Tenofovir/FTC gel protects female monkeys from SHIV
Mark Mascolini for NATAP.org
Vaginal microbicide research in humans took a recent setback with reports that two products did not protect women from HIV infection. But neither of those microbicides (Carraguard and cellulose sulfate) used antiretroviral agents to ward off HIV.
Urvi Parikh and colleagues at the US Centers for Disease Control (CDC) and Emory University randomized 14 female pigtail macaques to three study groups: 2 received no gel, 6 received a placebo gel (hydroxyethyl cellulose only), and 6 got the tenofovir/FTC gel (5% FTC plus 1% tenofovir, which is equivalent to one Truvada dose, in 2% hydroxyethyl cellulose). 
The tenofovir/FTC gel was clear, odorless, viscous, and stable at 37 degrees Celsius for 6 months. Technicians applied the gels vaginally 30 minutes before challenging the monkeys with SHIV, a simian immunodeficiency virus with an HIV coat, at a dose of about 1,160,000 RNA copies. After exposure the investigators used blood tests and polymerase chain reaction to search for SHIV in plasma. The challenges occurred twice weekly for 10 weeks.
Both monkeys who got no gel and 5 of the 6 who got the placebo gel became infected after a median of 3.5 challenges (range 2 to 11). All 6 pigtails treated with tenofovir/FTC before SHIV exposure remained free of infection after 20 challenges (p < 0.005 versus control groups). The CDC team could detect no viral RNA, no proviral DNA, and no viral antibody in any of the 6 tenofovir/FTC-treated animals.
Parikh and coworkers detected low levels of FTC (median 67 ng/mL) and tenofovir (median 22 ng/mL) in plasma samples 30 minutes after vaginal application. Those findings, the investigators proposed, suggest “rapid drug absorption with relatively higher levels of drug remaining in vaginal tissue.”
Ongoing trials are testing oral tenofovir/FTC (Truvada) as pre-exposure prophylaxis in humans, and a separate study at this workshop showed that oral tenofovir/FTC partially protected male monkeys from rectal SIV exposure.  An earlier study of 1% tenofovir without FTC applied rectally in a single high dose found only a 60% protection rate.  Double therapy clearly did better in this vaginal trial, but Charles Boucher (Erasmus University, Rotterdam) worried about the wisdom of developing drugs for both prevention and treatment because acquired resistance could compromise use of those and other drugs.
A vaginal tenofovir/FTC gel has yet to be tested in humans.
- Parikh UM, Sharma S, Cong M, et al. Complete protection against repeated vaginal SHIV exposures in macaques by a combination emtricitabine and tenofovir topical gel. 3rd International Workshop on HIV Transmission: Principles of Intervention. 31 July -2 August 2008, Mexico City. Abstract 41.
- Garcia-Lerma J, Cong M, Masciotra S, et al. Intermittent pre-exposure prophylaxis (PREP) with oral Truvada protects macaques against repeated rectal SHIV exposures. 3rd International Workshop on HIV Transmission: Principles of Intervention. 31 July -2 August 2008, Mexico City. Abstract 40.
- Cranage M, Sharpe S, Cope A, et al. Pre-exposure prophylaxis in macaques against rectal SIV challenge by mucosally applied PMPA: potential for complementation of microbicide and vaccination strategies. 14th Conference on Retroviruses and Opportunistic Infections. February 25-28, 2007. Los Angeles. Abstract 29.