Funding Source and Project Period: DAIDS, NIAID, NIMH, USNIH, U01 AI068633, 6/01/08 – 5/31/10

Key Personnel:
Principal Investigators: Dr. Ian McGowan, Dr. Kenneth Mayer
Co-investigator: Dr. Alex Carballo-Diéguez
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Project Overview:

To date, the majority of microbicide research has focused on the assessment of the safety and effectiveness of vaginal microbicides used for the prevention of HIV transmission via the vaginal compartment. Receptive anal intercourse (RAI) is common among men who have sex with men (MSM) and there is increasing evidence that heterosexual women also practice anal sex. It can therefore be anticipated that once vaginal microbicides are licensed, they will be used in both the vaginal and rectal compartments. As a consequence, there is a need to evaluate both the rectal and vaginal safety profile of candidate microbicides. This clinical trial has been developed to assess the safety and acceptability of tenofovir 1% gel when used rectally in men and women. This trial will complement RMP-02/MTN-006 (Phase 1 Rectal Microbicide Safety and Acceptability Trial of Topically Applied Tenofovir Compared with Oral Tablet) by focusing on accumulating Phase I safety and acceptability data, while providing in its secondary and exploratory objectives the data needed to determine maximum and minimum parameters for a suite of potential rectal safety assays using comparisons of the results from 2% Nonoxynol-9 gel, HEC placebo gel, and no treatment arms. Together these two trials should act synergistically to determine/establish: (1) initial safety of tenofovir 1% gel as a rectal microbicide; (2) acceptability of a vaginally formulated tenofovir gel when used rectally; (3) pharmacokinetic/pharmacodynamic parameters for rectal tenofovir 1% gel use; and (4) further validate the proposed rectal safety suite by establishing maximum (Gynol II®), minimum (HEC placebo), and baseline (no treatment) mucosal responses, while proactively managing participant and clinical site burden.

 

This Phase 1 study will examine the safety and acceptability of tenofovir 1% gel when applied rectally in HIV-uninfected adults (male and female). The study will be conducted with 60 receptive anal intercourse abstinent men and women recruited at three MTN study sites: Alabama Microbicides CRS, Birmingham, AL; Fenway Clinic CRS, Boston, MA; and Pittsburgh CRS, Pittsburgh, PA. The study design consists of a three-arm, randomized, blinded, multi-site, placebo controlled trial comparing tenofovir 1% gel, 2% Nonoxynol-9 gel, and HEC placebo gel (20 participants per group) applied rectally (a single inpatient dose, and once daily outpatient doses for seven days). The primary objective of MTN 007 is to assess the safety of tenofovir 1% gel when administered rectally. The main behavioral objective is to evaluate product acceptability.

 

The behavioral assessment to explore product acceptability and adherence consists of three measures, administered via CASI: 1) the Baseline Behavioral Questionnaire, taken at the Enrollment Visit, which consists of a Web-based self interview to assess participants’ demographics and sexual behavior in the prior three months; 2) the Adherence Questionnaire, using a phone reporting system that will be deployed via Voice over IP technology, completed daily during the seven days of outpatient gel use; and 3) the Product Acceptability Questionnaire, taken at the Final Clinic Visit, which consists of a Web-based self interview.