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 woridwide 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 #
5K24AI056933-09
Application #
8231476
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
2012-03-01
Budget End
2013-02-28
Support Year
9
Fiscal Year
2012
Total Cost
$144,347
Indirect Cost
$10,692
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; 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
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; 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
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
Kelesidis, Theodoros; Tran, Thuy Tien T; Brown, Todd T et al. (2016) 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 :
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
Stein, James H; Ribaudo, Heather J; Hodis, Howard N et al. (2015) A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness. AIDS 29:1775-83
Lake, Jordan E; McComsey, Grace A; Hulgan, Todd et al. (2015) Switch to Raltegravir From Protease Inhibitor or Nonnucleoside Reverse-Transcriptase Inhibitor Does not Reduce Visceral Fat In Human Immunodeficiency Virus-Infected Women With Central Adiposity. Open Forum Infect Dis 2:ofv059
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
Lake, Jordan E; Hoffman, Risa M; Tseng, Chi-Hong et al. (2015) Success of Standard Dose Vitamin D Supplementation in Treated Human Immunodeficiency Virus Infection. Open Forum Infect Dis 2:ofv068

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