Limb fat gains lower when switching from AZT to abacavir or tenofovir, compared with d4T

People switching from AZT- (zidovudine, Retrovir) containing anti-HIV regimens to either tenofovir- (Viread) or abacavir- (Ziagen) containing regimens are significantly less likely to recover limb fat after 48 weeks compared with those who switched from d4T (stavudine, Zerit). Older age, white ethnicity and longer duration of anti-HIV therapy were also factors associated with less fat gain. The data were presented in November at the Tenth European AIDS Conference / European AIDS Clinical Society in Dublin.

Results of the RAVE Study, which substituted AZT or d4T with either abacavir or tenofovir in patients with moderate-to-severe lipoatrophy, were first reported at the 12^th Conference on Retroviruses and Opportunistic Infections (CROI) in February. In this study of 105 predominantly white males there was a significant 12% to 15% increase in limb fat from baseline after 48 weeks. However, limb fat increase, as measured by DEXA scans, was greater in those individuals who had switched from d4T rather than AZT.

In this follow-up presentation, Dr Graeme Moyle of London’s Chelsea and Westminster Hospital provided more details and an analysis of the factors associated with more limb fat gain. Median limb fat gain was similar when comparing the two drugs that participants switched to (393 vs. 316 grams on tenofovir or abacavir, respectively) a non-significant difference.

However, when analysed by the two drugs that partipants switched from, significant differences were seen. After 48 weeks the participants who replaced AZT gained only 66 grams of limb fat on tenofovir and 210 grams with abacavir. In contrast, the participants replacing d4T gained 529 grams of limb fat on tenofovir and 357 grams with abacavir.

Two multivariate analyses were performed in order to ascertain independent predictors associated with fat gains. Various factors were considered. These included randomisation group, age, sex, risk group, ethnicity, baseline CD4, nadir CD4, CDC status, baseline limb fat, baseline thymidine analogue, the number of antiretrovirals previously taken, time on therapy, weight at randomisation, and use of PI or NNRTI as third agent in the regimen.

Two factors were found to be associated with an absolute change in limb fat:

• Age at randomisation (for every five years older, a median of 103 grams less recovery was seen by week 48; p=0.07).
• Baseline thymidine analogue (baseline AZT treatment led to a median of 419 grams less fat recovery at week 48; p=0.02).

Three factors were found to be associated with greater than 710 grams of fat recovery over 48 weeks:

• Baseline thymidine analogue (AZT at baseline, Odds Ratio 0.15; p=0.01).
• Longer prior duration of anti-HIV therapy (Odds Ratio 0.75 per year; p=0.04).
• White ethnicity (Odds Ratio 0.17; p=0.01).

Dr Moyle pointed out that use of AZT at baseline was consistently associated with a low fat mass recovery and an 85% lower change of recovering greater than 710 grams over 48 weeks, relative to d4T use at baseline. “A similar effect was seen in the MITOX study,” he noted, “but there were few AZT patients in that study. Particularly in the abacavir group, the baseline limb fat was virtually identical in d4T- and AZT-treated patients. The hypothesis is that AZT is injuring fat cells differently to d4T."

Other factors associated with less fat recovery included older age, white ethnicity and longer duration of anti-HIV therapy. Dr Moyle concluded by suggesting an earlier switch away from d4T or AZT would improve the chances of gaining limb fat.