Microbicides may increase risk of contracting HIV
Unfavorable results of trial considered setback
The spermicide nonoxynol-9 is ineffective against HIV and may even increase the risk of transmission, according to results of a UNAIDS-sponsored study released at the XIII International AIDS Conference in Durban, South Africa.
The findings of the triple-blind multicenter trial are considered a setback in microbicide research, which until now has received scant support from the private sector and is largely funded by development agencies and nongovernmental organizations.
Microbicides are chemical substances — in the form of gels, creams, suppositories, or films — that kill viruses and bacteria when applied vaginally or rectally before sexual intercourse.
Trial co-coordinator Lut van Damme, MD, MSc, of the Institute of Tropical Medicine in Antwerp, Belgium, said all of the women enrolled in the trial had received intensive condom counseling, free treatment for all sexually transmitted diseases, and regular checkups. Commercial sex workers in Benin, Cote de Ivoire, South Africa, and Thailand were chosen at random from a pool of volunteers who were informed of the risks and who agreed in writing to take part in the tests.
Van Damme said the main objective of the study was to ascertain whether there was a statistically significant difference in the incidence of HIV infection between the two groups of women.
Nonoxynol-9, which is marketed in the United States and China under the trade name Advantage S, is a spermicidal agent used in contraceptive spermicide products and as a complementary component in the lubricant of barrier methods of contraception, such as the male condom.
"We wanted to assess the efficacy of the gel, the long-term safety of its use, and its impact on transmission of HIV to women during sexual intercourse," said Van Damme.
Scientists issue warning to users of product
In the first analysis of the results of seroconversion and HIV incidence among the 990 women who took part in the trials, the researchers found that there was a 15% incidence in the nonoxynol-9 group, compared with 10% in the placebo group, said Van Damme. Women using nonoxynol-9 also exhibited more lesions than those in the placebo group.
"We were dismayed to find out that the group of women using nonoxynol-9 had a higher rate of HIV infection than the group using a placebo," said Joseph Perriens, MD, PhD, who heads the UNAIDS microbicide effort.
The active group had 59 infections, while the placebo group had 41. "This is a significant difference," he explained. "With the incidence of HIV infection in both groups in this study lower than that seen in the untreated population from which volunteers were recruited, it is clear that the rate of infection was greater with the nonoxynol-9 gel compared to its placebo control preparation."
He issued a warning to women at high risk of HIV infection to not use the product because the bulk of evidence suggested that it was either ineffective or harmful as an anti-HIV agent.
Despite the setback, Perriens called for renewed effort and continued commitment to microbicide research. "We have lost one battle, but we have a war ahead of us," he said. "And we think it can be won."
Perriens announced that UNAIDS would call for an acceleration of the introduction of new and more promising microbicide candidates in large-scale phase III trials. Three more products are currently in advanced safety testing and could be available for inclusion in combined safety/efficacy evaluation within months. The safety testing of 10 additional products, including two antiretrovirals, also should be accelerated, he recommended.
Some of those products work by irreversibly inactivating HIV by perforating or disintegrating the virus’s outer membrane. Others block the virus’s attachment to receptors on the cell surface or prevent its replication within the cell by inhibiting the action of reverse transcriptase, an enzyme needed by the virus to establish itself within the cells it infects. Laboratory studies have shown all of those approaches to be highly effective against HIV. Many also are active against sexually transmitted disease pathogens such as Neisseria gonorrhea, Chlamydia trachomatis, and the virus responsible for genital herpes.
Alan Stone, MD, chairman of the International Working Group on Microbicides in London, said considerable resources need to be mobilized to develop microbicides. While 10 public agencies currently are members of the International Working Group, research efforts have been hampered by a lack of funding, leaving many promising leads stuck in the pipeline.
The role of the International Working Group is to facilitate the development and approval of microbicides, which need to be safe as well as effective, affordable, and acceptable to the user.
Adding weight to Perriens’ claim that this type of research is largely underfunded, Perriens said the U.S. government has invested $25 million in microbicide research, which accounts for only 1% of its total investment in HIV/AIDS research.
Awa Coll-Seck, the director of policy, strategy, and research at UNAIDS, emphasized the importance of microbicide research, saying it is a method that "can allow women to protect themselves and their partners from infection without necessarily having to secure male cooperation."
A report by the International Working Group says that while condoms can provide an excellent level of protection if correctly and consistently used, many people — particularly women in socially vulnerable positions — find it difficult or impossible to persuade their partners to use them.
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