Do women suffer more HIV drug side effects than men? That’s the latest concern to rattle female nerves -- literally. At last July’s International AIDS Conference in Barcelona, Emory University researchers reported that women on combination therapy had “significantly” more neurologic problems (such as nerve damage) and more lipodystrophy (a catch-all for abnormal fat loss and gain) than men. Other research into women and HAART suggests uniquely female liver damage, lipid and bone harm, and diabetes.

The news about side effects follows years of reports that women’s bodies respond differently to both HIV and the meds, though why remains a mystery. Whether the culprit is physiology, hormones, genes, a lack of access to health care or all of the above, there is growing evidence that women may get sick and die faster, have lower initial viral load levels and respond more quickly to treatment than men do -- even though the details are exasperatingly contradictory. Other studies show that various meds penetrate women’s genital tracts differently. What does all this mean for women on combo therapy, or considering it? For now, mostly confusion and worry, but no clear treatment guidelines. The most experts can recommend is vigilance -- careful monitoring of your bloodwork every three months, with special attention to cholesterol, sugar, fat and bone-density levels.

None of this female trouble surprises Kathy Anastos, MD, a leading HIV doc at Lincoln Hospital in the Bronx, New York. At 52, she’s a veteran physician and administrator at Lincoln and the leading New York investigator of the national Women’s Interagency HIV Study (WIHS). After much activist hell-raising, the feds launched this study in 1993 to address research gaps and collect clinical proof that, in HIV treatment, gender does matter.

A year ago, Anastos began studying med-related side effects, specifically metabolic toxicities, in 300 WIHS women. Using fancy imaging tests like whole-body DEXA body scans, her team measures bone density (for osteopenia and osteoporosis), glucose intolerance (which leads to diabetes), and cholesterol and fat (lipodystrophy) levels. Most of her HIVers are women of color, mainly African Americans. “Within a year, we’ll know who is getting what, then we can look at the mechanism [cause], like bone-turnover markers [measurements of bone cell growth and loss that define osteoporosis],” she says. “But first, let’s define the problem.”

Another WIHS team’s preliminary data show a very scary increase in cases of diabetes in women of color on combo therapy. Anastos says these new data worry her and deserve more study. “The side effects are bizarre and unanticipated,” she adds. “They’re significant, not just clinically, because it’s harmful to the health directly, but also psychologically. Like the fat distribution. I have several women who have that, and it is very distressing.” Turning to the subject of bones, she says, “All this stuff with osteoporosis is disturbing because it’s generally a disease of women, so women with HIV are at even greater risk. But it’s not clear that they are having more fractures.”

Fat is one front where Anastos has not seen a big difference between women and men. But she has noted disparities between the races. “It could be gender, but it could be racial factors, too,” Anastos says. “There’s a whole series of things that are probably genetically determined. And if you’re comparing black women to white men, you have no idea where the difference is coming from.” To this day, of course, much of the information we have about how HIV drugs work comes from the bodies of gay white men in the West. How does their experience reflect that of a woman with HIV in the Bronx, let alone Botswana? “Look around the world,” Anastos says. “Half the people with HIV are women of color. They should be studied, considering a whole lot of them are about to go on treatment.”

And yet Anastos thrills to the challenges ahead. “I think WIHS is on the edge of an explosion of knowledge, actually, about the differences by gender, race and the determinants of disease, not just in HIV, but in asthma, maybe diabetes.” That means that three days a week, Anastos wakes up extra early, her mind racing: “I think, ’Oh good, this is a WIHS day, and I get to sit and work, work, work.’” She laughs. “To me, that’s just great.”