"The results of this study may change the way the research community looks at developing safe and effective microbicides," says lead author Kenneth H. Mayer, MD, an infectious disease physician at The Miriam Hospital and professor of medicine and community health at Brown Medical School, both in Providence, RI. "Analyzing the compounds that already have been shown to be successful HIV treatment drugs, and evaluating them for their potential to prevent transmission of infection is an innovative approach that shows great promise."
Published in the Feb. 28 issue of the journal AIDS, currently available online, the multi-site study suggests that as a vaginal gel, tenofovir produced mild or no side effects in both HIV positive and HIV negative women. Tenofovir is the active ingredient in the antiretroviral drug Viread made by Gilead Sciences.
Currently, there is no microbicide available that has been approved for widespread use. The tenofovir study was a safety and product acceptability study and did not evaluate if the microbicide would be effective in preventing the transmission of HIV in women. Expanded safety and effectiveness testing is needed.
"The data will pave the way for further studies that will ultimately evaluate whether the gel protects women from HIV infection," says co-author Lisa A. Maslankowski, MD, medical director of the HIV Prevention Research Division at the University of Pennsylvania School of Medicine. "As the first investigational microbicide to contain an antiretroviral agent, tenofovir gel can prevent HIV from replicating, unlike other microbicides which have been designed to block HIV entry into cells, or have other mechanisms of action."
If HIV cannot replicate, the authors infer, it is unlikely that it will be able to survive in the body long enough to cause infection. Prior research shows that tenofovir, when applied as a vaginal gel in monkeys, can block the transmission of Simian Immunodeficiency Virus (SIV), an animal virus that is very similar to HIV.
Approximately 5 million people will be infected with HIV this year – almost half of them women. Because the majority of new HIV infections occur via heterosexual intercourse, there is a need for new ways to prevent the sexual transmission of HIV. Although condoms can offer protection from HIV, in many societies women's legal and social status is subordinate to men's and they may not be able to negotiate their effective use, the paper states.
"A safe and effective topical microbicide would offer women an HIV prevention method that they could control," Mayer says.
In addition, researchers evaluated a subgroup of women in the study to determine if the active ingredient in tenofovir gel was absorbed into their bloodstream. Approximately half of these women had low tenofovir levels in their plasma at one or more times during the 14-day study. Further evaluation is needed to determine if absorption of tenofovir into the bloodstream could be beneficial in enhancing the gel's effectiveness or could cause adverse long-term side effects.
The study participants included 84 women, 18 to 45 years of age. Of those, 60 were not infected with HIV and 24 were HIV-infected women. All participants used the study product for 14 consecutive days and received frequent safety assessments and pelvic exams during the study at one of four research sites: The Miriam Hospital in Providence, RI; Hospital of the University of Pennsylvania in Philadelphia; Harlem Hospital and Bronx-Lebanon Hospital Center, both in New York.
The most common adverse effects reported by women were mild in nature, mainly itching and increased vaginal discharge. None of the participants experienced significant changes in laboratory tests while using the gel.
Past safety trials of microbicides showed that certain gels caused ulcerations and inflammation in women that could actually facilitate HIV transmission. The favorable findings of the tenofovir gel's Phase I safety and acceptability trial has already led to a larger Phase II safety study in at-risk women due to begin in the spring of 2006.
According to the study, there was a high acceptability rate among participants, as 94 percent of women said they would definitely or probably use the gel if it were available and they wanted protection from HIV transmission.
The study was supported by the HIV Prevention Trials Network (HPTN) and sponsored by: the National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Child Health and Human Development; National Institute on Drug Abuse; and National Institute of Mental Health and Office of AIDS Research, of the National Institutes of Health (NIH), U.S. Department of Health and Human Services. Clinical coordination for the study was conducted by Family Health International (Research Triangle, NC), data analysis was performed at the Fred Hutchinson Cancer Center of the University of Washington in Seattle, and HIV resistance testing and pharmacology studies were performed in laboratories at Johns Hopkins University. The Miriam Hospital participates in the HPTN as part of a clinical trial unit coordinated by Fenway Community Health in Boston. The study was also conducted in conjunction with clinical investigators from Women & Infants' Hospital in Providence, RI.
The Miriam Hospital, established in 1926 in Providence, RI, is a not-for-profit hospital affiliated with Brown Medical School. Nationally recognized as a top hospital in cardiovascular care, The Miriam Hospital (www.miriamhospital.org) offers particular expertise in cardiac catheterization, angioplasty and women's cardiac care. One of 20 designated Center for AIDS Research (CFAR) sites, The Miriam is a leader in the treatment, research and prevention of HIV/AIDS, attracting $17 million of the world's HIV/AIDS research dollars. The Miriam Hospital has been awarded Magnet Recognition for Excellence in Nursing Services twice and is committed to excellence in patient care, research and medical education. The Miriam is a founding member of the Lifespan health system.
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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