SHIV susceptibility changes during the menstrual cycle of pigtail macaques

Abstract

Background: Hormonal changes during menstrual cycling may affect susceptibility to HIV.

Methods: We determined the simian human immunodeficiency virus (SHIV) acquisition time point in 43 cycling pigtail macaques infected by repeated vaginal virus exposures initiated randomly in the cycle.

Results: SHIV infection was first detected in the follicular phase in 38 macaques (88%), and in the luteal phase in five macaques (12%), indicating a statistically significant timing difference. Assuming a 7-day eclipse phase, most infections occurred during or following a high-progesterone period associated with menstruation, vaginal epithelium thinning, and suppressed mucosal immunity.

Conclusions: This raises questions whether other high-progesterone conditions (pregnancy, hormonal contraception) similarly affect HIV risk.

Keywords: HIV acquisition; HIV risk; hormonal contraception; menstrual cycle; mucosal immunity; reproductive hormone.

Figure 1. Progesterone levels and SHIV infection

A–L: Each graph depicts plasma progesterone levels for one macaque, used to identify day one of the menstrual cycle (defined at steepest drop in progesterone). Cycles lasted until the next progesterone drop occurred. Negative days indicate that day one of the cycle could not be determined because no initial drop in progesterone was recorded. The first arrow (and accompanying asterisk at menstrual cycle day) indicates initiation of virus exposures, the second arrow (and asterisk) refers to time point of initial viremia > 49 copies/ml, except for in 1H and 1K, where it indicates the last virus challenge. Only data are shown that have not been reported elsewhere.

Figure 2. SHIV infection in relation to the menstrual cycle

A. The figure shows the number of macaques with detected infections during each day of the menstrual cycle. Three uninfected animals are not shown. B. Time of infection was calculated by subtracting a seven-day viral eclipse phase from the data shown in A. C. Schematic depiction of reproductive events during the cycle, and select physiologic processes with suspected effect on HIV susceptibility.

Figure 3. SHIV infection in relation to the menstrual cycle in a subset of macaques with twice weekly virus exposure and progesterone analysis

A. The figure shows data from 20 macaques with virus exposures and sample collection performed twice per week (as opposed to once per week). The number of macaques is given with detected infections during each day of the menstrual cycle. B. Time of infection was calculated by subtracting a seven-day viral eclipse phase from the data shown in A.