Candidate: Dr. Thor Wagner is a senior fellow in Pediatric Infectious Diseases at the University of Washington. His long-term goal is a career in pediatric patient-orientated HIV research. Environment: Dr. Wagner has proposed mentorship from an established pediatric HIV researcher, collaboration and consultation with various local experts, as well as a comprehensive didactic curriculum, that takes advantage of the rich academic HIV research community in Seattle, WA. Research: The hypothesis, HIV-1 replication persists at low levels in macrophages during effective antiretroviral therapy, will be addressed by three aims: (1) evaluate HIV-1 in induced sputa, which is rich in macrophages, for genetic evidence of viral replication over time;(2) determine the relative rate of viral replication in sputa macrophages compared to lymphocytes;(3) explore the relative activity of different antiretroviral regimens, including those with and without drugs that appear to be more active in macrophages, on measures of viral replication in sputum samples.
In Aim 1, multiple single-genome HIV-1 sequences (SGS) derived from annual induced sputum specimens and peripheral blood mononuclear cells collected over five years from 15 children will be analyzed for evidence of replication.
In Aim 2, sorting of sputa cells by flow cytometry followed by SGS will precisely define the cell types with evidence of viral replication.
In Aim 3, HIV-1 replication will be gauged in sputum specimens from adults who are or are not treated with tenofovir and non-nucleoside reverse transcriptase inhibitors, which appear to be more active in macrophages. Relevance: Millions of HIV-1 infected individuals face a lifelong challenge of averting antiretroviral resistance. Persistent low-level viral replication despite antiretroviral therapy substantially increases the risk of antiretroviral resistance. Our studies will provide insight into persistent HIV-1 replication during antiretroviral therapy and whether specific drugs are more effective in suppressing viral replication in macrophages.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI077357-04
Application #
8110480
Study Section
Special Emphasis Panel (ZAI1-ESB-A (S3))
Program Officer
Livnat, Daniella
Project Start
2008-09-01
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
4
Fiscal Year
2011
Total Cost
$129,465
Indirect Cost
Name
Seattle Children's Hospital
Department
Type
DUNS #
048682157
City
Seattle
State
WA
Country
United States
Zip Code
98105