PHILADELPHIA – A microbicide gel intended to prevent HIV infection in women, called PRO 2000 (0.5% dose), was 30% effective, according to results from a clinical trial conducted at the University of Pennsylvania School of Medicine and six trial sites in Africa. The results of the study, known as HPTN 035, were presented today at the international Conference on Retroviruses and Opportunistic Infections in Montreal, Canada. This is the first human clinical study to suggest that a microbicide gel may prevent male-to-female sexual transmission of HIV infection.
Based on the study’s final analysis, 194 HIV infections occurred during the study. Of this total, 36 infections occurred among participants who used PRO 2000, 54 infections occurred among participants who used BufferGel, 51 infections occurred among participants who used placebo gel, and 53 infections occurred among participants who used no gel. Using these data as a basis for determining the effectiveness of the two candidate microbicides, the researchers found that BufferGel had no effect on HIV prevention, but PRO 2000 had a 30 percent level of effectiveness. That is, the rate of HIV seroconversion was 30% lower in the women who used PRO 2000 as compared to the women who used the placebo gel or no gel. Both PRO 2000 and BufferGel were found to be safe.
“A safe and effective microbicide could protect women and substantially reduce new HIV infections here in Philadelphia and globally,” says Lisa A. Maslankowski, M.D., principal investigator of HPTN 035 and lead researcher of the HIV/AIDS Prevention Research Division's Microbicide Trials Unit at the University of Pennsylvania School of Medicine. “While further clinical research is needed to more definitively determine the gel’s effectiveness, the results of this study represent a significant step forward for HIV prevention research.”
1.6 million HIV infections could be averted over 3 years if a microbicide with 40% effectiveness were used in 73 low income countries, according to mathematical modeling conducted by the London School of Hygiene and Tropical Medicine.
Currently, women comprise half of all people worldwide living with HIV. In the United States, there are an estimated 1,039,000 to 1,185,000 persons living with HIV/AIDS and a quarter of the 35,314 people newly diagnosed with HIV/AIDS in 2006 were women according to the most recent figures from the U.S. Centers for Disease Control and Prevention. In sub-Saharan Africa, women represent nearly 60 percent of adults living with HIV, and in several southern African countries young women are at least three times more likely to be HIV-positive than young men.
In most cases, women become infected with HIV through sexual intercourse with an infected male partner. Although no microbicides are approved or available for use, an effective product could provide women with an HIV prevention method they initiate. This would be particularly helpful in situations where it is difficult or impossible for women to negotiate condom use with their male partners to prevent HIV transmission.
About the Study
HPTN 035 was conducted between February 2005 and September 2008 and involved 3,099 women at six sites in Africa and one in the United States. PENN Medicine enrolled 200 women in Philadelphia. Women enrolled in Philadelphia ranged from 18 to 59 years old with a mean age of 35.5 years. Seventy-five percent of the women in the Penn cohort were African American, 19% were White, 0.5% were Native American, 6.5% self-identified as multi-racial or other. Six percent were Hispanic. Eighty-six percent were unmarried.
The clinical trial tested two microbicide gels for safety and their ability to prevent HIV infection: PRO 2000 (0.5% dose), developed by Indevus Pharmaceuticals, Inc., in Lexington, Massachusetts, U.S.A., and BufferGel, developed by ReProtect Inc., in Baltimore, Maryland, U.S.A. In earlier laboratory and animal testing, PRO 2000 demonstrated a protective effect against HIV and other sexually transmitted infections by inhibiting cellular entry. BufferGel was known to boost the natural acidity of the vagina in the presence of seminal fluid, which can help to inactivate HIV and other pathogens.
Women in the study were randomly assigned in equal numbers to one of four groups: those who used BufferGel prior to engaging in sexual intercourse; those who used PRO 2000 before each sex act; those who used placebo gel (with no active ingredient) prior to sexual activity; and those who used no gel. Women took part in the study for an average of 20 months and were evaluated monthly. All participants received detailed information about the possible risks and benefits of trial participation prior to enrollment and were monitored closely throughout the study. In addition, all participants were counseled on safe sex practices, provided with condoms, and tested and treated for sexually transmitted infections throughout the study.
The HPTN 035 study successfully retained a majority of its enrollees, with 94 percent completing participation. Throughout the study, participants reported regular use of the investigational gels (81 percent of sex acts) and nearly all (99 percent) said they would use the products if approved for HIV prevention. Condom usage was also high throughout the course of the trial (72 percent).
“Without the dedication and commitment of the women who took part in the study, this advancement in the fight against HIV would not have been possible,” says Dr. Maslankowski.
Study participants are being informed of the findings and counseled on the continued need to follow safe sex practices in order to avoid possible HIV exposure.
The study as a whole was led by protocol chair Salim S. Abdool Karim, MBChB, Ph.D., from the University of KwaZulu-Natal in Durban, South Africa and director of the Center for the AIDS Program of Research in South Africa. It was conducted by a team of American and African researchers working in the Microbicide Trials Network (MTN), an HIV/AIDS clinical trials network established and funded in 2006 by the U.S. National Institute of Allergy and Infectious Diseases (NIAID) with co-funding by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the National Institutes of Health. Prior to the establishment of the MTN in 2006, the study was led by the NIAID-funded HIV Prevention Trials Network (HPTN), from which the study gets its name.
“While the results of the HPTN 035 study are not conclusive, they provide a glimmer of hope to millions of women at risk for HIV, especially young women in Africa,” adds Dr. Abdool Karim. “These findings provide the first signal that a microbicide gel may be able to protect women from HIV infection.”
PRO 2000 (0.5% dose) is being studied in a separate clinical trial in Africa, sponsored by the Medical Research Council (MRC) and the Department for International Development of the United Kingdom, to determine the efficacy of preventing HIV infection among women. That study is set to conclude in late 2009.
Dr. Maslankowski has no financial ties to Indevus Pharmaceuticals, Inc. or ReProtect, Inc. The HPTN 035 study was funded by NIAID. Indevus Pharmaceuticals, Inc. provided PRO 2000 and ReProtect, Inc. provided BufferGel. The U.S. Agency for International Development (USAID) provided funding to manufacture BufferGel for the study.
For more information about the HPTN 035 clinical study, visit:
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