Lessons from HIV Research for Prevention: How to Prevent Mucosal Transmission of HIV
by Robert W. Buckheit, Jr.
October 27, 2016
Members of ImQuest BioSciences research team traveled to the HIV Research for Prevention meetings in Chicago last week to hear updates on research on topical microbicides and preventative pharmaceutical agents. Many sessions at the conference focused on initial events that result in productive infection following exposure to HIV. Currently, significant progress is being made throughout the world to identify infected individuals and place them on antiretroviral treatments. Although these treatments don’t cure infection, they serve the purpose of reducing the level of virus produced to undetectable levels (with associated clinical benefits) and thus reduce the potential of these individuals to pass virus on to their sexual partners. In addition, high risk populations are being offered pre-exposure prophylactic (PreP) drugs that have been shown to successfully protect uninfected partners from becoming infected. It has become very clear that a major way of reducing transmission of HIV to uninfected sexual partners is by utilizing means to identify infected individuals and reduce their viral loads and increase the incidence of condom use.
So what happens in the body when virus is introduced at the mucous membrane in the vagina, rectum or oral cavity? The mucous membrane epithelial layers are designed to function as effective barriers to infection, much like the skin protects the body from many microbial infections. Within the mucous membrane linings are immune cells that recognize and kill infectious organisms as well as innate factors that also restrict the ability of these organisms to initiate infection. HIV is somehow able to bypass these protective mechanisms and enter the body. Current evidence suggests that HIV enters the body through abrasions in these barriers of epithelial cells which line the vagina and rectum, often due to lesions induced by associated sexually transmitted viral, bacterial and fungal diseases. In some cases, it is thought that HIV hijacks its way through the mucosa by attaching to macrophage or dendritic cells, which transit through the mucous layer and deliver HIV to the very cells it is looking for - activated immune cells present in the stromal layer of the tissues. Once in the activated T cells and/or macrophage the clock is ticking. The infected cells respond to infection by secreting soluble factors that recruit additional immune system cells and these cells become additional targets of infection. As the infection smolders in these local sites, the opportunity to prevent infection begins to slip away. HIV enters the bloodstream and is disseminated throughout the body, establishing a productive systemic infection, which the immune system cannot suppress, and a variety of pathogenic effects that eventually lead to destruction of the immune system.
Our scientific team at ImQuest along with scientists around the world are working to develop products which will prevent the initial barrier to infection from being breached. Others scientists are working on means to prevent low level infection from turning into a systemic infection. It is now apparent that prevention products must act within hours to a single day after the introduction of virus to affect the outcome of HIV infection. HIV does not efficiently infect people – we know that infected individuals harbor a diverse selection of HIV variants and that a significant bottleneck is present which allows only rare variants to be transmitted. Lowering the viral load in infected individuals through treatment, reducing the ability of a virus to infect via PrEP, or treatment as prevention, using drugs or neutralizing antibodies as well as the use of topically applied microbicide products may all result in slowing and reversing the increasing number of HIV infected individuals in the world.
ImQuest scientists have successfully worked on the development of algorithms to identify and prioritize new microbicidal products for clinical development since the early 1990s, and have successfully acquired over 40 million dollars in NIH funding for prevention product development. In addition to assisting our clients with their product development needs, we have also successfully developed a microbicide product on behalf of our client, Samjin Pharmaceuticals, and we currently hold two INDs for the clinical development of our product as a vaginal gel for women and a dual vaginal and rectal product for men who have sex with men and women that engage in both vaginal and anal intercourse. We are currently hard at work on rectal and vaginal suppositories that will simplify the delivery of approved drugs to the vagina and rectum. Though these products were developed with the needs of women in resource poor areas of the world to be protected from HIV transmission in mind, a successful microbicide will be globally applicable. In addition, ImQuest scientists have intense interest and capability to develop products to prevent the transmission of herpes simplex virus, human papillomavirus, bacterial and fungal vaginosis organisms, Chlamydia, as well as hepatitis B and C viruses. Recently, Zika virus has been added to the list of sexually transmitted viruses where ImQuest can assist with preclinical and clinical product development. Lastly, ImQuest scientists can support the development of the appropriate formulation of new products for delivery to mucosal sites with a variety of on demand and long term delivery formats, including gels, creams, films, suppositories, rings and implantable devices.
Why not give us a call today to discuss your product development ideas and put our two decades of prevention product development experience to use. Contact Us to learn more.Return to the Blog