Liver Damage

Liver Damage

Women are also at increased risk of liver damage related to nevirapine compared to men. In fact, according to reports from post-marketing surveillance of this drug, women with CD4 counts higher than 250 cells/mm3 had a 12-fold increased risk of developing clinically significant liver damage compared to women with CD4 counts less than 250. This is in stark contrast to men who had a five-fold increased risk of liver damage with higher CD4 counts (at greater than 400 cells/mm3) compared to men with lower CD4 counts.²⁵ In a study from South Africa of HIV patients on nevirapine, 20% of women compared to 12.8% of men had serious liver damage. Interestingly, 50% of the liver damage in the female group occurred in very thin women with body masses indices less than 18.5.²⁶

Fat Redistribution

Antiretroviral medications are well-known for their fat redistribution side effects, though this has been improving with more recent agents. However, women are uniquely affected by these side effects compared to men. This is likely due to a few reasons. First, women have more total body fat than men. And second, HIV-positive women tend to have more central obesity. However, women and men tend to have equal rates of fat loss from their extremities. Patients have described this fat pattern in women as resembling "beach balls on sticks." [See "Lipodystrophy and Women," May/June 2004 issue.] Further studies need to be done to understand the specific fat redistribution effects of ARVs in women, especially to determine if these changes could have detrimental effects on their overall health.

Bone Thinning

Osteoporosis is defined as decreased bone mineral density and abnormal architecture of bone that increases the risk of serious fractures, which are in turn associated with a higher risk of death over 5 to 10 years.

We already know that women in general are at increased risk of developing osteoporosis after menopause, but studies have also shown that HIV infection alone increases a person's risk of losing bone mineral density. This places both men and women infected with HIV at increased risk of osteoporosis.²⁷

HIV-positive women are at even higher risk, in fact approximately three times higher, for bone thinning than HIV-positive men. Other risk factors for HIV-positive individuals and bone loss include older age, lower body mass indices, higher viral loads, and lower CD4 counts.²⁸

There is some data to suggest that certain antiretrovirals may lead to bone mineral density loss. For example, two studies found that HIV-positive individuals on protease inhibitor (PI)-containing ARV regimens had higher rates of osteopenia and osteoporosis than HIV-positive individuals not on PI-containing regimens.

Tenofovir (Viread) has been associated with bone thinning over time in randomized studies, possibly related to phosphate wasting on this drug. A large study that randomized patients to continuous therapy versus intermittent therapy (the SMART study) showed that patients in the continuous antiretroviral arm had higher rates of bone loss than those on intermittent ARVs.

Most studies, however, show that HIV itself is a risk factor, whether or not antiretrovirals are implicated, and that higher viral loads, lower CD4 cell counts, and longer durations of HIV infection are associated with higher rates of bone mineral density loss, arguing that treatment of HIV infection is important in the prevention of osteoporosis. Many other studies have looked at standard osteoporosis treatments with bisphosphonates and calcium/vitamin D supplementation in HIV-positive patients on ARVs and have found these to be safe and effective treatments for osteoporosis. Most authors argue that vitamin D deficiency should be ruled out in any HIV-positive patient with significant osteoporosis to determine the need for extra supplementation.

The bottom line here is that women with HIV need to be screened for osteoporosis regularly, and that both the treatment of their HIV and regular treatment for osteoporosis are warranted.