Hormonal Contraceptives Differentially Suppress TFV and TAF Inhibition of HIV Infection and TFV-DP in Blood and Genital Tract CD4+ T cells

Sci Rep. 2017 Dec 18;7(1):17697. doi: 10.1038/s41598-017-18078-3.

Abstract

HIV prevention research is focused on combining antiretrovirals (ARV) and progestin contraceptives to prevent HIV infection and pregnancy. The possibility that progestins compromise ARV anti-HIV activity prompted us to evaluate the effects of progestins on tenofovir (TFV) and TFV-alafenamide (TAF) on HIV infection and intracellular TFV-diphosphate (TFV-DP) concentrations in blood and genital CD4+ T cells. Following incubation of blood CD4+ T cells with TFV or TAF, Medroxyprogesterone acetate (MPA), but not Levonorgestrel, Norethisterone or progesterone, suppressed the anti-HIV effect of TFV by reducing intracellular TFV-DP, but had no effect on TAF inhibition of infection or TFV-DP. In contrast, with genital CD4+ T cells, MPA suppressed TAF inhibition of HIV infection and lowered of TFV-DP concentrations without affecting TFV protection. These findings demonstrate that MPA selectively compromises TFV and TAF protection in blood and genital CD4+ T cells and suggests that MPA may decrease ARV protection in individuals who use ARV intermittently for prevention.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Adult
  • Anti-HIV Agents / pharmacology
  • Anti-Retroviral Agents / therapeutic use
  • CD4-Positive T-Lymphocytes / drug effects*
  • Cells, Cultured
  • Contraceptive Agents / pharmacology
  • Contraceptives, Oral, Hormonal / adverse effects
  • Contraceptives, Oral, Hormonal / pharmacology*
  • Female
  • Genitalia, Female / drug effects
  • HIV Infections / drug therapy
  • HIV Infections / prevention & control*
  • HIV-1 / drug effects
  • Humans
  • Middle Aged
  • Organophosphates / pharmacology
  • Progestins / antagonists & inhibitors
  • Progestins / physiology
  • Tenofovir / pharmacology
  • Tenofovir / therapeutic use

Substances

  • Anti-HIV Agents
  • Anti-Retroviral Agents
  • Contraceptive Agents
  • Contraceptives, Oral, Hormonal
  • Organophosphates
  • Progestins
  • tenofovir diphosphate
  • Tenofovir
  • GS-7340
  • Adenine