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

J Med Primatol. 2015 Oct;44(5):286-95. doi: 10.1111/jmp.12188. Epub 2015 Aug 4.

Abstract

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.

Keywords: contraception; non-human primates; transmission risk.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Contraceptive Agents, Female / administration & dosage*
  • Disease Models, Animal
  • Disease Susceptibility / virology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Macaca nemestrina*
  • Medroxyprogesterone Acetate / administration & dosage*
  • Menstrual Cycle / drug effects
  • Mucous Membrane / drug effects
  • Progesterone / metabolism
  • Simian Acquired Immunodeficiency Syndrome / virology*
  • Simian Immunodeficiency Virus / physiology*
  • Vagina / anatomy & histology
  • Vagina / drug effects*

Substances

  • Contraceptive Agents, Female
  • Progesterone
  • Medroxyprogesterone Acetate