Microbicides and other topical strategies to prevent vaginal transmission of HIV

• Published in: Nature Reviews: Immunology 2006-05, Vol.6 (5), p.371-382
• Main Authors: Lederman, Michael M, Offord, Robin E, Hartley, Oliver
• Format: Article
• Language: English
• Subjects: Administration, Topical; Anti-HIV Agents - administration & dosage; Anti-Infective Agents, Local - administration & dosage; Anti-Infective Agents, Local - pharmacology; Biomedical and Life Sciences; Biomedicine; Clinical trials; Condoms; Disease transmission; Epidemics; Female; Health risks; HIV; HIV - drug effects; HIV Infections - prevention & control; HIV Infections - transmission; Human immunodeficiency virus; Humans; Immune system; Immunology; Infections; Infectious diseases; Outbreaks; Pharmaceutical industry; Prevention; Public health; review-article; Vaccines; Vagina; Vagina - drug effects; Vagina - virology
• ISSN: 1474-1733; 1474-1741; 1365-2567
• DOI: 10.1038/nri1848

Key Points There is an urgent need to prevent the spread of HIV infection, especially among women, who are increasingly vulnerable to infection. Although the intact vaginal mucosa has features such as thickness, low pH, and hydrogen peroxide in secretions that resist HIV infection, trauma, infection, ulceration and inflammation can render this surface more susceptible to HIV. Although numerous factors have been implicated in protecting persons from HIV infection, only factors that diminish access to the HIV co-receptor CC-chemokine receptor 5 (CCR5) have been clearly linked to protection. Nonetheless, among persons at highest risk for HIV infection but who remain uninfected, the factors protecting most people are unidentified. Microbicides are topical agents that can be applied to mucosal surfaces to prevent acquisition of HIV. However, because many of these agents in development are not microbicidal, the term topical prevention strategies is often used. The most promising topical prevention strategies include those that target HIV directly, blocking entry into target cells or post-entry events needed for HIV replication, and those strategies that target host elements used by HIV to enter and infect host cells. Early hopes that a single topical prevention strategy might protect against HIV and other sexually transmissible pathogens might not be realized. Unfortunately, the necessary properties are shared only by membrane-disrupting agents that are often toxic to human cells from which the viral membrane is derived. Animal and tissue explant studies have been used to explore the mechanisms of HIV transmission and to test the feasibility and safety of topical prevention strategies. More work must be done to understand better the relationships of these and other models to human infection and to explore the safety of the candidate agents. In non-human primates, blocking the HIV co-receptor CCR5 provides high-level protection against vaginal challenge with chimeric simian–human immunodeficiency virus (SHIV). Combination antiviral strategies have revolutionized HIV therapeutics and combinations of topically applied inhibitors of HIV–host-cell fusion have provided high level protection against vaginal challenge with SHIV in non-human primates. The development of a successful topical prevention strategy will require coordination among basic scientists, formulation scientists, social scientists, clinicians and especially the pharmaceutical industry whose expertise