Pravastatin, Rosiglitazone, and Growth Hormone Fail as Treatments for HIV-related Lipoatrophy

Lipoatrophy -- loss of fat in the face and limbs -- is a problem for many HIV positive people on HAART, and treatment options remain limited. Beyond switching to a thymidine-sparing regimen, few interventions have shown reliable benefit. Recent studies suggest glitazone and statin drugs may help restore fat; growth hormone may have a beneficial effect on body composition, but can worsen insulin resistance.

As reported at the recent ICAAC, the HALT (HIV-Associated Lipoatrophy Treatment) Study enrolled 60 HIV positive men with lipoatrophy, who were randomly assigned to one of 5 once-daily treatment arms:

pravastatin (Pravachol), 40mg for 48 weeks;
rosiglitazone (Avandia), 4 mg for 48 weeks;
pravastatin plus rosiglitazone for 48 weeks;
recombinant human growth hormone (rhGH, Serostim), 2mg for 12 weeks;
rhGH plus rosiglitazone for 12 weeks.

Participants were assessed every 12 weeks with tests including dual energy X-ray absorptiometry (DEXA), computed tomography (CT), biochemistry, and clinical anthropometrics.

Results

Neither pravastatin nor rosiglitazone, either alone or in combination, affected measures of body composition by DEXA, CT, or clinical criteria.

rhGH resulted in significant reduction in visceral abdominal fat (by 26%, or 31 cm2) by CT and trunk fat (by 27%, or 1597 g).

rhGH increased trunk and limb lean body mass by DEXA (by 10% and 12%, respectively) after 12 weeks, but the effects were almost completely reversed within 12 weeks after discontinuation.

Adding rosiglitazone to rhGH abrogated the insulin resistance seen with rhGH alone.

Total and LDL cholesterol were reduced in the pravastatin arm (by 1.3 and 1.2 mmol/L, respectively), but were unaffected by other therapies.

Conclusion

The researchers concluded that, "Neither pravastatin nor rosiglitazone are effective therapies for body composition changes in [HIV-associated lipoatrophy syndrome]." They added that, "rhGH is effective at reducing visceral fat and its deleterious effects on insulin resistance can be reduced by co-administration of rosiglitazone but its effects are short-lived."

St George's, Univ. of London, London, U.K.; Chelsea & Westminster Hosp., London, U.K.

10/10/06

Reference
D C Macallan, S Mandalia, G Panayiotakopoulos, and others. Comparison of the Effects on Body Composition of Rosiglitazone, Pravastatin, and Growth Hormone Alone and in Combination in the HIV-Associated Lipoatrophy Treatment (HALT) Study. 46th ICAAC. San Francisco, CA. September 27-30, 2006. Abstract H-1897.

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