Herpes simplex virus and HIV: genital infection synergy and novel approaches to dual prevention.

Sexual transmission of HIV-1, in the absence of co-factors, is poorly efficient. Data support that herpes simplex virus type-2 (HSV-2) may increase a woman's susceptibility to HIV-1. Potential mechanisms by which HSV-2 serves as an HIV-1 enhancing co-factor include (1) initiation of a clinical or subclinical mucosal inflammatory response, (2) alteration of innate mucosal immunity and (3) weakening or breaching the protective genital epithelia. No clinical trial has examined prevention of primary HSV-2 infection to eliminate the major morbidities of this recurrent disease and as a strategy to reduce HIV-1 transmission. Topical administration of potent antivirals can achieve local concentrations that are orders of magnitude higher than those obtained with oral administration. This paper reviews major advances in oral and topical pre-exposure prophylaxis of HIV-1 and HSV-2 and, based on these data, hypothesizes that simultaneous prevention of sexual acquisition of HSV-2 and HIV-1 via topical antiretroviral agents will have a synergistic impact on both epidemics.