Pharmacokinetics and Pharmacodynamics of Tenofovir Reduced-Glycerin 1% Gel in the Rectal and Vaginal Compartments in Women: A Cross-Compartmental Study With Directly Observed Dosing

J Acquir Immune Defic Syndr. 2018 Jun 1;78(2):175-182. doi: 10.1097/QAI.0000000000001655.


Background: Evidence is lacking regarding whether vaginal pre-exposure prophylaxis with topical tenofovir (TFV) reduces the risk of rectal HIV acquisition.

Setting: Bronx, NY.

Methods: MTN-014 was a phase 1, cross-over, randomized sequence trial comparing the cross-compartment pharmacokinetics and pharmacodynamics of daily TFV reduced-glycerin 1% gel after 14 days each of rectal and vaginal application, with directly observed dosing and a 6-week washout period between phases.

Results: Fourteen HIV-uninfected women enrolled; 91% of doses were observed and 13 women completed all study procedures. TFV and TFV diphosphate (TFV-DP) were detected in most samples collected from the dosing compartment. After vaginal dosing, TFV was detected in 10/14 samples of rectal fluid (RF) (median 4.4 ng/sponge) and 1/13 rectal tissue samples (0.2 ng/mg); TFV-DP was detected in 2/13 rectal tissue samples at 59.8 and 76.5 fmol/mg. After rectal dosing, TFV was detected in 9/14 samples of vaginal fluid (median 1.1 ng/swab) and in 6/14 vaginal tissue samples (median below limit of quantification); TFV-DP was detected in 3/14 vaginal tissue samples at 17.3, 87.6, and 77.1 fmol/mg. Neither cervicovaginal lavage fluid nor RF collected 24 hours after rectal or vaginal dosing resulted in a statistically significant suppression of viral replication.

Conclusions: In this study of 14 days each of vaginal and rectal application of TFV reduced-glycerin 1% gel, we found only a small degree of cross-compartment distribution of TFV in RF and vaginal fluids and no pharmacodynamic activity in ex vivo testing. Although high TFV concentrations in the dosing compartment may be protective, low cross-compartment tissue concentrations are not likely to be protective.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacokinetics
  • Administration, Rectal
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacokinetics*
  • Body Fluids
  • Dose-Response Relationship, Drug
  • Female
  • Gels
  • Glycerol / metabolism*
  • HIV Infections / prevention & control*
  • HIV Infections / virology
  • Humans
  • Middle Aged
  • Organophosphates / pharmacokinetics
  • Pre-Exposure Prophylaxis
  • Rectum / drug effects*
  • Tenofovir / administration & dosage*
  • Tenofovir / pharmacokinetics*
  • Treatment Outcome
  • Vagina / drug effects*
  • Vaginal Creams, Foams, and Jellies / administration & dosage
  • Vaginal Creams, Foams, and Jellies / pharmacokinetics
  • Virus Replication / drug effects
  • Young Adult


  • Anti-HIV Agents
  • Gels
  • Organophosphates
  • Vaginal Creams, Foams, and Jellies
  • tenofovir diphosphate
  • Tenofovir
  • Adenine
  • Glycerol