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A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy

Moyle, Graeme Ja; Sabin, Caroline Ab; Cartledge, Jonathanc; Johnson, Margaretb; Wilkins, Edmundh; Churchill, Duncani; Hay, Philipd; Fakoya, Adee; Murphy, Mauricef; Scullard, Georgeg; Leen, Cliffordj; Reilly, Geraldinek; for the RAVE (Randomized Abacavir versus Viread Evaluation) group UK

doi: 10.1097/01.aids.0000247574.33998.03
Clinical Science

Background: Long-term antiretroviral therapy, while dramatically reducing HIV-related morbidity and mortality, is associated with metabolic and morphological changes. Peripheral fat loss, lipoatrophy, appears most associated with prolonged therapy with thymidine nucleoside analogues.

Methods: A randomized, open-label, comparative study of switching from a thymidine nucleoside analogue to either tenofovir disoproxil fumarate (DF) or abacavir in 105 individuals on successful antiretroviral therapy with clinically evident moderate to severe lipoatrophy.

Results: Individuals were randomized to tenofovir DF (52) or abacavir (53). The switch was well tolerated and the majority of patients completed 48 weeks of study. One individual in the tenofovir DF group and three in the abacavir group discontinued due to drug-related adverse events. Both groups similarly maintained virological control. Limb fat mass increased similarly in both groups: mean increases by week 48 of 329 and 483 g in tenofovir DF and abacavir groups, respectively [mean 95% confidence interval for difference, −154.3 (range −492.8 to 184.3)]. This change from baseline was statistically significant in both groups (tenofovir DF, P = 0.01; abacavir, P = 0.0001). Mean total cholesterol, low density lipoprotein cholesterol and triglycerides improved modestly with switching to tenofovir DF but were unchanged with abacavir. The changes in these parameters were significantly greater in the tenofovir DF arm relative to abacavir.

Conclusions: Switching from a thymidine nucleoside analogue to either tenofovir DF or abacavir leads to significant improvement in limb fat mass over 48 weeks. Tenofovir DF may have modest advantages over abacavir for changes in lipids. Peripheral lipoatrophy, when clinically apparent, resolves slowly following treatment switching.

From the aChelsea and Westminster Hospital, London

bRoyal Free & UC Medical School, London

cCamden Primary Care Trust, London

dSt Georges Hospital, London

eNewham General Hospital, London

fBarts and the London NHS Trust, London

gSt Mary's Hospital, London

hNorth Manchester Hospital, Manchester

iBrighton and Sussex University Hospital, Brighton

jWestern General Hospital, Edinburgh

kGilead Sciences, Cambridge, UK.

Received 23 May, 2006

Accepted 04 July, 2006

Correspondence to Dr G. J. Moyle, Chelsea and Westminster Hospital, 369 Fulham Rd, London, SW10 9NH, UK. E-mail:

© 2006 Lippincott Williams & Wilkins, Inc.