9th Conference on Retroviruses and Opportunistic Infections Seattle, Washington - February 24 -February 28, 2002

Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 32
A. Carr¹, D. Smith², C. Workman³, J. Hoy⁴, N. Doong⁵, J. Amin², M. Law², D. A. Cooper^1,2, and the MITOX Study Group
¹St. Vincent's Hosp., Sydney; ²NCHECR, Univ. of New South Wales, Australia; ³AIDS Res. Initiative, Sydney; ⁴Alfred Hosp., Melbourne; and ⁵Burwood Road Med. Ctr., Sydney, Australia

BACKGROUND: Peripheral lipoatrophy (LA) often complicates antiretroviral therapy, particularly nucleoside analogues (NRTIs), and may have a mitochondrial pathogenesis. LA may be a result of total duration of all NRTIs and/or NRTI type (perhaps mainly stavudine [d4T]). There is no proven therapy for LA. Abacavir (ABC) may be less toxic to NRTI mitochondria. A randomised study was performed to determine if LA might reverse following NRTI substitution with ABC.

METHODS: Adults with moderate/severe LA receiving d4T or zidovudine (AZT) with stable plasma HIV RNA < 400 copies/mL and no prior ABC therapy were randomised 1:1 to switch d4T or AZT to open-label ABC while continuing all other therapy or to continue all therapy. Primary endpoints were limb fat (DEXA and CT) and HIV RNA.

RESULTS: 111 patients were recruited and stratified by d4T (84%) vs AZT (16%) use, PI use (56%), and lactic acidemia (25%). 98% were male, mean age 44 years, mean CD4 count 577 cells/mm³, and mean NRTI duration was 5 years. The only severe ABC adverse event was hypersensitivity in 5 (10%) patients. There was a significant increase in limb fat in the ABC group relative to the continue group (0.39 and 0.08 kg, respectively; p=0.016), as well as significant (p<0.02) relative increases in subcutaneous thigh and abdominal fat areas. Peripheral fat increases were greater in ABC patients with higher limb fat mass or lactate < 2 mmol/L at baseline. There was no change, however, in patient-assessed LA severity and no correlation between changes in patient-assessed LA severity and limb fat mass. Switching to ABC resulted in relative declines in lactate (0.25 mmol/L; p=0.02) and plasma HIV RNA (0.25 logs; p=0.08). There was no significant effect on intra-abdominal fat, haematological, biochemical, lipid or glycaemic parameters, quality of life, or CD4 counts.

CONCLUSIONS: LA in HIV-infected adults improves, but does not normalise, and viral load remains stable, after switching to ABC from d4T or AZT for 24 weeks.

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