Novel microbicides against HIV
HIV infection remains a major global health concern. Highly active anti-retroviral therapy has reduced new infections but there are still millions of HIV positive individuals worldwide. This poses an urgent need for novel interventions against HIV. Over the last decade, scientists have investigated the potential for topically applied inhibitors of HIV, known as microbicides. Recently, a vaginal gel containing an inhibitor of HIV reverse transcriptase conferred approximately 40 % protection against infection, underscoring the effectiveness of the approach. Inflammation at vaginal or rectal mucosa has been linked with a higher likelihood of HIV infection. The primary objective of the EU-funded CHAARM (Combined highly active anti-retroviral microbicides) project was to develop new microbicides against HIV including the combinatorial use of anti-retroviral drugs. Project activities included drug discovery and development, and a comprehensive microbicide testing platform. A series of formulation studies were performed for microbicide delivery to the vaginal and rectal mucosae. The consortium also investigated the vaginal microbiome given its role in the susceptibility to HIV infection. Researchers used vaginal and colorectal tissue explants as ex vivo models alongside non-human primate models to test the pharmacokinetic properties and efficacy of a variety of microbicides. The most efficient proved to be a combination of two anti-retroviral drugs that was tested for safety in a phase I clinical trial. Structural analyses of the CCR5 receptor interaction with inhibitors and of HIV integrase and reverse transcriptase provided the basis for development of more effective inhibitors. Overall, the results of the CHAARM study enhanced our understanding of basic biological processes governing HIV infection and led to the identification of novel putative targets for treatment. Synergistic microbicides not only work against divergent HIV-1 strains, but are also less likely to generate viral strains resistant to multiple inhibitors. Watch the project’s video here.
Keywords
Microbicide, HIV, anti-retroviral drugs, transmission, inhibitor, reverse transcriptase integrase
