Patients switching from anti-HIV drug regimens containing AZT (zidovudine, Retrovir) or d4T (stavudine, Zerit) may show better improvements in blood fat levels when they switch to tenofovir (Viread) than when they switch to abacavir (Ziagen), according to the latest data from the RAVE study. These findings were presented last month at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington.
The RAVE study was designed to examine the effects of replacement of the thymidine analogues AZT or d4T with either tenofovir or abacavir on the amount of fat under the skin in patients with moderate to severe fat loss. Fat loss, or lipoatrophy, is a common side-effect of thymidine analogues, that can be disfiguring.
A previous conference presentation showed that while fat loss was reversed by both tenofovir and abacavir, the two drugs’ effects differed according to the thymidine analogue the patients had previously taken. Patients who had been taking AZT showed better recovery of limb fat when they switched to abacavir. In contrast, those who had been taking d4T showed better recovery of limb fat when they switched to tenofovir.
The new data extend these findings by examining the effects of switching on the levels of fats in the blood: elevations in cholesterol and triglyceride levels can also occur in patients taking thymidine analogues. The new findings demonstrate that tenofovir may have an additional benefit of modestly reducing raised blood fat levels, while abacavir has little effect.
After 48 weeks, total cholesterol levels had fallen by a mean of 0.5mmol/l (19.3mg/dl) in the patients randomised to switch to tenofovir. In contrast, those switching to abacavir showed a mean rise of 0.2mmol/l (7.7mg/dl) (p = 0.003).
Levels of low-density lipoprotein (LDL or ‘bad’) cholesterol also fell by a mean of 0.3mmol/l (11.6mg/dl) in the tenofovir arm, compared to a mean rise of 0.1mmol/l (3.9 mg/dl) in the abacavir arm (p = 0.04).
Similar patterns were seen for high-density lipoprotein (HCL or ‘good’) cholesterol and triglyceride levels, but these were not statistically significant.
The beneficial effect of switching to tenofovir was also demonstrated by the use of lipid-lowering therapy by patients taking part in the study. While only one (2%) of the 52 patients switching to tenofovir started taking lipid-lowering therapy after 273 days, eight (15%) of the 53 patients switching to abacavir started lipid-lowering therapy after a median of 92 days.
Although they did not present the results of statistical analyses, the investigators observed that the falls in blood fats tended to be greater in the patients who switched from d4T. “Falls in total cholesterol and triglycerides were predominantly seen in individuals on d4T at baseline,” they write.
While this effect may be partly due to the higher blood fat levels in the d4T group at the time of the switch, these results suggest that replacing d4T with tenofovir may offer the more powerful strategy for reversing fat loss and preventing blood fat levels. In contrast, switching to abacavir may be of less benefit in correcting raised blood fat levels, while the effects of switching from AZT to either drug may have little effect on blood lipid levels.
“In lipoatrophic HIV-infected adults, switching from a thymidine analogue to abacavir or tenofovir for 48 weeks improves lipoatrophy,” the investigators conclude. “Modest benefits on lipids are observed in the tenofovir group.”
This study was supported by tenofovir’s manufacturer, Gilead Sciences.
Moyle G et al. Lipid changes in a randomised, 48-week, open label comparative study of tenofovir DF vs. abacavir as substitutes for a thymidine analog in persons with lipoatrophy: the RAVE study. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, abstract H-340, 2005.