Treated HIV Infection and Progression of Carotid Atherosclerosis in Rural Uganda: A Prospective Observational Cohort Study.
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ABSTRACT:
SUBMITTER: Siedner MJ
PROVIDER: S-EPMC8477876 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSoluble Tumor Necrosis Factor Weak Inducer of Apoptosis (sTWEAK) has been proposed as a novel biomarker of cardiovascular disease risk. This study compares levels of sTWEAK, sCD163 and the sCD163/sTWEAK ratio in HIV-infected and uninfected patients and their associations with cardiovascular and inflammatory factors.MethodsThe data for our analysis come from 274 HIV-infected adults and 59 controls. HIV participants were on stable antiretroviral therapy (ART). Wilcoxon-Mann-Whitney tests were used for comparing markers between HIV-infected participants with HIV viral load <50 copies/mL (aviremic group), HIV-infected participants with detectable viremia (HIV-1 RNA ≥50 copies/mL; viremic group) and HIV negative participants. Multivariable quantile regression analyses were used to assess associations of sTWEAK and sCD163 with other markers of inflammation and carotid intima-media thickness (cIMT).ResultsOverall, 74% of participants were male; 59% were African-Americans; median age was 40 years and CD4 595 cells/mm3. Overall, HIV-infected participants had reduced sTWEAK and increased sCD163 levels compared to HIV-uninfected participants (p = 0.0001 for both markers). In addition, these biomarkers were significantly different between HIV-infected viremic and aviremic patients (p ≤ 0.01 for both markers). In multivariable models, sTWEAK and sCD163 in aviremic patients were significantly correlated with common carotid artery IMT (p ≤ 0.05). In HIV-infected aviremic participants, sTWEAK and sCD163 were both associated with IL-6, CD14 + CD16 + monocytes (p ≤ 0.02); additionally, sCD163 was associated with D-dimer- (β = -69.5, 0.05), VCAM (β = 72.4, p = 0.05), TNF RI (β = 91.1, p < 0.01), and TNF RII (β = 87.8, p < 0.01).ConclusionsHIV-infected participants showed increased systemic inflammatory and monocyte activation markers. Soluble CD163 and sTWEAK levels were associated with carotid intima-media thickness.
| S-EPMC8559006 | biostudies-literature
Project description:BackgroundIndividuals infected with human immunodeficiency virus (HIV) live longer as a result of effective treatment, but long-term consequences of infection, treatment, and immunological dysfunction are poorly understood.MethodsWe prospectively examined 1011 women (74% HIV-infected) in the Women's Interagency HIV Study and 811 men (65% HIV-infected) in the Multicenter AIDS Cohort Study who underwent repeated B-mode carotid artery ultrasound imaging in 2004-2013. Outcomes included changes in right common carotid artery intima-media thickness (CCA-IMT) and new focal carotid artery plaque formation (IMT >1.5 mm) over median 7 years. We assessed the association between HIV serostatus and progression of subclinical atherosclerosis, adjusting for demographic, behavioral, and cardiometabolic risk factors.ResultsUnadjusted mean CCA-IMT increased (725 to 752 µm in women, 757 to 790 µm in men), but CCA-IMT progression did not differ by HIV serostatus, either in combined or sex-specific analyses. Focal plaque prevalence increased from 8% to 15% in women and 25% to 34% in men over 7 years. HIV-infected individuals had 1.6-fold greater risk of new plaque formation compared with HIV-uninfected individuals (relative risk [RR] 1.61, 95% CI, 1.12-2.32), adjusting for cardiometabolic factors; the association was similar by sex. Increased plaque occurred even among persistently virologically suppressed HIV-infected individuals compared with uninfected individuals (RR 1.56, 95% CI, 1.07-2.27). HIV-infected individuals with baseline CD4+ ? 500 cells/µL had plaque risk not statistically different from uninfected individuals.ConclusionsHIV infection is associated with greater increases in focal plaque among women and men, potentially mediated by factors associated with immunodeficiency or HIV replication at levels below current limits of detection.
| S-EPMC4607734 | biostudies-literature
Project description:BackgroundUp to 50 % of HIV-infected persons in sub-Saharan Africa are lost from care between HIV diagnosis and antiretroviral therapy (ART) initiation. Structural barriers, including cost of transportation to clinic and poor communication systems, are major contributors.MethodsWe conducted a prospective, pragmatic, before-and-after clinical trial to evaluate a combination mobile health and transportation reimbursement intervention to improve care at a publicly operated HIV clinic in Uganda. Patients undergoing CD4 count testing were enrolled, and clinicians selected a result threshold that would prompt early return for ART initiation or further care. Participants enrolled in the pre-intervention period (January - August 2012) served as a control group. Participants in the intervention period (September 2012 - November 2013) were randomized to receive daily short message service (SMS) messages for up to seven days in one of three formats: 1) messages reporting an abnormal result directly, 2) personal identification number-protected messages reporting an abnormal result, or 3) messages reading "ABCDEFG" to confidentially convey an abnormal result. Participants returning within seven days of their first message received transportation reimbursements (about $6USD). Our primary outcomes of interest were time to return to clinic and time to ART initiation.ResultsThere were 45 participants in the pre-intervention period and 138 participants in the intervention period (46, 49, and 43 in the direct, PIN, and coded groups, respectively) with low CD4 count results. Median time to clinic return was 33 days (IQR 11-49) in the pre-intervention period and 6 days (IQR 3-16) in the intervention period (P < 0.001); and median time to ART initiation was 47 days (IQR 11-75) versus 12 days (IQR 5-19), (P < 0.001). In multivariable models, participants in the intervention period had earlier return to clinic (AHR 2.32, 95 %CI 1.53 to 3.51) and earlier time to ART initiation (AHR 2.27, 95 %CI 1.38 to 3.72). All three randomized message formats improved time to return to clinic and time to ART initiation (P < 0.01 for all comparisons versus the pre-intervention period).ConclusionsA combination of an SMS laboratory result communication system and transportation reimbursements significantly decreased time to clinic return and time to ART initiation after abnormal CD4 test results.Trial registrationsClinicaltrials.gov NCT01579214 , approved 13 April 2012.
| S-EPMC4494725 | biostudies-literature
Project description:ObjectiveTo evaluate plasma acylcarnitine profiles and their relationships with progression of carotid artery atherosclerosis among individuals with and without HIV infection.DesignProspective cohort studies of 499 HIV-positive and 206 HIV-negative individuals from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study.MethodsTwenty-four acylcarnitine species were measured in plasma samples of participants at baseline. Carotid artery plaque was assessed using repeated B-mode carotid artery ultrasound imaging in 2004-2013. We examined the associations of individual and aggregate short-chain (C2-C7), medium-chain (C8-C14) and long-chain acylcarnitines (C16-C26) with incident carotid artery plaque over 7 years.ResultsAmong 24 acylcarnitine species, C8-carnitines and C20 : 4-carnitines showed significantly lower levels comparing HIV-positive to HIV-negative individuals (false discovery rate adjusted P < 0.05); and C20-carnitines and C26-carnitines showed significantly higher levels in HIV positive using antiretroviral therapy than those without antiretroviral therapy (false discovery rate adjusted P < 0.05). In the univariate analyses, higher aggregated short-chain and long-chain acylcarnitine scores were associated with increased risk of carotid artery plaque [risk ratios (RRs) = 1.22 (95% confidence interval 1.02-1.45) and 1.20 (1.02-1.41) per SD increment, respectively]. The association for the short-chain acylcarnitine score remained significant [RR = 1.23 (1.05-1.44)] after multivariate adjustment (including traditional cardiovascular disease risk factors). This association was more evident in HIV-positive individuals without persistent viral suppression [RR = 1.37 (1.11-1.69)] compared with those with persistent viral suppression during follow-up [RR = 1.03 (0.76-1.40)] or HIV-negative individuals [RR = 1.02 (0.69-1.52)].ConclusionIn two HIV cohorts, plasma levels of most acylcarnitines were not significantly different between HIV-positive and HIV-negative individuals. However, higher levels of aggregated short-chain acylcarnitines were associated with progression of carotid artery atherosclerosis.
| S-EPMC6457128 | biostudies-literature
Project description:Epidemiological studies have demonstrated associations between long-term exposure to traffic-related air pollution and coronary heart disease (CHD). Atherosclerosis is the principal pathological process responsible for CHD events, but effects of traffic-related air pollution on progression of atherosclerosis are not clear. This study aimed to investigate associations between long-term exposure to traffic-related air pollution and progression of carotid artery atherosclerosis.Healthy volunteers in metropolitan Vancouver, Canada.509 participants aged 30-65 years were recruited and followed for approximately 5 years. At baseline and end of follow-up, participants underwent carotid artery ultrasound examinations to assess atherosclerosis severity, including carotid intima-media thickness, plaque area, plaque number and total area. Annual change of each atherosclerosis marker during the follow-up period was calculated as the difference between these two measurements divided by years of follow-up. Living close to major roads was defined as ?150 m from a highway or ?50 m from a major road. Residential exposures to traffic-related air pollutants including black carbon, fine particles, nitrogen dioxide and nitric oxide were estimated using high-resolution land-use regression models. The data were analysed using general linear models adjusting for various covariates.At baseline, there were no significant differences in any atherosclerosis markers between participants living close to and those living away from major roads. After follow-up, the differences in annual changes of these markers between these two groups were small and not statistically significant. Also, no significant associations were observed with concentrations of traffic-related air pollutants including black carbon, fine particles, nitrogen dioxide and nitric oxide.This study did not find significant associations between traffic-related air pollution and progression of carotid artery atherosclerosis in a region with lower levels and smaller contrasts of ambient air pollution.
| S-EPMC3987708 | biostudies-literature
Project description:BackgroundHealthy lifestyles are effective means to reduce major cardiovascular events. However, little is known about the association of healthy lifestyles with development of carotid atherosclerosis at the early stage of cardiovascular diseases (CVDs).MethodsWe enrolled participants from Fujian province in the China PEACE MPP project. We calculated a healthy lifestyle score by adherence to non-smoking, sufficient physical activity, healthy diet and healthy body mass index. Cox proportional hazards regression models and restricted cubic splines (RCS) were used to explore the association between the healthy lifestyles and rapid progression of carotid plaque.Results8379 participants were included (mean age: 60.6 ± 8.3 years, 54.6 % female), with a median follow-up of 1.2 years (inter quartile range: 1.0-1.6). RCS showed a significant inverse association between the healthy lifestyle score and progression of carotid plaque. Participants with "intermediate" (HR: 0.72 [95 % confidence interval (CI): 0.65-0.80]) or "ideal" (HR: 0.68 [0.59-0.78]) adherence to healthy lifestyles had a lower risk of progression of carotid plaque compared to those with "poor" adherence. Age, sex, occupation, income, residence type and metabolic status were significant factors influencing the relationship. Farmers benefited more in non-smoking and sufficient physical activity compared to non-farmers, and participants with lower income or without dyslipidaemia benefited more in sufficient physical activity and healthy diet compared to their counterparts (p-for-interaction < 0.05).ConclusionsHealthy lifestyles were associated with lower risk of progression of carotid plaque in populations with atherosclerosis. Promotion of healthy lifestyles from the early stage of carotid atherosclerosis could reduce the burden of CVDs in China.
| S-EPMC10979119 | biostudies-literature
Project description:Although cerebrovascular diseases have been considered as risk factors for cognitive decline and dementia, the associations between atherosclerosis and Alzheimer's disease (AD) have not been fully examined and remain controversial. The aim of this three-year prospective study was to investigate whether arotid artery atherosclerosis accelerates cognitive impairment in AD patients. The association of carotid intimal medial thickness (IMT) with prospective trajectories of cognitive function was assessed among 521 patients with light to moderate AD, and 437 AD patients were followed up annually for 3 years. Participants underwent initial carotid ultrasonography and repeated neuropsychological testing every year. Mixed-effects regression analyses were adjusted to estimate the effect of carotid IMT and other adjusting variables. The results of the present study indicated that carotid IMT was significantly associated with various measures of cognitive function. Furthermore, AD patients with higher carotid IMT values had a faster decline in cognitive scores in a variety of neuropsychological tests, particularly in verbal and non-verbal memory, semantic fluency and executive function. The present prospective study showed that carotid atherosclerosis is a predictive factor regarding the progression of cognitive impairment in AD patients, suggesting that early detection and treatment of vascular risk factors may prevent or at least postpone the evolution of the disease.
| S-EPMC5525969 | biostudies-other
Project description:ImportanceLipid metabolism disruption and excess risk of cardiovascular disease (CVD) have been observed in HIV-infected individuals, but the associations among HIV infection, plasma lipidome, and CVD risk have not been well understood.ObjectiveTo evaluate plasma lipidomic profiles and their associations with carotid artery atherosclerosis in individuals with HIV and individuals without HIV.Design, setting, and participantsProspective analysis in the Women's Interagency HIV Study and Multicenter AIDS Cohort Study during a 7-year follow-up (from 2004-2006 to 2011-2013) at multicenter HIV cohorts in the United States. The study included 737 participants aged 35 to 55 years (520 with HIV and 217 without HIV) without CVD or carotid artery plaque at baseline. Data were analyzed between April 2017 and July 2019.ExposuresTwo hundred eleven plasma lipid species.Main outcomes and measuresPoisson regression was used to examine the associations of baseline lipid species with risk of plaque measured by repeated B-mode carotid artery ultrasonography imaging.ResultsOf the 737 included participants, 398 (54%) were women, 351 (48%) were African American (non-Hispanic), 156 of 737 (21%) were nonwhite Hispanic, and the mean (SD) age was 45 (6) years. After adjusting for demographic and behavioral factors, we identified 12 lipid species, representing independent signals for 10 lipid classes, associated with risk of plaque. Nine lipid species remained significant after further adjusting for conventional CVD risk factors, although many of them showed moderate to high association with conventional blood lipids (eg, total and low-density lipoprotein cholesterols and triglycerides). Cholesteryl ester (16:1) (risk ratio [RR] per standard deviation, 1.28; 95% CI, 1.08-1.52), ceramide (16:0) (RR, 1.29; 95% CI, 1.02-1.63), lysophosphatidylcholine (20:4) (RR, 1.28; 95% CI, 1.05-1.58), lysophosphatidylethanolamine (16:0) (RR, 1.28; 95% CI, 1.05-1.57), phosphatidylethanolamine (38:6) (RR, 1.33; 95% CI, 1.08-1.64), phosphatidylethanolamine-plasmalogen (36:2) (RR, 1.25; 95% CI, 1.04-1.52), phosphatidylserine-plasmalogen (36:3) (RR, 1.19; 95% CI, 1.00-1.43), and triacylglycerol (54:6) (RR, 1.26; 95% CI, 1.04-1.54) were associated with increased risk of plaque, while phosphatidylcholine (36:4) (RR, 0.65; 95% CI, 0.54-0.77) was associated with decreased risk of plaque. Most of these plaque-increased lipid species showed higher levels in individuals with HIV, particularly among individuals with HIV using antiretroviral therapy compared with individuals without HIV. Network analysis identified 9 lipid modules, and 2 modules composed of triacylglycerols and phosphatidylcholines with long and unsaturated acyl chains, respectively, showed the strongest associations with increased risk of plaque.Conclusions and relevanceThis study identified multiple plasma lipid species associated with carotid artery atherosclerosis, and alterations in these lipid species might be associated with HIV infection and antiretroviral therapy. Our data suggest unfavorable associations of long-chain and unsaturated triacylglycerols and phosphatidylcholines with carotid artery plaque formation.
| S-EPMC6813587 | biostudies-literature
Project description:Local HIV epidemiology data are critical in determining the suitability of a population for HIV vaccine efficacy trials. The objective of this study was to estimate the prevalence and incidence of, and determine risk factors for HIV transmission in a rural community-based HIV vaccine preparedness cohort in Masaka, Uganda.Between February and July 2004, we conducted a house-to-house HIV sero-prevalence survey among consenting individuals aged 18-60 years. Participants were interviewed, counseled and asked to provide blood for HIV testing. We then enrolled the HIV uninfected participants in a 2-year HIV sero-incidence study. Medical evaluations, HIV counseling and testing, and sample collection for laboratory analysis were done quarterly. Sexual risk behaviour data was collected every 6 months.The HIV point prevalence was 11.2%, and was higher among women than men (12.9% vs. 8.6%, P = 0.007). Risk factors associated with prevalent HIV infection for men were age <25 years (aOR = 0.05, 95% CI 0.01-0.35) and reported genital ulcer disease in the past year (aOR = 2.17, 95% CI 1.23-3.83). Among women, being unmarried (aOR = 2.59, 95% CI 1.75-3.83) and reported genital ulcer disease in the past year (aOR = 2.40, 95% CI 1.64-3.51) were associated with prevalent HIV infection. Twenty-one seroconversions were recorded over 2025.8 person-years, an annual HIV incidence of 1.04% (95% CI: 0.68-1.59). The only significant risk factor for incident HIV infection was being unmarried (aRR = 3.44, 95% CI 1.43-8.28). Cohort retention after 2 years was 87%.We found a high prevalence but low incidence of HIV in this cohort. HIV vaccine efficacy trials in this population may not be feasible due to the large sample sizes that would be required. HIV vaccine preparatory efforts in this setting should include identification of higher risk populations.
| S-EPMC3108994 | biostudies-other
Project description:To determine the effect of statins on the progression of subclinical atherosclerosis in a population of HIV-infected adults on antiretroviral therapy.Double-blind, randomized clinical trial.Stopping Atherosclerosis and Treating Unhealthy Bone with RosuvastatiN in HIV infection was a 96-week double-blind, randomized clinical trial of 10?mg daily rosuvastatin (n?=?72) vs. placebo (n?=?75) in a population of HIV-infected subjects on stable antiretroviral therapy with LDL-cholesterol 130?mg/dl or less (?3.36?mmol/l) and evidence of heightened T-cell activation (CD8CD38HLA-DR ?19%) or increased inflammation [high sensitivity C-reactive protein ?2?mg/l (?19?mmol/l)]. Change in common carotid artery intima-media thickness (IMT) (CCA-IMT) was the primary outcome. Secondary outcomes were changes in LDL and coronary artery calcium.Median (Q1, Q3) age was 46 (40, 53) years; 78% were man and 68% African-American; 49% were on a protease inhibitor. Mean (95% confidence interval) change in LDL was -21 (-27 to -15)?mg/dl [-0.54 (-0.70 to -0.39)?mmol/l] in the rosuvastatin arm. In a multivariable linear mixed-effects model, assignment to statin was associated with 0.019?mm (95% confidence interval: 0.002-0.037?mm) less progression of CCA-IMT over 96 weeks. We did not find substantial effect modification by level of inflammation or immune activation biomarkers, except for a borderline statistically significant interaction for soluble vascular cell adhesion molecule (P?=?0.065). There was no difference in coronary artery calcium change (P?=?0.61).Rosuvastatin effectively lowers LDL and appears to substantially slow progression of CCA-IMT in patients with treated HIV infection. Future study is needed to determine whether subjects with higher levels of inflammation or immune activation derive greater cardiovascular benefit from statin therapy.
| S-EPMC5007142 | biostudies-literature