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Background Depot-medroxyprogesterone acetate ( DMPA) has been associated in some studies with increased HIV susceptibility in women. We used a pigtail macaque model to document the effects of repeated DMPA treatments and their potential contribution to increased SHIV susceptibility. Methods Nine pigtails were administered 2.5, 1.5, or 0.5 mg/kg DMPA in study weeks one and four. Menstrual cycling, vaginal epithelial thickness, and other SHIV susceptibility factors were monitored for a mean of 24 study weeks. Results All DMPA treatments suppressed menstrual cycling and increased vaginal pH. The vaginal epithelium thinned naturally during baseline menstrual cycles (from mean of 351 to 161 μm in late-luteal phase). Following DMPA, the non-nucleated layer was temporarily absent. Two weeks post-second DMPA injection, mean epithelial thickness was 53, 45, and 167 μm for the descending doses, respectively. Conclusions All animals showed temporal vaginal epithelial thinning with loss of the non-nucleated layer, and vaginal pH changes post- DMPA injections. [ABSTRACT FROM AUTHOR]

Background Injectable hormonal contraception may increase women's risk of HIV acquisition and can affect biological risk factors in animal models of HIV. We established, for the first time, a model to investigate whether combined oral contraceptives ( COC) alter SHIV susceptibility in macaques. Methods Seven pigtail macaques were administered a monophasic levonorgestrel ( LNG)/ethinyl estradiol ( EE) COC at 33% or 66% of the human dose for 60 days. Menstrual cycling, vaginal epithelial thickness, and other SHIV susceptibility factors were monitored for a mean of 18 weeks. Results Mean vaginal epithelial thicknesses were 290.8 μm at baseline and 186.2 μm during COC ( P = 0.0141, Mann- Whitney U-test). Vaginal p H decreased from 8.5 during treatment to 6.5 post-treatment (0.0176 two-tailed t-test). Measured microflora was unchanged. Conclusions COC caused thinning of the vaginal epithelium and vaginal p H changes, which may increase SHIV susceptibility. 0.033 mg LNG + .0066 mg EE appeared effective in suppressing ovulation. [ABSTRACT FROM AUTHOR]

Background Long-acting, hormonal contraception may increase HIV risk. Copper intrauterine devices ( IUDs) could serve as non-hormonal alternatives. We pilot a pigtail macaque model for evaluating HIV susceptibility factors during copper IUD use. Methods Frameless and flexible GyneFix® copper IUDs were surgically implanted into three SHIVSF162p3-positive macaques via hysterotomy and monitored for up to 4 months. Four macaques served as non- IUD controls. Results All animals retained the devices without complications. No consistent change in vaginal viral RNA or inflammatory cytokines was seen. Two animals had altered menstrual cycles and experienced marked thinning of vaginal epithelium after IUD insertion. Histological examination of uterine tissue at necropsy revealed endometrial ulceration and lymphocytic inflammation with glandular loss at sites of direct IUD contact. Conclusions Although the need for insertion surgery could limit its usefulness, this model will allow studies on copper IUDs and SHIV shedding, disease progression, and HIV susceptibility factors. [ABSTRACT FROM AUTHOR]