Fat loss from the limbs (lipoatrophy), caused by certain antiretroviral drugs, can be reversed in the long term by switching from AZT or d4T to abacavir, according to two-year data from a study published in the April 30th edition of AIDS. The investigators note, however, that switching from the thymidine analogues AZT and d4T was not associated with an improvement in any other aspects of the lipodystrophy syndrome, such as visceral fat accumulation, high blood lipids, or buffalo hump.
The Australian MITOX study randomised 111 HIV-positive patients with evidence of fat wasting from the limbs, who were taking a HAART regimen including AZT or d4T, to either switch the thymidine analogue for abacavir, or remain on AZT or d4T.
Data from week 24 showed that individuals switching to abacavir gained a significant amount of limb fat compared to individuals remaining on a thymidine analogue. These results were previously reported on aidsmap. Accordingly, patients who had been randomised to stay on AZT or d4T were offered the opportunity at this point to switch to abacavir, which 21 individuals did, with 22 patients opting to remain on AZT or d4T therapy.
Of the original 111 patients randomised, 85 remained on the study at week 104, and of these 77 had DEXA imaging scan assessments of body composition available at week 104.
Individuals who had switched to abacavir had a mean increase in limb fat at week 104 of 1.26kg (+/- 2.02kg) compared to 0.46kg (+/-1.38kg) for the patients who remained on a thymidine analogue. This difference was statistically significant (p=0.008).
Further analysis revealed that limb fat gain was greatest in those patients who had been randomised to receive abacavir from baseline. However, individuals’ self-assessment of lipodystrophy at week 104 not did differ significantly between the abacavir and thymidine analogue arms, and self-assessed changes in lipodystrophy correlated poorly with changes in limb fat observed using the DEXA scans.
In multivariate analysis, the investigators established that higher body mass index (BMI) at baseline was significantly associated with greater fat gain at week 104 (p=0.004). They also found a trend for longer duration of thymidine analogue therapy to be independently associated with lower increases in limb fat gain, although this trend did not reach statistical significance (p=0.055).
The investigators also conducted analyses to see if any other markers of lipodystrophy differed between the two arms of the study. They found that there was no significant difference in the decrease in visceral adipose tissue between the abacavir and AZT/d4T arms. There was also a similar prevalence of buffalo hump in the two arms of the study. Bone mineral density decreased slightly, but significantly, in the AZT/d4T-treated patients (p=0.008), but no such change occurred in the abacavir arm.
No differences in CD4 cell count, viral load, or blood lipids were observed between the two arms at week 104.
A total of ten serious adverse events were reported, including four cases of the abacavir hypersensitivity reaction in patients who switched from AZT or d4T after week 24.
The investigators comment that “overall, patients randomised to abacavir had greater recovery of limb fat mass compared with those remaining on thymidine analogues. However, there was no difference in [visceral adipose tissue], buffalo hump, self-assessed lipodystrophy,” or elevated blood lipids. They add that “this demonstrates that lipoatrophy can be abrogated using this switching strategy, but the overall features of lipodystrophy syndrome may not. The study findings further support a causal role for thymidine analogues in the pathogenesis of the lipodystrophy syndrome.”
Further information on this website
Lipodystrophy - overview
Lipodystrophy - factsheets
Two years after switch to abacavir, only one third of limb fat returns - earlier reporting of this study
Stopping d4T or AZT may reverse fat loss – slowly - earlier reporting of this study
Martin A et al. Reversibility of lipoatrophy in HIV-infected patients 2 years after switching from a thymidine analogue to abacavir: the MITOX Extension Study. AIDS 18: 1029-1036, 2004.