Despite the clinical success of antiretroviral therapy (ART), more people contract human immunodeficiency virus (HIV) infection daily than initiate ART. Since its inception in 2011, the Martin Delaney Collaboratory program has made important advances towards a cure for HIV, a much-needed effort to comprehensively combat the AIDS pandemic. The 2016 scientific agenda of the Collaboratory of AIDS Researchers for Eradication (CARE) seeks to more rapidly advance approaches for latency disruption and clearance into clinical testing. We hypothesize that the latent state of HIV can be reversed such that antigenic viral proteins are expressed, and that this intervention must be strategically combined with immunotherapies to allow the clearance of cells emerging from latency. Effective implementation of this strategy is expected to lead to the eradication of persistent HIV infection, a cure for AIDS. Our group now possesses substantial expertise previously not brought to bear on this problem, including the skills and tools of an expanded group of pharmaceutical partners. Our initial efforts will focus on the key objectives to facilitate clinical trials of eradication therapy: Detection of HIV antigen-positive cells (IRF I), Clearance of HIV antigen-positive cells (IRF II), Revealing and Clearing Unseen HIV (IRF 3). We envision an iterative process with insights gained in ex vivo, pre-clinical and clinical experiments carried forward to enhance the next step in clinical development and, importantly, fed back to scientists to refine their work, validate assays or hypotheses, and explore new directions. We are dedicated to working together in a nimble program, able to alter the course of our research as directed by our discoveries, convinced that together we will catalyze advances that will ultimately lead to the eradication of HIV infection.

Public Health Relevance

Despite the success of antiretroviral therapy (ART) in decreasing mortality for HIV-1-infected patients, ART has not cured the disease. A persistent viral reservoir in the T cells of HIV patients receiving potent ART is a significant barrier preventing an HIV cure. Including scientists from leading universities and Merck Research Laboratories, Qura Therapeutics, and Macrogenics, the Collaboratory of AIDS Researchers for Eradication (CARE) will seek to eradicate HIV infection by developing and testing therapies that will permanently destroy the viral reservoir.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
1UM1AI126619-01
Application #
9190915
Study Section
Special Emphasis Panel (ZAI1-VV-A (M1))
Program Officer
Lawrence, Diane M
Project Start
2016-07-14
Project End
2021-06-30
Budget Start
2016-07-14
Budget End
2017-06-30
Support Year
1
Fiscal Year
2016
Total Cost
$4,246,046
Indirect Cost
$791,786
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Lada, Steven M; Huang, Karissa; VanBelzen, D Jake et al. (2018) Quantitation of Integrated HIV Provirus by Pulsed-Field Gel Electrophoresis and Droplet Digital PCR. J Clin Microbiol 56:
Bradley, Todd; Ferrari, Guido; Haynes, Barton F et al. (2018) Single-Cell Analysis of Quiescent HIV Infection Reveals Host Transcriptional Profiles that Regulate Proviral Latency. Cell Rep 25:107-117.e3
Garrido, Carolina; Abad-Fernandez, Maria; Tuyishime, Marina et al. (2018) Interleukin-15-Stimulated Natural Killer Cells Clear HIV-1-Infected Cells following Latency Reversal Ex Vivo. J Virol 92:
Walters, Lucy C; Harlos, Karl; Brackenridge, Simon et al. (2018) Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding. Nat Commun 9:3137
Ruggiero, Alessandra; Cozzi-Lepri, Alessandro; Beloukas, Apostolos et al. (2018) Factors Associated With Persistence of Plasma HIV-1 RNA During Long-term Continuously Suppressive Firstline Antiretroviral Therapy. Open Forum Infect Dis 5:ofy032
Massanella, Marta; Yek, Christina; Lada, Steven M et al. (2018) Improved assays to measure and characterize the inducible HIV reservoir. EBioMedicine 36:113-121
Abdel-Mohsen, Mohamed; Kuri-Cervantes, Leticia; Grau-Exposito, Judith et al. (2018) CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells. Sci Transl Med 10:
Ke, Ruian; Conway, Jessica M; Margolis, David M et al. (2018) Determinants of the efficacy of HIV latency-reversing agents and implications for drug and treatment design. JCI Insight 3:
Salantes, D Brenda; Zheng, Yu; Mampe, Felicity et al. (2018) HIV-1 latent reservoir size and diversity are stable following brief treatment interruption. J Clin Invest 128:3102-3115
Clutton, Genevieve Tyndale; Jones, R Brad (2018) Diverse Impacts of HIV Latency-Reversing Agents on CD8+ T-Cell Function: Implications for HIV Cure. Front Immunol 9:1452

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