• CT Scan Findings at 48 Weeks Confirm Further Regression of Lipoatrophy (LA) Following the Substitution of Stavudine (d4T) With Either Abacavir (ABC) or Zidovudine (ZD4) (Abstract H-1929)
  Authored by S. Hessenthaler, G. McComsey, D. Ward, T. File, S. Ross, J. Hernandez
  Poster Presentation: View the original abstract

Increasing evidence has accumulated over the last few years to suggest that the thymidine analogues stavudine (d4T, Zerit) and zidovudine (AZT, ZDV, Retrovir) are associated with lactic acidosis and with fat atrophy in the face, arms and legs. In many studies, stavudine appears worse than zidovudine. Other nucleosides, including lamivudine (3TC, Epivir) and abacavir (ABC, Ziagen) appear to have less effects on lactic acid and fat atrophy. Although lipoatrophy appears to develop fairly slowly, most studies have suggested that it is very slow to improve when the offending agent is removed. In contrast, elevated cholesterol and triglycerides improve fairly quickly after switching drugs. This can be very frustrating for patients and their physicians.

The TARHEEL study examined the effects of substituting abacavir or zidovudine for stavudine in patients with lipoatrophy. Those who had been on zidovudine before substituted abacavir for stavudine. Those who had never been on zidovudine either started zidovudine (as Combivir) or abacavir. Roughly 75 percent substituted abacavir; the remainder started zidovudine.

A total of 118 patients were enrolled. At 12, 24 and 48 weeks after switching, patients in the study underwent DEXA to look at the change in fat in their arms, legs and abdomen. Over one year, there was a 25-30 percent increase in fat in their arms, and a 20 percent increase in leg fat. Fat in the abdomen also increased, but most of it was subcutaneous fat -- the normal place to accumulate fat. Visceral fat within the abdomen that is seen with protease inhibitors did not increase. CT scans confirmed the DEXA results.

Patients reported mild improvement in the way they looked. Nineteen to 27 percent felt that the fat wasting in their face, arms, legs or abdomen had increased at least somewhat.

It is important to put these improvements in perspective. The changes were modest and fairly slow. However, at 48 weeks there was ongoing improvement, so there may be further changes in the next year. It is reassuring to see at least some improvement with switching, but it would be nice to see more rapid changes. One might suspect that improvements would be more dramatic with abacavir or tenofovir (TDF, Viread) than zidovudine, but the numbers of patients on zidovudine were too small to draw any conclusions.

While encouraging, it would be nice to see more definitive and satisfying improvements for those patients who feel their appearance has changed.