Switch to tenofovir from AZT or d4T improves fat loss and improves lipid parameters compared to abacavir

One of the most publicised UK studies at the conference included an oral presentation of the RAVE Study. This is a switch study comparing differences in fat recovery and lipid parameter when using tenofovir or abacavir in patients with lipoatrophy who are changing from AZT or d4T. Results presented by Graeme Moyle from the Chelsea and Westminster Hospital showed that tenofovir was associated with fewer treatment discontinuations and greater improvements in lipid parameters.

Previous switch studies have shown that removing AZT or d4T from regimens can lead to an improvement in some lipoatrophy symptoms, and prospective data have suggested that neither abacavir nor tenofovir DF (TDF) is associated with lipoatrophy.

This was a randomised, open-label 48-week study using abacavir 300mg twice daily vs. TDF 300mg once daily in adults on HAART with moderate to severe lipoatrophy who had viral loads <50 copies/mL and who were naïve to the replacement drugs. Limb fat was measured by DEXA for primary endpoint and CT for secondary endpoint.

They randomised 71 adults receiving d4T and 34 receiving AZT to receive abacavir (n=53) or TDF (n=52).

Limb fat mass was similar in both groups at baseline, and there was a significant increase in both groups at 48 weeks (+0.5 kg vs +0.3 kg) with no difference between the two groups (p = 0.36). Similar changes in visceral fat and subcutaneous abdominal fat were observed by DEXA and CT scan. Virological suppression and CD4 impact were also similar in both groups.

Differences between the two arms in the ITT analysis was driven by six discontinuations in the abacavir arm, including 3 with hypersensitivity reactions, compared to just one in the TDF arm.

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 abacavir and –0.46 (1.11), –0.25 (0.72), and –0.49 (1.87) mmol/L with TDF. The changes in these parameters over 48 weeks showed TDF was associated with significantly greater lipid improvements (p=0.01, 0.05 and 0.01 respectively).

Moyle G, Sabin C, Cartledge J et al. A 48-week, randomised, open-label comparative study of tenofovir DF vs abacavir as substitutes for a thymidine analogue in persons with lipoatrophy and sustained virological suppression on HAART. 12th CROI, Boston, 2005.
Abstract 44LB.