Analysis of putative mucosal SHIV susceptibility factors during repeated DMPA treatments in pigtail macaques

Abstract

All animals showed temporal vaginal epithelial thinning with loss of the non-nucleated layer, and vaginal pH changes post-DMPA injections.

A Depot Medroxyprogesterone Acetate Dose That Models Human Use and Its Effect on Vaginal SHIV Acquisition Risk

“…We determined resulting blood MPA levels over time, and their effectiveness in suppressing ovulation, their ability to induce thinning of the vaginal epithelium, and their effects on other putative HIV susceptibility factors. We showed that a low, monthly DMPA dose of 1.5 mg/kg can achieve suppression of ovulation over two months 18 , while it also achieves constantly detectable MPA levels, and is associated with significant vaginal epithelial thinning. Other slightly lower or higher doses were also associated with changes in these parameters 16-18 .…”

“…We showed that a low, monthly DMPA dose of 1.5 mg/kg can achieve suppression of ovulation over two months 18 , while it also achieves constantly detectable MPA levels, and is associated with significant vaginal epithelial thinning. Other slightly lower or higher doses were also associated with changes in these parameters 16-18 . In summary, we selected 1.5 kg/mg DMPA given monthly for our current study.…”

“…We purchased Depo-Provera ® from Pfizer (New York, NY) and injected suspensions of 1.5 mg/kg DMPA into the gluteal muscle every 28 days as described 18 . Menstrual cycling was monitored by visual observation and plasma progesterone 18 .…”

“…Menstrual cycling was monitored by visual observation and plasma progesterone 18 . Visual observations were recorded on every weekday throughout, and included menstrual blood and perineal tumescence (“sex skin swelling”, documented in 23 ).…”

“…In particular, after intramuscular DMPA injection of comparable doses in macaques, MPA appearance in blood peaks faster and at higher levels than in humans, but it also declines faster and disappears within one month, while it remains detectable for much longer in humans 15 . In earlier work by us and our colleagues 16-18 , various DMPA doses were tested in pigtail macaques (1, 3, 15, 30 mg per macaque, and 0.5, 1.5, and 2.5 mg/kg of body weight). We determined resulting blood MPA levels over time, and their effectiveness in suppressing ovulation, their ability to induce thinning of the vaginal epithelium, and their effects on other putative HIV susceptibility factors.…”