A Phase III HIV prevention trial began enrolling this week 3,220 women, representing one of the largest studies of a microbicide ever conducted by the National Institute of Allergy and Infectious Diseases.
But the enrollment number is small, considering the magnitude of the problem. HIV infects about 4.8 million people a year - or 14,000 a day, according to NIAID statistics. And about two-thirds of the 37.8 million people worldwide living with HIV/AIDS are in sub-Saharan Africa.
That's why the NIAID started the pivotal trial of topical vaginal microbicides, one of which is PRO 2000, being developed by Lexington, Mass.-based Indevus Pharmaceuticals Inc. for the prevention of HIV infection in women. The product is believed to act by inhibiting the entry of HIV and other pathogens into body cells.
"We've formulated it basically as a vaginal gel that is designed to be applied by women within an hour [before] initiating sexual intercourse," said William Boni, Indevus' vice president of corporate communications. "The hope is that the gel will basically neutralize the virus when it's introduced into the vagina and protect the woman from infection."
Likewise, the gel could prevent an infected woman from transmitting HIV to an uninfected man.
Since nearly half of all HIV-infected people worldwide are women, researchers believe a vaginal microbicide might be an important agent in slowing the spread of HIV and AIDS. Most new cases of HIV infection that occur in women come from heterosexual intercourse. While condoms can prevent infection, a vaginal microbicide would empower more women to protect themselves.
"Condoms are controlled by men and many women can't negotiate condom use with their male partners," Boni told BioWorld Today. "So this is a potentially alternative technology that can be controlled or initiated by women."
In addition to HIV, a vaginal microbicide might protect people from other sexually transmitted diseases, including gonorrhea, herpes and Chlamydia, Boni said.
The NIAID already has begun enrolling volunteers at sites in Durban, South Africa, and in Philadelphia at the University of Pennsylvania. Enrollment will expand to eight more sites in the following countries: Malawi, South Africa, Tanzania, Zambia and Zimbabwe.
The women will be randomized into four equal groups. Prior to sexual intercourse, one group will use PRO 2000, another group will use a second microbicide, a third group will use a placebo gel and a fourth group will not use any gel. All of the women will receive condoms and prevention counseling at each clinic visit.
Women eligible for the trial live in areas of high HIV prevalence. The study will not track whether the male partners are infected with the virus, but it will test the women for HIV infection on a quarterly basis.
"It's not known whether the products will be effective or not, so ethically, it's a reasonable design," Boni said.
The other microbicide used in the trial is BufferGel, developed by Baltimore-based ReProtect Inc. BufferGel boosts the natural acidity of the vagina in the presence of seminal fluid. An acidic environment inactivates HIV and other pathogens.
"PRO 2000, in essence, attacks the virus and prevents it from infecting the patient," Boni said, "while the other company's product is designed to keep the vaginal ph low and prevent infection that way."
The trial will last about 30 months and an independent Data Safety Monitoring Board will conduct an interim analysis. The NIAID study is being conducted in partnership with various research institutions in Africa and the U.S.
PRO 2000 also will be part of the Microbicides Development Programme (MDP) started in the UK. The program will launch a Phase III trial of PRO 2000 this year in at least 12,000 African women. That project is funded by a £16 million (US$28.6 million) grant from the UK Department for International Development. It is a partnership administered by the Medical Research Council Clinical Trials Unit and Imperial College in London.
"PRO 2000 is the only microbicide to be included in both of those trials," said Al Profy, Indevus' vice president of preclinical development and the program leader for PRO 2000. "The performance of PRO 2000 to date in both animal testing and human testing has led the powers-to-be in the microbicide development world to focus on this as one of the most promising candidates out there."
Earlier clinical studies of PRO 2000 have shown a promising safety and acceptability profile for the drug. They were sponsored by government agencies and research organizations in the U.S., Europe, Africa and India.
Boni said trial results from both the NIAID study and the MDP study should support a regulatory filing in the U.S.
"There's been some mathematical modeling," Boni said, "that even a partially protective product like this could potentially avert millions of HIV infections over a period of a few years."
Since the first AIDS cases were identified in 1981, more than 20 million people have died. In 2003, about 1,700 children under age 15, and 6,000 young people aged 15 to 24, contracted HIV each day, the NIAID said.
Aside from PRO 2000, Indevus markets Sanctura for overactive bladder and it has several compounds in clinical development, including pagoclone for stuttering, aminocandin for systemic fungal infections and IP 751 for pain and inflammatory disorders such as interstitial cystitis.
The company's stock (NASDAQ:IDEV) dropped 5 cents Friday to close at $4.11.