MTN-014

Primary Objective

• Compare local and systemic pharmacokinetics (PK) of reduced-glycerin tenofovir 1% gel after 2 weeks of daily rectal use and after 2 weeks of daily vaginal use

Study Summary
MTN-014 was a Phase 1, two-arm, crossover, randomized trial in healthy, HIV-negative, sexually active women aged 21 to 45 (inclusive) years to assess the level of tenofovir in both the rectal and vaginal compartments after the rectal and vaginal application of RG tenofovir 1% gel. Fourteen women were enrolled and randomized to the sequence of vaginal or rectal RG tenofovir 1% gel application for two weeks. Blood, vaginal and rectal samples, including tissue, were collected to assess the PK endpoints at the end of the first period of product use. Following a minimum 6-week washout period, women who initially applied the product vaginally were crossed-over to apply product rectally and vice versa. Secondary objectives of MTN-014 study included safety assessment of RG tenofovir 1% gel after 2 weeks of rectal and after 2 weeks of vaginal use. 

MTN-014 completed follow-up on December 22, 2014. Results were presented at the International AIDS Conference (IAS) (HIV Pathogenesis Treatment and Prevention) held on July 19-22, 2015, in Vancouver, Canada. The primary manuscript, the only paper from this study, was published in Journal of Acquired Immune Deficiency Syndromes on June 1, 2018.

Primary 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. 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.