Abstract

This study is designed to meet the goals of the RFA-DA-15-018: Developing Technologies and Tools to Monitor HIV Brain Reservoirs and How They May be Altered by Exposure to Substances of Abuse. To meet this challenge in the R21 phase, we propose to develop and validate a combined next generation sequencing (Pacific Biosciences single-molecule, real time (SMRT) sequencing) and bioinformatics platform to accurately measure and characterize HIV DNA populations in brain and lymph node tissues. In particular, this platform will be able to measure and identify proviral populations that are (i) intact and replication competent, (ii) intact but replication incompetent, and (iii) not intact. We will develop and validate the proposed platform based on international standard procedures for diagnostic molecular methods (i.e. CAP and OIE) using brain and lymph node tissues from HIV-infected individuals on optimized antiretroviral therapy for at least 2 years before death. Once developed and validated, we will use this technology in the R33 phase to determine how HIV DNA populates the brains of stimulant users and non-users.

Public Health Relevance

This project will develop and validate a next generation sequencing and bioinformatics platform that can quantify and sequence full-length HIV provirus in brain tissue to determine if the sampled HIV DNA populations are: (i) intact and replication competent, (ii) intact but replication incompetent, and (iii) not intact. Once optimized, we will determine how stimulant use is associated with how HIV DNA variants populate brain and lymph node tissues. 1

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DA041007-01
Application #
9052364
Study Section
Special Emphasis Panel (ZDA1-SXM-M (11))
Program Officer
Purohit, Vishnudutt
Project Start
2015-09-15
Project End
2018-07-31
Budget Start
2015-09-15
Budget End
2016-07-31
Support Year
1
Fiscal Year
2015
Total Cost
$387,500
Indirect Cost
$137,500

  Institution

Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Dubé, Karine; Gianella, Sara; Concha-Garcia, Susan et al. (2018) Ethical considerations for HIV cure-related research at the end of life. BMC Med Ethics 19:83
Eren, Kemal; Murrell, Ben (2018) RIFRAF: a frame-resolving consensus algorithm. Bioinformatics 34:3817-3824
Chaillon, Antoine; Essat, Asma; Frange, Pierre et al. (2017) Spatiotemporal dynamics of HIV-1 transmission in France (1999-2014) and impact of targeted prevention strategies. Retrovirology 14:15
Karris, Maile Y; Umlauf, Anya; Vaida, Florin et al. (2016) A randomized controlled clinical trial on the impact of CCR5 blockade with maraviroc in early infection on T-cell dynamics. Medicine (Baltimore) 95:e5315