The role of Preclinical and Clinical Pharmacology is to maximize the likelihood of success of an identified candidate, or to quickly remove a likely unsuccessful candidate from progressing into further testing. The primary objective of the Pharmacology Core (Core B) is to provide the investigators of the Martin Deianey Collaboratory to Eradicate HlV-1 Infection with the pharmacologic expertise to study therapeutic strategies that reduce the latent viral pool and animal model systems, and to evaluate the pharmacologic basis of viral persistence in humans. The Pharmacology Core will coordinate access to chemical libraries, assist with lead candidate production scale-up, coordinate animal toxicology studies, analyze biological matrices for drug concentrations (both antiretroviral and induction/eradication compounds), provide pharmacokinetic/ pharmacodynamic (PK/PD) modeling for optimal dose and dose frequency selection, and perform trial simulation to optimize design and sampling strategies. This Core will participate in all aspects of drug development for identifying and progressing lead induction/eradication candidates. The Core leadership team (Drs. Kashuba and Tan) has over 20 years combined experience in preclinical and clinical pharmacology, analytical chemistry, and Core management, and are well-suited to support the projects in the Collaboratory. This results in a Core which combines academic and industry resources to synergize strengths.

Public Health Relevance

The majority of drugs in development will not make it to market. The role of Preclinical and Clinical Pharmacology is to maximize the likelihood that a drug will be successful, or to identify and quickly remove a drug that will likely not be successful in going to market. This Core will provide support for all aspects of animal and human pharmacologic testing for induction/eradication compounds to support the investigators in the 4 Objectives of this proposal.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-JBS-A)
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University of North Carolina Chapel Hill
Chapel Hill
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Honeycutt, Jenna B; Sheridan, Patricia A; Matsushima, Glenn K et al. (2015) Humanized mouse models for HIV-1 infection of the CNS. J Neurovirol 21:301-9
King, Helen L; Keller, Samuel B; Giancola, Michael A et al. (2014) Pre-exposure prophylaxis accessibility research and evaluation (PrEPARE Study). AIDS Behav 18:1722-5
Manson McManamy, Mary E; Hakre, Shweta; Verdin, Eric M et al. (2014) Therapy for latent HIV-1 infection: the role of histone deacetylase inhibitors. Antivir Chem Chemother 23:145-9
Duverger, Alexandra; Wolschendorf, Frank; Anderson, Joshua C et al. (2014) Kinase control of latent HIV-1 infection: PIM-1 kinase as a major contributor to HIV-1 reactivation. J Virol 88:364-76
Spivak, Adam M; Andrade, Adriana; Eisele, Evelyn et al. (2014) A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy. Clin Infect Dis 58:883-90
Denton, Paul W; Long, Julie M; Wietgrefe, Stephen W et al. (2014) Targeted cytotoxic therapy kills persisting HIV infected cells during ART. PLoS Pathog 10:e1003872
Abreu, Celina M; Price, Sarah L; Shirk, Erin N et al. (2014) Dual role of novel ingenol derivatives from Euphorbia tirucalli in HIV replication: inhibition of de novo infection and activation of viral LTR. PLoS One 9:e97257
Archin, Nancie M; Margolis, David M (2014) Emerging strategies to deplete the HIV reservoir. Curr Opin Infect Dis 27:29-35
Liu, Pingyang; Xiang, Yanhui; Fujinaga, Koh et al. (2014) Release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein (snRNP) activates hexamethylene bisacetamide-inducible protein (HEXIM1) transcription. J Biol Chem 289:9918-25
Persaud, Deborah; Patel, Kunjal; Karalius, Brad et al. (2014) Influence of age at virologic control on peripheral blood human immunodeficiency virus reservoir size and serostatus in perinatally infected adolescents. JAMA Pediatr 168:1138-46

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