The objectives of the Inhibitor Acquisition, Evaluation and Formulation Core are: 1) To acquire and initially characterize combinations of inhibitors of HIV-1 attachment, fusion and entry (AFE inhibitors) prior to their further evaluation as microbicide candidates in the in vitro and macaque model experimental systems; 2) To facilitate the formulation of these AFE inhibitor combinations in a way that is suitable for their testing for efficacy and safety in the macaque vaginal transmission model, then for safety in healthy women. The Core Leader will be John P. Moore, Ph.D., with Robin Shattock, Ph.D. acting as co-Leader. This Research Support Core will be located at the Weill Medical College of Cornell University, New York, NY. Its principal function will be to act as a central resource to support the individual Research Projects. The Core will obtain, by collaboration or purchase, sufficient quantities of suitable AFE inhibitors for use in all four Research Projects, including GMP-grade material when appropriate. This will ensure that a common set of reagents is used throughout the IPCP-HTM group. The Core will determine the potency of these inhibitors against a range of HIV-1 isolates in vitro, using well-established assays based on primary human and rhesus macaque lymphocytes, macrophages and dendritic cells. This work will ensure that only bona fide, active reagents are used in each of the Research Projects. The Core will identify which combinations of inhibitors are most suitable for further evaluation in the in vitro model systems (Research Projects I and II) and, in particular, in the rhesus macaque model (Research Project III). The Core will arrange expertise in microbicide formulation, and will supply properly formulated inhibitors to Research Project III, to ensure appropriate testing of candidate microbicides in the macaque vaginal transmission model. GMP grade inhibitors and formulations will be supplied to Research Project IV for clinical testing, when appropriate. The Core will also assist with the design and interpretation of experiments involving inhibitor combinations, in vitro and in the macaque.
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