This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator.
SPECIFIC AIMS : #1: To measure carotid IMT in years 4-5 of the FRAM study and compare results in HIV+ subjects to control subjects from the CARDIA and MESA cohorts with adjustment for HIV independent risk factors, such as age, sex, race and smoking. To address this aim, we will model IMT as a function of HIV status, age, gender, ethnicity, and smoking. An additional predictor will indicate which control group (CARDIA or MESA) the subject belongs to, and we will also examine separate comparisons of HIV+ to each control group, with the HIV+ group restricted to those in the same age range as the controls. #2: To determine the association of IMT with traditional risk factors (lipid metabolism, glucose tolerance, fat distribution, smoking, physical activity and blood pressure) and with pro-atherosclerotic inflammatory markers (C-reactive protein (CRP), PAI-1, fibrinogen, IL-6, and interferon alpha) measured in FRAM participants in samples from the Year 1-2 initial FRAM Study visit and at the Year 4-5 follow up visit. For variables measured in FRAM 1, we will define predictors as the average of the baseline and follow-up measurement and evaluate whether the average performs better than baseline or followup separately. We will model the associations for HIV+ and each control group separately, and also build a combined model in conjunction with analyses for Aim 3. We will determine whether the risk factor-IMT relationships differ significantly among the HIV+ and control groups, using multiplicative interactive terms to evaluate the presence of effect modification. #3: To determine the fraction of the increased atherosclerosis observed in HIV that can be attributed to traditional risk factors, novel CVD risk factors and HIV infection as a means for identifying targets for future intervention or further investigation. We will compare the estimated coefficients for HIV estimated in Aim 1 to the estimated HIV effect in models that also control for the traditional risk factors, for the novel risk factors, and for both. The estimated effect of HIV itself will be the coefficient from the model that controls for both types of possible mediating risk factors. We will fit models that also control for antiretroviral (ARV) therapy history (see Aim 4), in case there are ARV effects that are not explained by mediating risk factors. These analyses will attempt to distinguish the effects of HIV per se from effects of ARV, when both are simultaneously controlled for all known potential mediators. #4: To determine the association of IMT with usage of ARV agents alone (i.e. specific drugs, classes of drugs) and in combinations. We will perform analyses like those for Aims 1-3, but using only HIV+ subjects and the primary predictors will be ARV variables rather than HIV. Indicators for current use and past use, along with numeric predictors of duration of years used and years since using will be examined.
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