Randomized, controlled, 48-week study of switching stavudine and/or protease inhibitors to combivir/abacavir to prevent or reverse lipoatrophy in HIV-infected patients.
OBJECTIVE
HIV-1 protease inhibitors (versus no protease inhibitors) and stavudine (versus zidovudine) are independently associated with a higher risk of lipoatrophy in HIV-infected patients. We sought to determine whether the revision of stavudine and/or protease inhibitor-containing regimens to combivir/abacavir would result in prevention and/or reversibility of lipoatrophy in HIV-1-infected patients.


METHODS
The investigation was a prospective, randomized, controlled, open-label study.


METHODS
The subjects included 37 HIV-1-infected individuals with stable undetectable HIV-1 loads who were taking a regimen containing either stavudine or zidovudine with lamivudine and a protease inhibitor.


METHODS
Subjects were randomized to continue therapy or switch stavudine to zidovudine and protease inhibitor to abacavir, such that the universal switch regimen was combivir (zidovudine/lamivudine) and abacavir.


METHODS
Total body, leg, and arm fat mass was measured at baseline, 24 weeks, and 48 weeks using whole-body dual-energy x-ray absorptiometry. Single-cut L4 computed tomography and assays of multiple metabolic parameters were also performed.


RESULTS
There was an average gain in fat mass of 0.009 kg/(leg.mo) in switch patients versus a loss of 0.010 kg/(leg.mo) in controls (p =.04, on-treatment analysis) over 48 weeks. Significant arm fat restoration was observed in patients who switched regimens, with an average gain of 0.014 kg/(arm.mo) (p =.004), whereas controls did not have a significant change from baseline. Analyses of percentage changes in arm and leg fat masses showed similar findings. No significant effects on intraabdominal fat, blood lipid levels, glycemic indices, and lactate levels were detected, although most baseline mean values were normal in study subjects. Combivir/abacavir maintained virological control in all but one case, and three (13.6%) of 22 individuals had adverse reactions to abacavir therapy.


CONCLUSIONS
A switch to combivir/abacavir therapy was associated with objective evidence of limb fat-sparing and fat restoration compared with continued treatment with stavudine and/or protease inhibitor.
John
Mina
M
Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Western Australia, Australia.
McKinnon
Elizabeth J
EJ
James
Ian R
IR
Nolan
David A
DA
Herrmann
Susan E
SE
Moore
Corey B
CB
White
Alex J
AJ
Mallal
Simon A
SA
D000328:Adult; D001823:Body Composition / Q000187:drug effects; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000150:complications* / Q000517:prevention & control*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018119:Stavudine / Q000009:adverse effects / Q000627:therapeutic use*; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*; D000099227:Abacavir
D015224:Dideoxynucleosides; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D019259:Lamivudine; D018119:Stavudine; D015215:Zidovudine; D000099227:Abacavir; C109078:lamivudine, zidovudine drug combination