Topical Microbicides to Prevent the Transmission of HIV: Formulation and delivery challenges and opportunities.

Although progress has been made in providing antivirals to HIV infected individuals and promoting some forms of HIV/AIDS prevention, such as abstinence, condom use and circumcision, there are still an estimated 7,000 new infections daily world-wide. Greater than 60% of the new infections are in girls and women under the age of 25, with the major HIV/AIDS risk factor for these women and girls in many developing countries being married and in a stable relationship. Thus, there is an urgent need to develop prevention methods that are not only safe, efficacious and acceptable, but also allow at risk individuals to actively protect themselves from infection. Although an AIDS vaccine is the "holy grail" of AIDS prevention, topical microbicides in the absence of an effective vaccine could enable individuals to prevent HIV transmission and infection. A topical microbicide is defined as a safe, effective and acceptable agent delivered in a gel, tablet, film and or device (e.g. vaginal ring or diaphragm) which prevents the transmission of HIV at the genital (vaginal and/or penile) and/or gastrointestinal (rectal) mucosa. Critical to this definition is the requirement of safety, which has in preclinical and clinical experience been shown to involve very subtle toxicological effects that are not normally encountered with dermal products or engender concerns with vaginal and gastrointestinal medicatants. This presentation will briefly review the preclinical and clinical status of the topical microbicide field and the role formulation and drug discovery is playing in the development of topical microbicides. Current challenges and the solutions being employed by investigators in the topical microbicide field will be placed into the context of the need to provide safe, effective and acceptable microbicide candidates formulated singly and/or in combinations in gels, rings and films for short and long term use in the female/male genital and gastrointestinal tracts. Specific challenges and the solutions being developed by topical microbicide investigators will be discussed, such as: co-formulation of biochemically diverse inhibitors; integration of acceptability measures and rheological characteristics to guide development of more acceptable microbicide gels and rings; development of biomarkers for microbicide and formulation safety and efficacy; and novel approaches for delivery of microbicides.