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

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
4R33DA041007-04
Application #
9667538
Study Section
Special Emphasis Panel (ZDA1)
Program Officer
Berton, Olivier Roland
Project Start
2015-09-15
Project End
2020-07-31
Budget Start
2018-08-01
Budget End
2019-07-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
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
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