With the advent of highly active anti-retroviral therapy (HAART), significant progress has been achieved in the control of viral replication and prolongation of AIDS-free survival in HIV infected individuals. However, current therapeutic modalities do not effectively target or eliminate latent viral reservoirs. As a result, virus often rebounds after cessation of therapy. Significant side effects and drug-resistance are common due to the necessity for long-term multidrug therapy. An ultimate goal for anti-HIV therapy should therefore be virological eradication, i.e., to cure HIV infection. To date, the feasibility of virologic eradication has only been demonstrated in one HIV-infected patient given an allogeneic hematopoietic cell transplant (HCT) from a CCR5delta32 homozygous donor. Although this is an important proof-of-concept study, the likelihood of using HLA-matched and CCR5delta32 homozygous donor as a general therapeutic approach is remote. The overall objective of this U19 application is to explore strategies to introduce specific modifications in host and proviral DNA to target and eliminate latent HIV reservoir. The goal of this Core is to provide comprehensive support for the proof-of-concept studies in non-human primate models. This goal will be achieved through the execution of the following Specific Aims: (1). To provide animal resources, animal husbandry, and biosafety containment facilities necessary for the study of primate lentivirus infection in a non-human primate model;(2) To provide technical and clinical support for the implementation of non-human primate study protocols in this U19 application;(3) To provide laboratory expertise and analytical support for the monitoring of SHIV infection in macaques;and (4) To provide scientific and administrative oversight for the conduct of non-human primate studies. This Core will interact with all Projects and Cores of this U19.

Public Health Relevance

Despite significant progress has been achieved against HIV/AIDS, a cure remains elusive. Significant side effects and drug-resistance are common due to long-term use of multidrug therapies. A key objective of this U19 application will be to explore strategies to eradicate HIV in infected individuals. The goal of this Core is to provide comprehensive support for the proof-of-concept studies for these strategies in non-human primate models.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI096111-04
Application #
8691709
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Sedlak, Ruth Hall; Liang, Shu; Niyonzima, Nixon et al. (2016) Digital detection of endonuclease mediated gene disruption in the HIV provirus. Sci Rep 6:20064
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Stone, Daniel; Niyonzima, Nixon; Jerome, Keith R (2016) Genome editing and the next generation of antiviral therapy. Hum Genet 135:1071-82

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