New microbicides enter trials in United States

Two potential candidates in the microbicide research pipeline are set to be examined in clinical trials this fall, with research to focus on the safety and acceptability in healthy women and women infected with HIV.

Two agents are scheduled to be studied at the Hope Clinic of the Emory Vaccine Center in Decatur, GA, says Lisa Grohskopf, MD, MPH, a medical epidemiologist with the Atlanta-based Centers for Disease Control and Prevention (CDC), which is sponsoring the research. The agents are UC-781, a nonnucleoside reverse transcriptase inhibitor, and cellulose acetate phthalate, a pharmaceutical excipient used for enteric film coating of tablets and capsules.

UC-781 works by blocking reverse transcriptase, a protein that HIV needs to make more copies of itself, she explains. Cellulose acetate phalate has a less specific form of action; it appears to inactivate the virus, she notes.

The first study, which should begin enrolling this fall, will be a phase I study of the safety and acceptability of UC-781 gel, says Frances Priddy, MD, MPH, associate director at the clinic and assistant professor of medicine at Emory University. Scientists will test the gel in approximately 36 healthy, HIV-negative women and also will test the gel for safety in a smaller number of HIV-infected women, she states.

It is important that the public understands that testing a microbicide in HIV-infected women is not done because scientists believe the agent can cure HIV, Priddy points out. Any microbicide that is licensed for use may be used by a wide variety of women — some of whom are likely to be HIV-infected — so it is important to test for safety in this population as well, she explains.

"Also, we are interested in seeing if use of a microbicide will reduce the amount of HIV virus present in the genital tract of HIV-infected women, which could reduce the rate of HIV transmission to their sexual partners," adds Priddy. This first study will last about 14 days, she says.

UC-781 originally was developed by scientists at Greenwich, CT-based Crompton Corp., a producer and marketer of specialty chemicals and polymer products, to combat pathogenic fungi in crops. Early research indicated that UC-781 demonstrated potential activity against HIV.1 Biosyn of Huntingdon Valley, PA, is pursuing development of the compound as a potential topical microbicide.

The Contraceptive Research and Development Program (CONRAD) in Norfolk, VA, recently concluded a single-center Phase I placebo-controlled randomized study of UC-781 to evaluate the safety and acceptability of daily intravaginal dosing of the product in 48 healthy, abstinent women. Data now are under analysis, according to CONRAD officials.

Researchers at the University of Pittsburgh and Magee-Women’s Research Institute, both in Pittsburgh, also are examining UC-781 as a potential microbicide candidate. The National Institutes of Health awarded a five-year, $8 million grant in 2003 to the university to conduct laboratory and clinical studies of the experimental microbicide.2 Research at Pitt is focusing on:

  • evaluating the microbial activity of UC-781, alone and in combination with other active components, against a variety of strains of HIV;
  • determining the toxicity and efficacy of UC-781 on HIV transmission rates;
  • formulating UC-781 with other active agents to improve potency, effectiveness, and ease of use.3

Scientists at the New York Blood Center in New York City reported in 1999 that cellulose acetate phthalate, a pharmaceutical excipient commonly used in the production of enteric tablets and capsules, displayed antiviral activity against HIV-1 and several herpes viruses.4 Further research indicates the agent may be effective in inactivating HIV-1.5

Female-controlled methods of HIV prevention are needed, as many women and teen-age females do not have the autonomy to require condom use or monogamy from their male partners, says Priddy. This lack of autonomy is especially prevalent in some developing countries, she notes. "As the number of women infected with HIV through heterosexual sex continues to rise, it makes sense to work toward a female-controlled method of HV prevention such as an effective topical microbicide."


1. Borkow G, Barnard J, Nguyen TM, et al. Chemical barriers to human immunodeficiency virus type 1 (HIV-1) infection: Retrovirucidal activity of UC781, a thiocarboxanilide nonnucleoside inhibitor of HIV-1 reverse transcriptase. J Virol 1997; 71:3,023-3,030.

2. Spice B. Pitt gets $8 million grant to study AIDS-blocking gel. Pittsburgh Post-Gazette. Jan. 10, 2003. Accessed at:

3. Baum M. Grant funds research to develop microbicide barrier to HIV. Jan. 9, 2003. Press release. Accessed at: news

4. Neurath AR, Strick N, Li YY, et al. Design of a microbicide’ for prevention of sexually transmitted diseases using inactive’ pharmaceutical excipients. Biologicals 1999; 27:11-21.

5. Neurath AR, Strick N, Li YY, Debnath AK. Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor-binding site on the virus envelope glycoprotein gp120. BMC Infect Dis 2001; 1:17. Epub Sep 25, 2001.