A combined oral contraceptive affects mucosal SHIV susceptibility factors in a pigtail macaque (Macaca nemestrina) model

J Med Primatol. 2015 Apr;44(2):97-107. doi: 10.1111/jmp.12157. Epub 2014 Dec 23.

Abstract

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 pH 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 pH changes, which may increase SHIV susceptibility. 0.033 mg LNG + .0066 mg EE appeared effective in suppressing ovulation.

Keywords: SHIV; contraception; non-human primate (NHP); susceptibility; transmission risk.

Publication types

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

MeSH terms

  • Animals
  • Contraceptives, Oral, Combined / adverse effects
  • Contraceptives, Oral, Combined / pharmacology*
  • Disease Models, Animal
  • Disease Susceptibility / chemically induced*
  • Disease Susceptibility / physiopathology
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Ethinyl Estradiol / adverse effects
  • Ethinyl Estradiol / pharmacology*
  • Female
  • HIV Infections / physiopathology*
  • Levonorgestrel / adverse effects
  • Levonorgestrel / pharmacology*
  • Macaca nemestrina
  • Menstrual Cycle / drug effects
  • Mucous Membrane / drug effects*
  • Simian Acquired Immunodeficiency Syndrome / physiopathology*
  • Simian Immunodeficiency Virus / drug effects
  • Vagina / drug effects

Substances

  • Contraceptives, Oral, Combined
  • Drug Combinations
  • ethinyl estradiol, levonorgestrel drug combination
  • Ethinyl Estradiol
  • Levonorgestrel