My career goals are to 1) conduct high quality clinical studies to identify optimal strategies for managing antiretroviral therapy, with an emphasis on the use of antiretroviral therapy in women;2) to expand my research focus to include the study of mechanisms of atherosclerosis in HIV and;3) to develop novel methods for mentoring trainees in patient-oriented research. These goals will be achieved through the conduct of randomized clinical trials and through nested mechanistic studies.
The Specific Aims of my research program include:
Aim 1. To identify the optimal ART regimens for women of childbearing age both domestically and internationally.
Aim 2. To examine the effects of ART-related changes in immune function and inflammation on endothelial function and atherosclerosis progression in HIV infected adults starting ART.
Aim 3. To examine the impact of the substitution of the integrase inhibitor, raltegravir on lipohypertrophy in women with HIV infection who are currently receiving either a protease inhibitor or non-nucleoside based treatment regimen. The studies that provide the framework for my research and mentoring include 1) A randomized trial comparing the response to non-nucleoside reverse transcriptase inhibitor based treatment to protease inhibitor therapy among women who have and have not been previously exposed to nevirapine;2) A randomized trial comparing three compact regimens for initial therapy that does not include efavirenz;3) A sub-study nested into the trial described in 2) designed to measure changes in carotid intima medial thickness and brachial reactivity;4) A randomized trial evaluating the efficacy of raltegravir substitution for protease inhibitor or NNRTI based ART for the management of lipohypertrophy in women.

Public Health Relevance

HIV treatment is life-long and worldwide half of the people living with HIV are women. The studies proposed in this application will help to identify optimal treatment regimens for HIV-infected women and men and to determine how treatments compare in their impact on development of heart disease. The program will provide an opportunity to train physician scientists to conduct high quality research to address important clinical questions for people living with HIV.

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 #
5K24AI056933-07
Application #
7778325
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Roe, Joanad'Arc C
Project Start
2003-08-01
Project End
2014-02-28
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
7
Fiscal Year
2010
Total Cost
$144,347
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Kelesidis, Theodoros; Tran, Thuy Tien T; Brown, Todd T et al. (2017) Changes in plasma levels of oxidized lipoproteins and lipoprotein subfractions with atazanavir-, raltegravir-, darunavir-based initial antiviral therapy and associations with common carotid artery intima-media thickness: ACTG 5260s. Antivir Ther 22:113-126
Bhagwat, Priya; Ofotokun, Ighovwerha; McComsey, Grace A et al. (2017) Changes in abdominal fat following antiretroviral therapy initiation in HIV-infected individuals correlate with waist circumference and self-reported changes. Antivir Ther 22:577-586
Erlandson, Kristine M; Fiorillo, Suzanne; Masawi, Fadzai et al. (2017) Antiretroviral initiation is associated with increased skeletal muscle area and fat content. AIDS 31:1831-1838
Kelesidis, Theodoros; Jackson, Nicholas; McComsey, Grace A et al. (2016) Oxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection. AIDS 30:2625-2633
McComsey, Grace A; Moser, Carlee; Currier, Judith et al. (2016) Body Composition Changes After Initiation of Raltegravir or Protease Inhibitors: ACTG A5260s. Clin Infect Dis 62:853-62
Kelesidis, Theodoros; Moser, Carlee; Stein, James H et al. (2016) Changes in Markers of T-Cell Senescence and Exhaustion With Atazanavir-, Raltegravir-, and Darunavir-Based Initial Antiviral Therapy: ACTG 5260s. J Infect Dis 214:748-52
Hoffman, Risa M; Lake, Jordan E; Wilhalme, Holly M et al. (2016) Vitamin D Levels and Markers of Inflammation and Metabolism in HIV-Infected Individuals on Suppressive Antiretroviral Therapy. AIDS Res Hum Retroviruses 32:247-54
Dirajlal-Fargo, Sahera; Moser, Carlee; Brown, Todd T et al. (2016) Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s. Open Forum Infect Dis 3:ofw174
Hoffman, Risa M; Jaycocks, Amber; Vardavas, Raffaele et al. (2015) Benefits of PrEP as an Adjunctive Method of HIV Prevention During Attempted Conception Between HIV-uninfected Women and HIV-infected Male Partners. J Infect Dis 212:1534-43
Thio, Chloe L; Smeaton, Laura; Hollabaugh, Kimberly et al. (2015) Comparison of HBV-active HAART regimens in an HIV-HBV multinational cohort: outcomes through 144 weeks. AIDS 29:1173-82

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