Cyclic changes in HIV shedding from the female genital tract during the menstrual cycle

Worldwide, most new cases of human immunodeficiency virus (HIV) infection among adults occur during heterosexual exposure, while maternal-to-child transmission is the primary cause of new infections among children. Transmucosal infection is therefore a critical driver of the global HIV epidemic. The risk of mucosal transmission is correlated with both plasma and genital HIV RNA levels, and each log10 increase in genital HIV type 1 (HIV-1) RNA is associated with a 2.20fold increase in the risk of female-to-male transmission [1]. It is therefore of considerable importance to HIV prevention efforts to elucidate biological variables and exogenous factors that influence HIV-1 shedding from the female genital tract. In reproductive-aged women, one potentially important factor affecting viral shedding is the physiologic fluctuation in hormone levels and associated changes occurring during the menstrual cycle. Recent studies suggest that women using hormonal contraceptives may be more likely to acquire and transmit HIV than women not using hormonal contraceptives. Although these findings may be due partly to behavioral differences, these and earlier results draw attention to the possibility that circulating hormone levels may affect viral shedding from the genital tract. However, human studies directly examining the relationship between menstrual cycle phase and genital shedding have been inconsistent, with some reports failing to demonstrate any correlation between menses and shedding [2–4] and others indicating a significant cyclic relationship, typically with peak shedding levels immediately prior to or during menses and nadir levels around the time of ovulation [5–7].