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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI096113-03
Application #
8497445
Study Section
Special Emphasis Panel (ZAI1-JBS-A)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$204,598
Indirect Cost
$23,254
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
White, Cory H; Beliakova-Bethell, Nadejda; Lada, Steven M et al. (2018) Transcriptional Modulation of Human Endogenous Retroviruses in Primary CD4+ T Cells Following Vorinostat Treatment. Front Immunol 9:603
Chaillon, Antoine; Gianella, Sara; Lada, Steven M et al. (2018) Size, Composition, and Evolution of HIV DNA Populations during Early Antiretroviral Therapy and Intensification with Maraviroc. J Virol 92:
Jiang, Guochun; Nguyen, Don; Archin, Nancie M et al. (2018) HIV latency is reversed by ACSS2-driven histone crotonylation. J Clin Invest 128:1190-1198
Dubé, Karine; Dee, Lynda; Evans, David et al. (2018) Perceptions of Equipoise, Risk-Benefit Ratios, and ""Otherwise Healthy Volunteers"" in the Context of Early-Phase HIV Cure Research in the United States: A Qualitative Inquiry. J Empir Res Hum Res Ethics 13:3-17
Prakash, Katya; Gianella, Sara; Dubé, Karine et al. (2018) Willingness to participate in HIV research at the end of life (EOL). PLoS One 13:e0199670
Papasavvas, Emmanouil; Lada, Steven M; Joseph, Jocelin et al. (2018) Analytical ART interruption does not irreversibly change pre-interruption levels of cellular HIV. AIDS :
Honeycutt, Jenna B; Liao, Baolin; Nixon, Christopher C et al. (2018) T cells establish and maintain CNS viral infection in HIV-infected humanized mice. J Clin Invest 128:2862-2876
Power, Jennifer; Westle, Andrew; Dowsett, Gary W et al. (2018) Perceptions of HIV cure research among people living with HIV in Australia. PLoS One 13:e0202647
Marsden, Matthew D; Wu, Xiaomeng; Navab, Sara M et al. (2018) Characterization of designed, synthetically accessible bryostatin analog HIV latency reversing agents. Virology 520:83-93
Beliakova-Bethell, Nadejda; Hezareh, Marjan; Wong, Joseph K et al. (2017) Relative efficacy of T cell stimuli as inducers of productive HIV-1 replication in latently infected CD4 lymphocytes from patients on suppressive cART. Virology 508:127-133

Showing the most recent 10 out of 221 publications