A 48-week, randomized, open-label comparison of three abacavir-based substitution approaches in the management of dyslipidemia and peripheral lipoatrophy.
BACKGROUND
The mechanisms by which dyslipidemia and lipoatrophy develop during antiretroviral therapy are not clear. No treatment of lipoatrophy is currently established.


METHODS
This was an open-label randomized study of HIV-positive individuals on a first-line therapy containing stavudine (d4T) with either a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) and with hypercholesterolemia (defined as total cholesterol >5.2 mmol/L or >180 mg/dL) and/or lipoatrophy and with a viral load of <50 copies/mL. Patients switched d4T to abacavir (ABC) (group 1), a PI or NNRTI to ABC (group 2), or d4T and PI or NNRTI to ABC plus AZT (group 3). Patients were followed-up with fasting blood levels, dual-energy X-ray absorptiometry (DXA), and computed tomography (CT) scans for 48 weeks.


RESULTS
Thirty patients were included, with 27 completing 48 weeks of therapy. One ABC hypersensitivity reaction was the only serious adverse event. All patients' viral loads remained at <50 copies/mL. CD4 cell counts rose in groups 2 and 3 but fell modestly in group 1. Total and low-density lipoprotein cholesterol improved significantly in groups 2 and 3. Triglycerides fell significantly in group 2. In contrast, total, arm, and leg fat mass (by DXA) rose significantly in group 1 but fell modestly in groups 2 and 3. Visceral adiposity (by CT scan) was unaffected in all groups.


CONCLUSIONS
Abacavir represents a virologically effective replacement for d4T, PI, or NNRTI in persons on successful first-line therapy. Replacement of a PI or NNRTI with ABC leads to modest improvement in both cholesterol and triglycerides. Replacement of d4T with ABC leads to modest improvements in fat mass.
Moyle
G J
GJ
Chelsen and Westminster Hospital, London, Uned Kingdom. gm@moyleg.demon.co.uk
Baldwin
C
C
Langroudi
B
B
Mandalia
S
S
Gazzard
B G
BG
D000328:Adult; D001823:Body Composition / Q000187:drug effects; D015224:Dideoxynucleosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000150:complications* / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced / Q000150:complications* / Q000209:etiology / Q000517:prevention & control*; D007333:Insulin Resistance; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D000099227:Abacavir
D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D000099227:Abacavir