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.
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.
|Shaffer, Douglas; Hughes, Michael D; Sawe, Fredrick et al. (2014) Cardiovascular disease risk factors in HIV-infected women after initiation of lopinavir/ritonavir- and nevirapine-based antiretroviral therapy in Sub-Saharan Africa: A5208 (OCTANE). J Acquir Immune Defic Syndr 66:155-63|
|Lake, J E; McComsey, G A; Hulgan, T et al. (2014) Switch to raltegravir decreases soluble CD14 in virologically suppressed overweight women: the Women, Integrase and Fat Accumulation Trial. HIV Med 15:431-41|
|Mwafongo, Albert; Nkanaunena, Kondwani; Zheng, Yu et al. (2014) Renal events among women treated with tenofovir/emtricitabine in combination with either lopinavir/ritonavir or nevirapine. AIDS 28:1135-42|
|Hulgan, Todd; Boger, M Sean; Liao, Diana H et al. (2014) Urinary eicosanoid metabolites in HIV-infected women with central obesity switching to raltegravir: an analysis from the women, integrase, and fat accumulation trial. Mediators Inflamm 2014:803095|
|Thio, Chloe L; Smeaton, Laura; Saulynas, Melissa et al. (2013) Characterization of HIV-HBV coinfection in a multinational HIV-infected cohort. AIDS 27:191-201|
|Brown, Todd T; Chen, Yun; Currier, Judith S et al. (2013) Body composition, soluble markers of inflammation, and bone mineral density in antiretroviral therapy-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr 63:323-30|
|Lake, Jordan E; Tseng, Chi-Hong; Currier, Judith S (2013) A pilot study of telmisartan for visceral adiposity in HIV infection: the metabolic abnormalities, telmisartan, and HIV infection (MATH) trial. PLoS One 8:e58135|
|Kelesidis, Theodoros; Yang, Otto O; Kendall, Michelle A et al. (2013) Dysfunctional HDL and progression of atherosclerosis in HIV-1-infected and -uninfected adults. Lipids Health Dis 12:23|
|Roberts, Christian K; Katiraie, Michael; Croymans, Daniel M et al. (2013) Untrained young men have dysfunctional HDL compared with strength-trained men irrespective of body weight status. J Appl Physiol (1985) 115:1043-9|
|Stein, James H; Brown, Todd T; Ribaudo, Heather J et al. (2013) Ultrasonographic measures of cardiovascular disease risk in antiretroviral treatment-naive individuals with HIV infection. AIDS 27:929-37|
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