The goal of this project is to conduct high quality patient oriented research with HIV infected patients which focuses on answering clinical and pathogenesis based questions concerning antiretroviral therapy and evaluates new and emerging strategies to improve the clinical management of antiretroviral therapy. The central hypothesis of the project is that carefully planned and analyzed studies can not only answer questions about specific treatment combinations, but can also provide insight into the pathogenesis of treatment responses and define strategies to manage patients in the clinic. Mentoring young investigators (M.P.H. students, Infectious Disease fellows, and junior faculty) will be a central goal of this project. These goals will be accomplished by conceiving, designing, initiating, carrying out, and analyzing randomized controlled trials in collaboration with local (UCSD AVRC), statewide (California Collaborative Treatment Group [CCTG]), and national (AIDS Clinical Trials Group [ACTG]) clinical trials organizations. As the overall Principal Investigator of the CCTG, I will be able to continue the tradition of fostering the development of junior investigators through active participation in CCTG studies. The primary research theme is to understand the antiretroviral exposure-response relationship and its implications for the pathogenesis and management of HIV.
The specific aims are: 1) To examine the mechanistic pathways leading to therapeutic failure of TDF + ABC by evaluating nucleoside plasma and intracellular exposure-response relationships. The study will use a unique clinical trial design (cross-over, pharmacokinetic evaluation of short-term viral dynamics) to evaluate the interaction between TDF and ABC. 2) To define the role of antiretroviral exposure-response relationships in HIV therapeutics.
Aim 2 A: To evaluate the value of therapeutic drug monitoring (TDM) to improve the management and outcome of antiretroviral therapy.
Aim 2 B: To define the impact of genetic differences (defined by allelic variants of single nucleoside polymorphisms) on exposure and response to lopinavir, the antiretroviral agent.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24AI064086-05
Application #
7770844
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Zhang, Hao
Project Start
2006-03-15
Project End
2011-02-28
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
5
Fiscal Year
2010
Total Cost
$170,129
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
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