Miriam Hospital among National Research Group Awarded $20 Million NIH Grant


• Funding to be used for creation of drug delivery system to prevent HIV infection in women

Miriam Hospital among National Research GroupThe Miriam Hospital is part of a research collaboration that has received a $20 million grant from the National Institutes of Health (NIH) to develop an intravaginal ring (IVR) that can deliver powerful antiretroviral (ARV) drugs to prevent the spread of sexually transmitted HIV in women. Led by the Oak Crest Institute of Science, the five-year research initiative is funded under the NIH U19 Program, which supports collaborative projects involving multiple institutions.

Kathleen Morrow, PhD, the lead researcher at The Centers for Behavioral and Preventive Medicine at The Miriam Hospital, received $1.2 in funding from the NIH grant to study perceptibility, acceptability and adherence issues related to using microbicidal intravaginal rings – measures that can be used in subsequent clinical trials.

"I am very excited to be part of this important project. The joint effort builds on The Miriam's earlier research focused on developing effective HIV prevention products designed with the user in mind," says Morrow. "I believe that optimizing users' experiences can facilitate development of highly effective microbicide delivery systems that could contribute significantly to the reduction of the global AIDS burden."

Prevention of HIV infection continues to be a critical global health priority – with The World Health Organization reporting there are some 35 million people living with HIV in the world today. Approximately 70 percent of all people living with HIV are from Sub-Saharan Africa.

Intravaginal rings, available commercially for contraception and hormone replacement therapy, have shown promise as a drug delivery system to prevent HIV infection, but most designs currently under investigation can't deliver multiple-drug combinations of the many available antiretroviral drugs developed to combat HIV infection. While combinations of three antiretroviral drugs are highly successful in treatment of HIV infection, their use in an intravaginal ring platform for the prevention of HIV infection has not been possible until now. Further, the best combination of drugs to prevent sexually transmitted HIV infection is not known. This program will, for the first time, allow rigorous testing of a large group of  antiretroviral drugs in a systematic fashion to determine the best combination of drugs for HIV prevention.

"This project is, in large part, enabled by our pod-intravaginal ring (pod-IVR) platform," says principal investigator Marc Baum, PhD, president and senior faculty at Oak Crest.  "We have shown that the platform can deliver five different drugs simultaneously and at independently controlled dosages, which is unlike any other device under development today. In addition, the modular design of our pod-IVRs allows us to accelerate the development of prototypes, a critical element to testing many combinations as part of this program. Our technology platform also has the crucial advantage of scalability in manufacturing as the majority of the fabrication steps are identical regardless of the drug substances in the combination. This scalability and potential for economical manufacture will be crucial for any product to be used in the developing world."

Sustained-release approaches to drug delivery for the prevention of HIV infection, such as the pod-IVR, are especially appealing for use in the developing world, in contrast to daily therapies, where adherence is often an issue. Such devices are less expensive on a per-patient, per-day basis, they are capable of both rapid and sustained drug delivery for at least a month, and they sustain their effectiveness without refrigeration, an important consideration for use in resource-limited settings.

Previously, Morrow's team at The Miriam worked to evaluate and understand product acceptability in candidate microbicides, leading to Morrow pioneering the field's approach to perceptibility science. That is – unique evaluation of the sensory perceptions users experience when drug delivery systems (like the pod-IVR or topical gels and films) are used. Morrow's work suggests that what users feel and experience during use of such products will be a critical factor that drives consistent use. To date, the team has developed numerous evaluation tools to better understand these sensory perceptions and their relationships to use.

Other research teams working collaboratively on the IVR to deliver ARV drugs to prevent the spread of sexually transmitted HIV in women are from the Centers for Disease Control (CDC), the University of Texas Medical Branch, Johns Hopkins Medical Institute, the University of Colorado, Boulder, Scripps Research Institute, University of California, Los Angeles, Vanderbilt University and Auritec Pharmaceuticals.