A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy.
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.
Moyle
Graeme J
GJ
Chelsea and Westminster Hospital, London, UK. gm@moyleg.demon.co.uk
Sabin
Caroline A
CA
Cartledge
Jonathan
J
Johnson
Margaret
M
Wilkins
Edmund
E
Churchill
Duncan
D
Hay
Philip
P
Fakoya
Ade
A
Murphy
Maurice
M
Scullard
George
G
Leen
Clifford
C
Reilly
Geraldine
G
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D050218:Body Fat Distribution; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D018119:Stavudine / Q000009:adverse effects; D000068698:Tenofovir; D015215:Zidovudine / Q000009:adverse effects; D000099227:Abacavir
D000225:Adenine; D019380:Anti-HIV Agents; D015415:Biomarkers; D015224:Dideoxynucleosides; D008055:Lipids; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D000068698:Tenofovir; D015215:Zidovudine; D000099227:Abacavir