15 Nov Semen Impairs Efficacy of HIV Microbicides
Medical Research: What is the background for this study?
Dr. Münch: Most anti-HIV microbicides have potent antiviral activity in vitro but were largely inactive in clinical trials. Here we set out to explore whether the HIV infection enhancing activity of amyloid fibrils in human semen interferes with the antiviral efficacy of microbicides and antiviral drugs.
Medical Research: What are the main findings?
Dr. Münch: We found that all microbicides that target viral components (such as polyanions and neutralizing antibodies as well reverse transcriptase, integrase and protease inhibitors) are less effective in the presence of semen. Thus, the antiviral activity of microbicides determined in standard in vitro infection assays greatly underestimates the concentration of drug that is required to block HIV infection in the presence of semen. The only drug that blocked semen- and medium-exposed virus infection with similar antiviral efficacy was Maraviroc, a drug that prevents HIV cell entry by binding to the cellular CCR5 coreceptor.
Medical Research: What should clinicians and patients take away from your report?
Dr. Münch: Clinicians and patients that are involved in clinical trials aiming at evaluating topical microbicides should be aware that the drug levels that are required to prevent HIV-1 infection in vivo may be several times higher than those determined in cell culture in the absence of semen.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Münch: The antiviral activity of all future microbicides should be determined under conditions allowing to measure the infectivity enhancing effects of semen. In addition, only those microbicides should enter clinical trials that are active in the presence of semen. Finally, antagonizing or destroying seminal amyloid might not only decrease viral infectivity but also increase the antiviral efficacy of drugs.