Probiotics: The Potential for a Live Microbicide to Prevent HIV

Abstract

After early microbicide candidates failed in clinical trials to prevent HIV, recent news from the South African CAPRISA-004 study suggest that the new generation of vaginal microbicide gels using antiretroviral drugs like tenofovir could be effective and reduce HIV and herpes simplex virus (HSV)-2 acquisition.1 This landmark study greatly energized the field and revived enthusiasm for the development of female-controlled products to prevent HIV acquisition in women, and if ongoing trials confirm the CAPRISA-004 results lead to a licensed product by 2014. 2,3 While the field is getting closer to identifying an effective compound against vaginal HIV transmission, significant challenges remain, such as a sustained coitally-independent release of an effective drug, and a product formulation and administration that suits life circumstances of women in developing countries. Stigma continues to limit women’s access to HIV prevention strategies, and many women underestimate their own risk of HIV infection4. Thus, a microbicide product perceived to improve overall vaginal health may decrease possible acceptability barriers that a single purpose product associated with HIV prevention may face. In late May, the bi-annual global conference Microbicides 2010 held in Pittsburgh (USA) was attended by 1000 scientists and advocates, including more than 300 from Africa. The UCSF Bixby Center for Global Reproductive Health and the Consortium to Advance Multipurpose Innovations (CAMI) organized a Satellite Symposium titled ‘Probiotics: the Potential for a Live Microbicide’. The event provided a platform for researchers working in related fields to educate the conference audience and to initiate a discussion with other scientists, donors, advocates, members of federal agencies and world bodies, and regulatory experts in order to accelerate the development of probiotics for HIV prevention. A handful of small biotechnology companies and academic groups are working to develop a new generation of genetically enhanced probiotics by inserting genes which code for potent antiviral compounds into bacteria that naturally colonize the vagina. Once administered to the vagina, these next generation probiotics have the potential to serve as a sustained, self-replicating delivery system for antimicrobial compounds to combat reproductive tract infections, including HIV. The potential advantages of a probiotic microbicide continuously producing anti- HIV protein compounds in situ over conventional microbicide delivery systems such as gels and films include: i) periodic, possibly weekly or monthly replenishment vs. coitally dependent or daily dosing; ii) minimal disposal concerns, e.g. applicators; and iii) low-risk of developing HIV resistance in comparison to antiretroviral therapy commonly used in treatment, such as tenofovir. However, the field to date has been hampered by a relative lack of interest among donors due to competing HIV prevention technologies under development, lack of clarity regarding the regulatory pathway for licensure and general sensitivity surrounding genetically modified organisms (GMO), and financial fall-out from the recent worldwide recession.