Vaginal microbicides and the prevention of HIV transmission

Abstract

Worldwide, nearly half of all individuals living with HIV are now women, who acquire the virus largely by heterosexual exposure. With an HIV vaccine likely to be years away, topical microbicide formulations applied vaginally or rectally are being investigated as another strategy for HIV prevention. A review of preclinical and clinical research on the development of microbicides formulated to prevent vaginal HIV transmission yielded 118 studies: 73 preclinical and 45 clinical. Preclinical research included in-vitro assays and cervical explant models, as well as animal models. Clinical research included phase I and II/IIb safety studies, and phase III efficacy studies. Whereas most phase I and phase II clinical trials have found microbicide compounds to be safe and well tolerated, phase III trials completed to date have not demonstrated efficacy in preventing HIV transmission. Topical microbicides are grouped into five classes of agents, based on where they disrupt the pathway of sexual transmission of HIV. These classes include surfactants/membrane disruptors, vaginal milieu protectors, viral entry inhibitors, reverse transcriptase inhibitors, and a fifth group whose mechanism is unknown. The trajectory of microbicide development has been toward agents that block more specific virus-host cell interactions. Microbicide clinical trials face scientifically and ethically complex issues, such as the choice of placebo gel, the potential for viral resistance, and the inclusion of HIV-infected participants. Assessment of combination agents will most likely advance this field of research.

One Percent Tenofovir Applied Topically to Humanized BLT Mice and Used According to the CAPRISA 004 Experimental Design Demonstrates Partial Protection from Vaginal HIV Infection, Validating the BLT Model for Evaluation of New Microbicide Candidates

“…The availability of a safe, inexpensive, and effective microbicide would have the potential to help stop the spread of HIV (9,30). Animal models are critical to the development, testing, and implementation of novel and effective microbicides.…”

“…currently undergoing large-scale clinical trials for efficacy in HIV prevention (7,9). One of these trials, the Center for the AIDS Program of Research in South Africa (CAPRISA) 004, recently reported that 1% tenofovir gel can partially prevent vaginal HIV transmission (1).…”

Human Immunodeficiency Virus Type 1 Nucleocapsid Inhibitors Impede trans Infection in Cellular and Explant Models and Protect Nonhuman Primates from Infection

“…Development of an effective vaccine or microbicide offers the greatest hope for protection for this vulnerable group. Recent setbacks in both fields, however, suggest that mucosal protection may be harder to achieve than previously anticipated (8,14,20,33).…”

Microbicides for the Prevention of HPV, HIV-1, and HSV-2: Sexually Transmitted Viral Infections

“…Sodium lauryl sulfate (SLS) is an anionic surfactant and has recently been tested as novel microbicidal agent that demonstrated signiicant lethal activity against a broad spectrum of STD pathogens, including HIV-1 [102]. This agent behaves as a liquid at room temperature and converts into gel form at body temperature to protect the STI transmission [103,104]. Therefore it can be used as invisible condoms.…”