Dr David Wilson (Credit: National Centre in HIV Epidemioogy & Clinical Research)

According to the World Health Organization, there are 23 microbicide products in various stages of clinical development. Some of them provide a physical barrier that keeps HIV and other genital pathogens from reaching the target cells; others maintain an acidic vaginal pH and enhance natural vaginal defense mechanisms, and the rest of them interfere with viral processes. However, an effective microbicide is not currently available.

While several phase 3 clinical trials have been carried out to evaluate the efficacy of various microbicides targeted for release in five to ten years, a new mathematical model suggests that these trials may not accurately portray the risk of HIV drug resistance and may result in high-risk microbicides passing clinical testing.

David Wilson, of the University of New South Wales, and colleagues have developed mathematical models to simulate clinical trials and population-level transmission of HIV and determine whether microbicide treatment under development that could lead to drug resistance might pass clinical trials. They based their models for both clinical trials and heterosexual transmission of HIV on epidemiological, clinical and behavioral data.

The models were based on an ongoing 12-month, placebo-controlled phase 3 clinical trial on 10,000 participants, for an antiretroviral microbicide. Since it is not yet known if such microbicides are high-risk microbicides (in which there is a high probability that the vagina will absorb the drug) or low-risk microbicides (with a low probability of absorption), the models simulated both scenarios.

The study predicts potential outcomes and risks that could arise from clinical trials on microbicides, even if they seem to yield satisfactory results. If microbicides that contain antiretroviral drugs are used by HIV-positive women (possibly unaware of this status of theirs), the drug can potentially cause a modification of the regular virus to a drug resistant virus. This undesirable consequence limits therapeutic options.

This study also predicts a previously unforeseen outcome of vaginal microbicides use: a greater benefit to men than for women. Drug resistant strains are considered less likely to be sexually transmitted, therefore women will have higher levels of drug resistance while the overall rate of transmission of the virus to men will be reduced, and fewer men will be infected.

The drug resistance concern arises since women in the current clinical trial are being tested once a month for HIV infection and those found to be infected are dropped from the trial. Therefore, high-risk microbicides could pass phase 3trials, as their potential to cause resistance will be masked by the frequent testing.

Despite their findings, the researchers say that microbicides could be effective and greatly reduce HIV incidence, provided that drug resistance and the level of drug absorption are carefully monitored and measured during the trials. Dr Wilson also added that "If the products are made available to the general population in the future then regular monitoring of users should be carried out.”

Other HIV researches previously covered by TFOT include identification of a gene that may influence the production of antibodies against HIV, discovery of a natural human protein that keeps mutant HIV strains from spreading, and neutralization of HIV in HIV-infected patients using a long term treatment with a combination antiretroviral therapy (cART).

Information regarding this research is available in this webpage of the University of New South Wales.