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Protecting people against HIV infection is an urgent global health priority, particularly in the developing world. Dr Marc Baum of the Oak Crest Institute of Science in the US writes about his research into developing intravaginal ring technologies which can release drugs to protect women from HIV


Fabrication of intravaginal rings on a laboratory-scale injection molding system (left). View of a pod in the Oak Crest intravaginal ring releasing drug through a delivery channel into vaginal fluid (center). Close up of the 4 pod intravaginal ring (right).


Protecting women from HIV


The battle against HIV is being fought on many fronts, with researchers looking at the structure of the virus, developing strategies to prevent it from spreading, and treating systemic infection with new methods. Based at the Oak Crest Institute of Science in California, Dr. Marc Baum is part of a research team investigating new methods of delivering drugs to prevent the virus from spreading after the initial infection event. “The fundamental goal of our research is to develop intravaginal ring (IVR) technologies that are proven to be safe and effective in protecting women from contracting HIV,” he outlines. There are different strategies to achieve this goal, one of which is to use multi-purpose technologies that combine more than one preventative technology in a single device. “With vaginal rings, that could be a device showing promise for protection from HIV infection, but also having a contraceptive component. Or, you could have an IVR that’s protective against two sexually transmitted infections at the same time. So you have an HIV ring that is also protective against genital herpes (HSV),” continues Dr Baum. “Those are parallel approaches to achieve a ring that is protective against HIV infection. That’s really fundamental, the most important of our goals.”


Effective microbicides There is no clear pathway to follow in this work. Understanding how the virus works is fundamentally important to developing an effective microbicide, but earlier approaches were not successful in clinical trials, largely because of safety problems. “The viral lifecycle is quite well-known. A logical approach is targeting different aspects of the viral lifecycle with a prophylaxis, so that you minimise the


and begins to replicate once it enters target immune cells. Once it reaches a certain threshold, these infections can then spread through the lymphatic system and become systemic. That’s when you have a problem – at that point it’s too late. But if you can interrupt the proliferation of this starting population in the vaginal tissues at this very early stage, you can potentially prevent systemic infection,” he explains. This is not only about preventing


Once the virus reaches a certain threshold, these infections


can spread through the lymphatic system and become systemic. That’s when you have a problem. But if you


population in the vaginal tissues, at this very early stage, you can potentially prevent systemic infection


can interrupt the proliferation of this starting


chances of the virus going beyond the initial stages and infecting the host systemically,” says Dr. Baum. It may seem counter-intuitive to consider prophylaxis when the host is already infected, but Dr. Baum says the part of the virus that establishes itself in the early stages of infection is very localised. “It appears that, when somebody is infected by the virus, it traverses the mucus in the vaginal epithelium, passes into the vaginal tissues,


the spread of the virus, but eradicating it in the host, so researchers at Oak Crest are developing a novel IVR platform to simultaneously release multiple drugs that target the virus at different stages of infection. This work builds on an understanding of how the virus establishes itself in the host and its subsequent development. “The initial step is attachment and then incorporation into the cell. An entry inhibitor can potentially


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