N-9 film study a blow for microbicide research
Studies continue, but enthusiasm dampened
In a setback for the development of a female microbicide for HIV, a two-year study of Cameroon sex workers has shown that the most common vaginal spermicide did not protect women from acquiring the virus or other sexually transmitted diseases. Other spermicide studies are continuing, however, and researchers are not ready to remove nonoxynol-9 from the microbicide armamentarium.
"I am disappointed for women in that we could not demonstrate that another product in their arsenal against HIV would be protective," says Willard Cates, MD, MPH, senior vice president of biomedical affairs for Durham, NC-based Family Health International, a co-sponsor of the trial. "We must accelerate research dedicated to finding new methods for women at risk of HIV and other STDs."
Large study of its kind
Family Health International collaborated with the Cameroon Ministry of Public Health to conduct the study, which was designed to assess whether a spermicidal film containing nonoxynol-9 (N-9) used in conjunction with condoms offered protection against HIV, gonorrhea, or chlamydia. The study is the most thorough examination to date involving an N-9 spermicide and the role spermicides play in protecting women against STDs. An earlier, smaller N-9 study had suggested that N-9 may reduce the risk of bacterial STD infections, but was inconclusive about whether N-9 prevents HIV infections.1
In 1992 a randomized controlled trial of an N-9 contraceptive sponge used by sex workers in Nairobi, Kenya, concluded that the product didn’t protect women against HIV. The sponge was linked to a three-fold increase in incidence of genital ulcers and a higher rate of HIV infection.2 Many researchers believed the study’s design was flawed, and the Cameroon trial was launched to help clarify N-9’s protective benefits.
The results come four months after a joint meeting of U.S. Food and Drug Administration advisory committees, which recommended that the agency approve N-9 as prophylaxis for gonorrhea and chlamydia based on data showing that N-9 provided a small but measurable impact on those infections. The Cameroon study may affect the FDA’s decision on whether to allow such labeling for N-9, considering that the study showed no protective benefit against either of those STDs.
"This finding raises doubts about the additional benefit from using N-9 film as a prophylactic against STDs with condoms," Cates says. However, he tells AIDS Alert that "while enthusiasm for N-9 has been dampened, it has not been eliminated." Several trials using different formulations and dosages of N-9 are under way, including an N-9 gel formulation called Advantage 24. Should those trials reflect the Cameroon findings, the need for future research of N-9 as a microbicide would be questioned, he adds.
Officials for the Centers for Disease Control and Prevention in Atlanta say the study results would not affect its current recommendations for N-9, which state that the spermicide should be used with condoms.
The Cameroon study involved 1,292 sex workers who volunteered at clinics to take part in the study between March 1995 and December 1996. To be eligible, the women could not be infected with HIV at the time they entered the study. Of the eligible volunteers, 478 who were provided a contraceptive film containing N-9 and 463 who were provided a placebo film that did not contain a spermicide completed the study.
Each woman who volunteered to participate in the study received counseling to discourage her from continuing to work as a sex worker, i.e., as a prostitute, an activity that places one at great risk of acquiring HIV or other STD infections.
Volunteer participants who remained at risk were given condoms and urged to use them with every act of intercourse. They received a new supply of condoms frequently, and were examined monthly and treated for infections.
"The Cameroonian study staff strongly urged volunteers to practice safer sex," Cates says. Volunteers from the cities of Yaounda and Douala received thorough counseling and were asked to return monthly for medical attention, which FHI believes significantly reduced the risks they otherwise would have faced. "Study participants were helped to adopt protective behaviors, which reduced their rate of infection by more than 50 percent," Cates says.
For the women completing the study, 147,996 acts of sexual intercourse in the group using N-9 film and condoms were compared with 146,942 acts in the group provided with the placebo film and condoms. The rate of HIV transmission was nearly the same for both groups. For every 100 women using N-9 film and condoms for one year (100 woman-years), 6.7 became infected with HIV, compared with 6.6 HIV infections using the placebo film and condoms.
The comparable rates for gonorrhea infections were 33.3 infections for N-9 and condoms to 31.1 for placebo film and condoms per 100 woman-years. Infection rates for chlamydia were 20.6 for N-9 and condoms and 22.2 for placebo film and condoms per 100 woman-years.
Researchers have been concerned about whether frequent use of N-9 may increase the risk of STD infections, because frequent use of the chemical may cause sores that could enhance transmission. Women in the study reported using the film more frequently than do most women who use N-9. This study did not show any increased risk of HIV or other STD infections from using N-9 film, although genital lesions (sores) did occur slightly more often among women who used N-9. There were 42.2 lesions per 100 woman-years among women using N-9 and condoms, compared with 33.5 lesions among women using the placebo film and condoms.
While the study was a setback for N-9 research, it showed that in a trial setting in which women were provided monthly STD checkup and safe-sex messages, condom use increased significantly.
"It shows that given the right commitment and resources of public health personnel, you can take populations in which condom use had been very low and raise it substantially," Cates says.