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Multiple clinical trials have evaluated the safety and effectiveness of TFV for the prevention of HIV acquisition in vaginal gel and in oral tablet formulations.  These clinical trials support the favorable safety profile and tolerability of TFV in general and specifically in vaginal and oral delivery formulations. The development of an extended duration intravaginal ring (IVR) may allow less frequent IVR replacements (e.g., quarterly basis instead of monthly basis) that may further reduce patient and provider burden, streamline follow-up, and improve adherence. Such a delivery mechanism could overcome the adherence and efficacy issues observed with the vaginal gel formulation of TFV and challenges with daily dosing of oral TDF/FTC, thus providing a viable vaginal delivery complement to the oral tablet.

MTN-038 was a Phase 1, two-arm, multi-site, randomized (2:1), placebo-controlled trial to evaluate the safety and PK of a 90-day TFV IVR. The study enrolled 49 healthy, HIV-uninfected women aged 18-45. Participants were randomized (2:1) to TFV IVR or placebo and used the assigned IVR for approximately 90 days. MTN-038 evaluated TFV and TFV-DP levels in plasma, cervicovaginal fluid (CVF), rectal fluid, and cervical tissue during approximately 91 days of continuous use of a single ring containing 1.4 g TFV. PK data will help determine the concentration-time profile using pooled data across all participants. The study design includes frequent collection of corresponding blood, rectal and CVF samples following the insertion of a TFV IVR to allow for the detection of drug release from the ring. PK parameters of TFV will be calculated for blood plasma, CVF, rectal fluid, and cervical tissue. It is hypothesized that plasma, CVF, and rectal fluid TFV levels and cervical tissue TFV and TFV-DP levels will be measurable in all participants, and that continuous exposure to TFV due to sustained release from the 1.4 g TFV IVR for 91 days will be safe.

The study completed follow-up on September 25, 2019. The primary manuscript is currently in development.

Protocol Chair(s)
Liu, Albert (Protocol Chair)
Protocol Title
A Phase 1, Randomized, Pharmacokinetic and Safety Study of a 90 Day Intravaginal Ring Containing Tenofovir
DAIDS Protocol ID
38460
Status
Closed to Follow Up
Formulation
Vaginal Ring
Drug
Placebo
Tenofovir   
Study Focus/Product Administration
Vaginal
Study Type
Behavioral
Pharmacokinetics
Safety
Study Phase
Phase I  
Countries
United States
Population
Transgender men
Women (cisgender women, non‐transgender women)
Funder(s)
Division of AIDS, US National Institute of Allergy and Infectious Diseases
US Eunice Kennedy Shriver National Institute of Child Health and Human Development
US National Institute of Mental Health
US National Institutes of Health
Sponsor(s)
DAIDS