kg) and abdominal subcutaneous fat. Except for homocysteine levels (which decreased significantly more with pravastatin than with placebo), there were no significant differences in other lipid, glucose, or cardiovascular parameters. No safety concerns were identified, and no effects were observed on HIV surrogate markers.
Comment
The finding that pravastatin led to a 0.72-kg increase in limb fat after just 12 weeks was somewhat unexpected, given the smaller increases seen in switch studies and the mixed or negative results seen in most studies evaluating treatments for lipoatrophy. For example, in the MITOX study, conducted by the same authors, patients experienced only a 0.39-kg increase in limb fat 24 weeks after switching from a thymidine analogue to abacavir. However, the patient population in the pravastatin study was unique: Most subjects were taking boosted PIs, with very few taking thymidine analogues. Although the pravastatin recipients had previously received thymidine analogues for a median of 293 weeks, the authors did not report when the subjects had switched off of these drugs. Further, the pravastatin recipients were all white males with a median age of 52, and 25% had been diagnosed with AIDS; previous studies have indicated that older age and a prior AIDS diagnosis are associated with higher risk for lipoatrophy. Given that a positive effect of statins on adipocytes is biologically plausible (through mechanisms such as the activation of sterol regulatory element-binding proteins), researchers should conduct larger follow-up studies to confirm these intriguing results in more heterogeneous patient populations.
Source
Mallon PWG et al. Effect of pravastatin on body composition and markers of cardiovascular disease in HIV-infected men — A randomized, placebo-controlled study. AIDS 2006 Apr 24; 20:1003-10.
Gharakhanian S et al. Statins in HIV-associated lipodystrophy and metabolic syndrome: Is there a missing link? AIDS 2006 Apr 24; 20:1061-3.
Click here for AIDS Clinical Care subscription information.
Source...