Doth the bell toll for Zerit, a.k.a. Bristol-Myers Squibb’s embattled nucleoside analog, d4T? First, it got a high-profile spanking at last year’s world AIDS confab, when a big fed-funded study showed that HIVers who started HAART on a d4T/ddI combo had more lipoatrophy (abnormal fat loss) in  arms and legs than those who started on an AZT/3TC combo. Then, last December —the same month the FDA approved a once-a-day version of Zerit—a study by France’s Agency for AIDSResearch reported that, among d4T-naïves with otherwise-equal time on HAART, roughly half of those on a Crixivan/3TC/d4T combo showed fat loss in the face, limbs and butt after two and a half years, compared to just less than a quarter of those on Crix/3TC/AZT.

This bad news for BMS no doubt delights archrival AZT-maker GlaxoSmith-Kline, which has funded other studies with similar results. But what’s the message for Dick and Jane HIVer? “Let’s face it,” says New York City’s Howard Grossman, MD, “the evidence is pretty overwhelming that d4T seems to be more associated with lipo than the other nukes, especially when combined with PIs.” But he notes that AZT doesn’t get off scot-free for lipo, either—findings that lead Boston’s Cal Cohen, MD, to call the difference between the two drugs “real” but “not huge.” And LA’s Mark Katz, MD, adds that age, years infected, time on meds and all-time CD4 low also factor into lipo risk.

What’s an HIVer to do? “Until GSK and BMS figure out what’s going on,” says Grossman, echoing other docs, “why not avoid both” in favor of less lipo-linked nukes, like 3TC and Viread? And if you just ain’t got a choice? Work with it, says San Fran’s Mary Romeyn, MD: “I’d rather need plastic surgery than an undertaker.”