International trial of two microbicides begins

A large, multisite trial designed to examine the safety and preliminary effectiveness of two candidate topical microbicides to prevent HIV infection has opened to volunteer enrollment. The trial, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, represents a partnership among various research institutions in Africa and the United States. Although no licensed microbicides are available to the public currently, scientists hope these agents–designed to be applied to the surface of the vagina to prevent sexually transmitted infections (STIs)–will one day be a key tool in the fight against HIV/AIDS.

Women make up nearly half of all people living with HIV worldwide. “The majority of new cases of HIV infection in women result from heterosexual intercourse, but women may not always be able to insist that their male partners use measures to prevent HIV transmission,” notes NIAID Director Anthony S. Fauci, M.D. “If effective, microbicides would be a valuable woman-controlled means of slowing the pace of the HIV/AIDS epidemic,” Dr. Fauci adds.

The first volunteers were enrolled this week at sites in Durban, South Africa, and at the University of Pennsylvania in Philadelphia. Enrollment will begin shortly at sites in four additional African countries–Malawi, Tanzania, Zimbabwe and Zambia. Approximately 3,220 women will be enrolled in the trial, which is expected to last approximately 30 months.

“This is the first microbicide safety and effectiveness trial of this magnitude to be conducted by NIAID,” says Roberta J. Black, Ph.D., Topical Microbicide Team Leader in NIAID’s Division of AIDS. “It is a critical trial evaluating two topical microbicides with differing mechanisms of action,” she adds.

The microbicides to be tested are PRO 2000 and BufferGel. Produced by Indevus Pharmaceuticals, Lexington, MA, PRO 2000 has shown activity against HIV and other STIs in both laboratory and animal testing. It is believed to act by inhibiting the entry of HIV and other pathogens into body cells. BufferGel, a product of ReProtect, Inc., Baltimore, MD, boosts the natural acidity of the vagina in the presence of seminal fluid that neutralizes the vaginal environment. An acidic environment inactivates HIV as well as other pathogens.

Each woman in the trial will be placed at random into one of four equally sized groups. One group will use BufferGel before each act of sexual intercourse, one group will use PRO 2000, one group will use a placebo gel, and the final group will not use any gel. In addition, all participants will receive condoms and extensive prevention counseling at each clinic visit.

The trial is one of numerous studies conducted through NIH’s HIV Prevention Trials Network (HPTN), which is funded by NIAID, the National Institute of Child Health and Human Development, the National Institute on Drug Abuse and the National Institute of Mental Health. More information about this study (HPTN 035) is available at www.hptn.org/index.htm. The protocol chair of the study is Salim Abdool Karim, MBChB, Ph.D., of the University of KwaZulu-Natal in Durban, South Africa.