136 Pre-Exposure Prophylaxis Robert M Grant Gladstone Inst of Virology and Immunology, Univ of California, San Francisco, USA

Antimicrobial agents have been used for prevention of malaria, tuberculosis disease, and maternal-to-child HIV transmission. Post-exposure prophylaxis (PEP) with antiretroviral agents is used in some urban centers after exposure to HIV by needle-stick or unprotected sex.  PEP is not widely available world-wide, partly because the efficacy of PEP is not known, and has never been evaluated in randomized clinical trials. Cases of PEP failures have been reported. Further, PEP fails if it is not initiated, as when the risks of specific contacts are not recognized due to anxiety, denial, substance use, or lack of information, knowledge, or social power.  Pre-exposure prophylaxis (PrEP) involves regular dosing of antiviral agents among individuals with recurring exposures, in contrast to dosing that is triggered by specific contact episodes (PEP). Regular dosing allows for drug levels to be present at the time of exposure, and does not require that individuals recognize the risk of every contact. In non-human primates, tenofovir disoproxl fumarate (TDF) has been 50% to 100% effective when administered before or just after a single challenge with simian immunodeficiency virus.  More recent animal research using multiple viral challenges will be reviewed. Available clinical findings indicate that daily oral TDF-containing regimens have been well-tolerated in small series of uninfected persons. Clinical trials will seek to confirm safety, and to determine if PrEP adds substantial protective benefit to those who also receive counseling, condoms, and STD care.  Some research will focus on risk behavior, drug resistance, and whether prior exposure to PrEP attenuates the course of infection, which may occur if expanding antiviral immune responses are spared by inhibition of viral replication in the first days after viral antigen exposure. Inclusion of diverse study populations in PrEP research has brought into prominence the social challenges that underlie the current fight against HIV/AIDS, which increasingly utilizes advanced-technology antiretroviral agents in disempowered populations who are highly impacted by the epidemic. The role of antiviral agents for prevention is not known for any group at this time, but will become clearer over the next few years if appropriate research can be performed and public discussion is fostered.