Question

I have a female patient currently receiving stavudine (d4T) + lamivudine (3TC) + nevirapine (NVP) who is now concerned about body shape changes (lipodystrophy). What are the guidelines about substituting zidovudine (AZT) for d4T if AZT was discontinued due to severe anemia that required 2 blood transfusions? Is it advisable to switch back to AZT, and if not, what other agent would you advise?

Mulomba Enock, MD

Response from Douglas J. Ward, MD

Dupont Circle Physicians Group, Washington, DC

The pathogenesis of lipodystrophy is still poorly understood and is certainly more complicated than simply blaming it on specific medications. However, if your patient is concerned about developing lipodystrophy, then switching her off d4T, the drug most strongly associated with the fat loss (lipoatrophy) associated with this syndrome, is certainly reasonable.

AZT would be a good choice as an alternative to d4T; the TARHEEL trial showed improvement in lipoatrophy over 48 weeks in patients making this switch [1]. However, if your patient has a history of significant toxicity to AZT, other alternatives might produce better results. Abacavir (ABC) is probably the option with the most data to support its use in this context. In the MITOX trial, patients with lipoatrophy were switched from either AZT or d4T to ABC [2] [3]. Patients showed improvement in their lipoatrophy with continued virologic control up to 2 years after the switch.

Even without data that show improvement in existing body shape changes, other options exist that may reduce the risk of developing lipoatrophy. Tenofovir (TDF) and even didanosine extended release (ddI EC) are other potent reverse transcriptase inhibitors that could be substituted for d4T in this situation. As an added bonus, TDF, ddI EC, or ABC, given with NVP and 3TC, might allow for a regimen in which all agents are dosed once daily. (However, it is important to note that neither NVP nor ABC is yet FDA-approved for once-daily dosing).