Browsing by Author "Tracy, Russell"
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Item Association of Gut Intestinal Integrity and Inflammation with Insulin Resistance in Adults Living with HIV in Uganda(AIDS Patient Care and STDs, 2019) Reid, Michael J.A.; Ma, Yifei; Golovaty, Iya; Okello, Samson; Sentongo, Ruth; Feng, Maggie; Tsai, Alexander C.; Kakuhikire, Bernard; Tracy, Russell; Hunt, Peter W.; Siedner, Mark; Tien, Phyllis C.We conducted a cross-sectional study of 148 HIV+ on HIV antiretroviral therapy and 149 HIV- adults in Mbarara, Uganda, to estimate the association between HIV infection and homeostasis model assessment of insulin resistance (HOMA-IR) using multivariable regression analysis. In addition, we evaluated whether intestinal fatty acid-binding protein (I-FABP), monocyte activation markers soluble (s)CD14 and sCD163, and proinflammatory cytokine interleukin 6 (IL-6) mediated this association. HOMA-IR was greater among HIV+ than HIV- adults [median (interquartile range): 1.3 (0.7–2.5) vs. 0.9 (0.5–2.4); p = 0.008]. In models adjusted for sociodemographic variables, diet, hypertension, and smoking history, HIV infection was associated with 37% [95% confidence intervals (95% CIs): 5–77] greater HOMA-IR compared with HIV- participants. The magnitude of association was greater when I-FABP was included as a covariate although the additive effect was modest (40% CI: 8–82). By contrast adding sCD14 to the model was associated with greater HOMA-IR (59%; 95% CI: 21–109) among HIV+ participants compared with HIV- participants. Among HIV+ participants, greater CD4 nadir was non-significantly associated with greater HOMA-IR (22%; 95% CI: -2 to 52). Each 5-unit increase in body mass index (BMI; 49% greater HOMA-IR; 95% CI: 18–87) and female sex (71%; 95% CI: 17–150) remained associated in adjusted models. In this study of mainly normal-weight Ugandan adults, HIV infection, female sex, and greater BMI were all associated with greater insulin resistance (IR). This association was strengthened modestly after adjustment for sCD14, suggesting possible distinct immune pathways to IR that are independent of HIV or related to inflammatory changes occurring on HIV treatment.Item Blood pressure trajectories and the mediated effects of body mass index and HIV‐related inflammation in a mixed cohort of people with and without HIV in rural Uganda(The Journal of Clinical Hypertension, 2019) Okello, Samson; Kim, June‐Ho; Sentongo, Ruth N.; Tracy, Russell; Tsai, Alexander C.; Kakuhikire, Bernard; Siedner, Mark J.We sought to describe changes in blood pressure and estimate the effect of HIV on blood pressure (BP) over 4 years of observation in a cohort of 155 HIV‐infected adults (≥40 years) on antiretroviral therapy (ART) and 154 sex‐ and age‐quartilematched, population‐based, HIV‐uninfected controls for four years in rural Uganda, we compared changes in blood pressure (BP) by HIV serostatus and tested whether body mass index and inflammation (high‐sensitivity C‐reactive protein and interleukin‐ 6) and immune activation (sCD14 and sCD163) mediated the effects of HIV on BP using hierarchical multivariate and two‐stage parametric regression models. Overall HIV‐uninfected participants had higher mean BP than HIV‐infected counterparts (differences in trend P < 0.0001 for diastolic BP and P = 0.164 for systolic BP). After initial declines in BP in both groups between years 1 and 2, BP moderately increased in both groups through year 4, with greater change over time observed in the HIVuninfected group. Body mass index mediated 72% (95%CI 57, 97) of the association between HIV and systolic BP. We found a minimal mediating effect of sCD14 on the relationship between HIV and SBP (9%, 95% CI 5%, 21%), but found no association between other HIV‐related biomarkers. Over four years of observation, HIV‐infected people in rural Uganda have lower BP than HIV‐uninfected counterparts despite having higher levels of inflammation. BMI, rather than measures of HIV‐associated inflammation, explained a majority of the difference in BP observed.Item Treated HIV Infection and Progression of Carotid Atherosclerosis in Rural Uganda: A Prospective Observational Cohort Study(Journal of the American Heart Association, 2021) Siedner, Mark J.; Bibangambah, Prossy; Kim, June-Ho; Lankowski, Alexander; Chang, Jonathan L.; Yang, Isabelle T.; Kwon, Douglas S.; North, Crystal M.; Triant, Virginia A.; Longenecker, Christopher; Ghoshhajra, Brian; Peck, Robert N.; Sentongo, Ruth N.; Gilbert, Rebecca; Kakuhikire, Bernard; Boum II, Yap; Haberer, Jessica E.; Martin, Jeffrey N.; Tracy, Russell; Hunt, Peter W.; Bangsberg, David R.; Tsai, Alexander C.; Hemphill, Linda C.; Okello, SamsonAlthough ≈70% of the world’s population of people living with HIV reside in sub-Saharan Africa, there are minimal prospective data on the contributions of HIV infection to atherosclerosis in the region. METHODS AND RESULTS: We conducted a prospective observational cohort study of people living with HIV on antiretroviral therapy >40 years of age in rural Uganda, along with population-based comparators not infected with HIV. We collected data on cardiovascular disease risk factors and carotid ultrasound measurements annually. We fitted linear mixed effects models, adjusted for cardiovascular disease risk factors, to estimate the association between HIV serostatus and progression of carotid intima media thickness (cIMT). We enrolled 155 people living with HIV and 154 individuals not infected with HIV and collected cIMT images at 1045 visits during a median of 4 annual visits per participant (interquartile range 3–4, range 1–5). Age (median 50.9 years) and sex (49% female) were similar by HIV serostatus. At enrollment, there was no difference in mean cIMT by HIV serostatus (0.665 versus 0.680 mm, P=0.15). In multivariable models, increasing age, blood pressure, and non–high- density lipoprotein cholesterol were associated with greater cIMT (P<0.05), however change in cIMT per year was also no different by HIV serostatus (0.004 mm/year for HIV negative [95% CI, 0.001–0.007 mm], 0.006 mm/year for people living with HIV [95% CI, 0.003–0.008 mm], HIV×time interaction P=0.25). CONCLUSIONS: In rural Uganda, treated HIV infection was not associated with faster cIMT progression. These results do not support classification of treated HIV infection as a risk factor for subclinical atherosclerosis progression in rural sub-Saharan Africa.