Possible Increased Tenofovir Exposure in Post-Menopausal Women

At the 18th Conference on Retroviruses and Opportunistic Infections (CROI), held in Boston from February 27 through March 2, 2011, findings were presented from a study examining the level of tenofovir (Viread®) in the blood and vaginal fluid of pre- and post-menopausal women infected with HIV.

Understanding how changes in the body due to menopause impact antiretroviral (ARV) exposure is critical considering the aging population, since an increasing number of older women will be living with HIV. In addition, new HIV infections have been increasing in women over 50 in the U.S. Another study presented at CROI 2011 showed that lower levels of estrogen production after menopause, along with changes in the vagina, may increase susceptibility to HIV infection.

The study measured steady-state drug levels after four weeks on tenofovir and emtricitabine. The 12 pre-menopausal women were studied first, followed at a later date by the 6 post-menopausal women in the study. After the first dose, tenofovir exposure was similar in the blood for pre- and post-menopausal women, but higher in the vaginal fluids of post-menopausal women. After four weeks, post-menopausal women had significantly higher levels of tenofovir in both the blood and vaginal fluids.

The study found that the blood and genital tract levels of tenofovir are significantly increased in post-menopausal women receiving chronic tenofovir. These findings may be significant because previous studies have suggested that tenofovir, widely used as part of combination ARV treatment for treating HIV infection, is associated with bone loss. Post-menopausal women are inherently more susceptible to bone loss. Thus, increased drug levels may be a reason for concern about bone loss in post-menopausal women with HIV who are on tenofovir.

The researchers noted that they only looked at drug levels in pre-menopausal women during the first phase of their menstrual cycles. It would also be informative to look at drug levels in pre-menopausal women during the second (lower-estrogen) phase of their menstrual cycle, to study the true impact of reduced estrogen on tenofovir levels. Furthermore, the small number of women studied may not have been enough to reach a definitive conclusion. In reference to the results from their study, the researchers stated, “This suggests that aging and the associated physiological changes affect systemic drug disposition, but also drug penetration into sanctuary sites. Further investigation into the cause of these alterations is warranted.”