Rectal microbicides: a new focus for HIV prevention
- University of Pittsburgh School of Medicine, Magee Womens Research Institute, Pittsburgh, Pennsylvania, USA
- Dr I McGowan, University of Pittsburgh School of Medicine, Magee Women's Research Institute, 204 Craft Avenue, Pittsburgh, PA 15213, USA;
- Accepted 29 June 2008
Rectal microbicides are needed for individuals who engage in unprotected anal intercourse (UAI). It is apparent that UAI occurs at a significant level in both men who have sex with men (MSM)1–3 and heterosexual women.4–6 Unfortunately, the rectal compartment is highly vulnerable to HIV transmission. A single layer of columnar epithelium separates the lumen from the lamina propria. The lamina propria is populated with a broad range of target cells including macrophages, dendritic cells and highly activated CD4 T lymphocytes expressing the CCR5 and CXCR4 HIV-1 co-receptors.7 It is likely that the immunology of the rectal mucosa is at least partly responsible for the 10–20-fold increased risk of HIV transmission associated with anal8 9 compared with vaginal10 11 intercourse. The purpose of this article is to provide an overview of the challenges and complexities of rectal microbicide development.
The development of topical microbicides over the past decade has focused on the prevention of HIV transmission associated with vaginal intercourse. Approximately 16 products have been evaluated in phase 1/2 safety studies and seven microbicides have advanced to phase 2B/3 effectiveness studies.12 Despite promising results in animal challenge experiments, the field still lacks proof of concept that a vaginal microbicide might reduce HIV transmission in humans. One possible explanation for the disappointing results from previous studies is that the first generation products (either surfactants (eg, nonoxynol-9) or fusion/entry inhibitors (eg, carraguard)) lacked the potency required to prevent HIV transmission. In some cases products may have had the potential to induce low-grade mucosal inflammation that might actually facilitate HIV acquisition.13 14 However, the microbicide research community remains optimistic that vaginal microbicides may have the potential to reduce HIV transmission. This optimism is focused on the recent development of the antiretroviral class of …