Background:  Peripheral lipoatrophy and dyslipidemia may complicate antiretroviral therapy. Switch studies have demonstrated that lipoatrophy may improve when a thymidine analog is removed from the regimen. Prospective data suggest that neither abacavir (ABC) nor tenofovir DF (TDF) is associated with lipoatrophy.  Our objective was to compare ABC with TDF when substituted for zidovudine (AZT) or stavudine (d4T) with regards to limb fat recovery, change in lipids and control of HIV RNA.

Methods:  A randomized, open-label, 48-week study of change in limb fat following substitution of AZT or d4T with ABC (300 mg twice daily) vs TDF (300 mg once daily) in adults on HAART with moderate to severe lipoatrophy who are naive to ABC and TDF with a current viral load < 50 copies/mL. Limb fat was measured by dual-energy x-ray absorptiometry (DEXA); secondary end points included HIV RNA, adverse events, visceral fat mass (by CT scan), and fasting metabolic parameters. Analyses were performed on an intent-to-treat basis ignoring treatment changes.

Results:  We randomized 105 adults receiving d4T (n = 71) or AZT (n = 34):  53 to ABC, 52 to TDF. Limb fat mass was similar at baseline (mean [SD]:  3.7 [2.2] kg in ABC and 3.9 [2.2] kg in TDF). At week 48 there was a significant increase in limb fat in both groups from baseline values (p < 0.01) but no difference between drug arms (increases of 0.5 vs 0.3 kg; p = 0.36, difference in means: 0.2, 95% confidence interval: –0.2, 0.5).  Similar changes in visceral fat (p = 0.32) and subcutaneous abdominal fat (p = 0.78) by CT were observed. Virological suppression was similarly maintained between both groups (p = 0.16). Discontinuation of drug was more common with ABC (n = 6, including 3 hypersensitivity reactions) than TDF (n = 1). Mean changes (SD) in total cholesterol, LDL and triglycerides were 0.31 (1.15), 0.10 (0.93), and 0.46 (1.83) mmol/L with ABC and –0.46 (1.11), –0.25 (0.72), and 0.49 (1.87) mmol/L with TDF. Changes in each parameter through week 48 significantly favoured TDF (p = 0.01, 0.05 and 0.01, respectively). No significant differences between treatment groups were observed in changes in bone mineral density scores by DEXA.

Conclusions:  In lipoatrophic HIV-infected adults, switching from a thymidine analog to ABC or TDF for 48 weeks leads to similar, significant increases in limb fat. While both agents maintain virological suppression, TDF is associated with fewer treatment discontinuations and greater improvements in lipid parameters than ABC.

Keywords: Lipoatrophy; Tenofovir DF; Abacavir