Background: The menstrual cycle may influence susceptibility to cervicovaginal infections by regulating vaginal epithelial thickness, mucosal immune factors, and concentrations of infection target cells. Previous HIV susceptibility studies in pigtail macaques without sexually transmitted diseases (STDs) report enhanced SHIV susceptibility in the late-luteal menstrual cycle phase when progesterone levels are high. We seek to understand the mixed effect of STDs and menstrual cycle-related on susceptibility to HIV infection.
Methods: A pigtail macaque model of Trichomonas vaginalis (TV) – Chlamydia trachomatis (CT; serovar D) coinfection was used to study STD and menstrual cycle effects on SHIV susceptibility. Menstrual cycle phases in sixteen pigtail macaques were monitored with plasma progesterone levels and observing perineal tumescence (hormonally regulated sex swelling) and menses onset. Nine macaques were coinfected with TV-CT, confirmed by InPouch culture and Gen-Probe APTIMA testing (TV and CT, respectively). Seven macaques received sham inoculations. All macaques were repeatedly challenged intravaginally with low-dose SHIVSF162p3. Time point of first SHIV detection was confirmed by real-time PCR detection of plasma viral RNA.
Results: For TV-CT-coinfected animals (all 9 became SHIV-infected), SHIV RNA was first detected later in the menstrual cycle (median day 17), compared to controls (only 4 of 7 became SHIV-infected; median day 4) (p=0.02, Wilcoxon rank sum). Accounting for a 7-10 day viral eclipse period, TV-CT-coinfected macaques were then SHIV-infected earlier in the menstrual cycle, compared to controls.
Conclusions: Relative to the menstrual cycle, TV-CT-coinfected macaques exhibited different SHIV infection timelines, compared to controls. Control animals had similar infection timelines as macaques in previously reported studies in which increased SHIV susceptibility was observed in the late-luteal phase. TV-CT coinfection may negate innate defenses present earlier in the menstrual cycle, creating an immune or tissue milieu that is naturally more permissive to (S)HIV, and possibly other STDs, throughout the menstrual cycle.