STD Quarterly
Tenofovir eyed as potential microbicide
An experimental anti-HIV tenofovir gel is safe for women to use on a daily basis, according to research conducted by the scientists at the University of Pittsburgh (PA) School of Medicine and the University of Alabama at Birmingham (UAB).1
"In the short term, we think the antiretroviral tenofovir is probably one of the most exciting avenues of research," says Sharon Hillier, PhD, professor and vice chair for faculty affairs and director of reproductive infectious disease research in the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of Pittsburgh School of Medicine. "There's real hope that this drug, either taken as a pill or topically, could help prevent HIV, and in the coming months we will be launching a series of clinical studies that will bring us closer to understanding if this is so."
One of the planned clinical studies is a large Phase IIb trial specifically designed to evaluate the safety and effectiveness of oral and vaginal routes of delivery of the drug, says Hillier, who led the current study. The trial also will help researchers determine which approach women prefer, says Hillier, who serves as principal investigator in the Microbicide Trials Network, a worldwide collaborative clinical trials network funded by the National Institutes of Health.
Will women use gel?
To conduct the currently reported study, scientists enrolled 200 sexually active, HIV-negative women at UAB, Bronx-Lebanon Hospital Center in New York City, and the National AIDS Research Institute in Pune, India. Women ranged in age from 19 to 50, and 64% were married.
Once enrolled, women randomly were assigned to one of four groups: those using tenofovir gel each day; those applying tenofovir gel up to two hours before sex; those using a placebo gel every day; or those applying a placebo gel before sex. Women were assessed at one-month, three-month, and six-month increments. Women received free condoms and HIV risk-reduction counseling, as well as routine testing and treatment for sexually transmitted infections throughout the study.
An analysis of the study results found no differences in liver, blood, and kidney function between the groups of women using either regimen of tenofovir gel and the groups assigned to placebo. There also were no differences in safety measures between the groups using daily gel and those who used the gel with sex. No statistical differences were reported in the development of genital symptoms. No participants acquired HIV during the study.
Most adhered to treatment
Adherence to treatment was similar, according to structured interviews. A majority (80%) of the women instructed to use gel within two hours of having sex said they complied with the regimen. Of the women in the daily-use groups, an average of 83% reported gel use in the past week. The two most cited reasons women gave for not using gel was menstruation (41%) and forgetting to apply it (23%).
Overall, about half (41%) of the women said there was nothing they disliked about using the gel, and 39% said it was easy to use. Some women said use of the gel made sex more pleasurable, notes Craig Hoesley, MD, a co-author of the research and associate professor in the UAB Division of Infectious Diseases. "The gel is safe, too, and well tolerated by HIV-negative women; that's a key message in our findings," he says. "This sets the stage for larger studies to see if tenofovir can prevent HIV infection."
More studies planned
In its pill form, tenofovir is used in one of the most widely used regimens for treating HIV. Oral and topical formulations of the drug were developed by Gilead Sciences of Foster City, CA. Gilead assigned a royalty-free license for the topical gel in December 2006 to the International Partnership for Microbicides of Silver Spring, MD, and CONRAD of Arlington, VA.
The active ingredient in tenofovir gel belongs to a class of antiretroviral drugs known as nucleotide reverse transcriptase inhibitors. Such drugs act against HIV by targeting a key enzyme that HIV needs to copy itself before taking over a host cell.
CONRAD and Family Health International are conducting a study of 1% tenofovir gel in 980 women at two sites in KwaZulu Natal, South Africa. The study is looking at coitally dependent use. Results may be available by 2010.
The Microbicides Trials Network is developing a study that will directly compare a tenofovir gel with oral tenofovir pre-exposure prophylaxis in 4,200 women at 10 sites in South Africa, Malawi, Uganda, Zambia, and Zimbabwe. The study is due to start in late 2008 and may report by 2011.2 "Based on what we have learned, we can proceed with greater confidence on a path that will answer whether tenofovir gel and other gels with HIV-specific compounds will be able to prevent sexual transmission of HIV in women when other approaches have failed to do so," says Hillier.
References
- Hillier SL. Safety and acceptability of daily and coitally dependent use of 1% tenofovir over six months of use. Presented at the Microbicides 2008 Conference. New Delhi, India; February 2008.
- Cairns G. Microbicides 2008: The second generation is on its way. Accessed at www.aidsmap.com.
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