MTN-001

Primary Objectives

• Compare adherence to and acceptability of three daily regimens of tenofovir (oral, vaginal, and dual use)
• Compare systemic and local pharmacokinetics (PK) among three regimens of tenofovir (oral, vaginal, and dual use) in a subset of participants

Study Summary
MTN-001 was a Phase 2, multi-site, randomized, six-sequence, three-period, open-label crossover study of adherence to and PK of tenofovir disoproxil fumarate (TDF) 300 mg tablet and tenofovir 1% gel. The study population included 18 to 45 years old healthy women who were HIV-uninfected, non-pregnant, sexually active and used adequate contraception. All participants enrolled at the US study sites underwent more intensive specimen collection for PK analysis. In addition to the primary objectives above, the MTN-001 study characterized the differential safety profiles of the three different daily regimens of tenofovir and assessed the level of study product sharing with non-participants. This protocol also investigated factors associated with product adherence and potential variations in sexual activity and male condom use associated with the different regimens. An optional procedure for participants at one site – the BLHC CRS in New York – was the collection of rectal swabs to assess tenofovir levels in the rectum following intravaginal administration of tenofovir 1% gel.

MTN-001 completed follow-up on July 30, 2010. Results were first presented at the 18^th Conference on Retroviruses and Opportunistic Infections (CROI) held on February 27- March 3, 2011, in Boston, MA. The two primary papers were published online in PLoS One in January 2013 and in AIDS and Behavior in February 2012, respectively. A total of seven papers have been published from this study.

Primary Results
All three study regimens (TDF 300 mg tablet, tenofovir 1% gel and a combination of TDF 300 mg tablet and tenofovir 1% gel) were well-tolerated and acceptable. Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03). A statistically significant preference for the oral product was noted (p=0.002); this was largely driven by US sites. Self-reported adherence across sites was high (94%).