Changes in Body Mass Index with Longer-term Integrase Inhibitor Use: A Longitudinal Analysis of Data from the Randomized Trial to Prevent Vascular Events in Human Immunodeficiency Virus (REPRIEVE).
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SUBMITTER: Kileel EM
PROVIDER: S-EPMC10474926 | biostudies-literature | 2023 Jun
REPOSITORIES: biostudies-literature
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Changes in Body Mass Index with Longer-term Integrase Inhibitor Use: A Longitudinal Analysis of Data from the Randomized Trial to Prevent Vascular Events in Human Immunodeficiency Virus (REPRIEVE).
Kileel Emma M EM Malvestutto Carlos D CD Lo Janet J Fitch Kathleen V KV Fichtenbaum Carl J CJ Aberg Judith A JA Zanni Markella V MV Martinez Esteban E Okeke Nwora Lance NL Kumar Princy P Joao Esau E Bares Sara H SH Berrner Daniel D Smieja Marek M Roa Jhoanna C JC McCallum Sara S Douglas Pamela S PS Ribaudo Heather J HJ Grinspoon Steven K SK
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20230601 11
Over 2-years of follow-up, integrase strand transfer inhibitor (INSTI)-use was associated with weight gain among those on an INSTI <2 years at entry (+0.27 kg/m2/year; 95% confidence interval [CI], .22 to .33 vs +0.17 kg/m2/year; 95% CI, .12 to .23; P = .01), but not those on an entry INSTI >2 years. ...[more]
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Project description:BackgroundCardiovascular disease (CVD) is more frequent among people with HIV (PWH) and may relate to traditional and nontraditional factors, including inflammation and immune activation. A critical need exists to develop effective strategies to prevent CVD in this population.MethodsThe Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) (A5332) is a prospective, randomized, placebo-controlled trial of a statin strategy for the primary prevention of major adverse cardiovascular events (MACE) in PWH with low to moderate traditional risk. At least 7,500 PWH, 40-75 years of age, on stable antiretroviral therapy, will be randomized to pitavastatin calcium (4 mg/d) or identical placebo and followed for up to 8 years. Participants are enrolled based on the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) risk score and low-density lipoprotein cholesterol (LDL-C) level with a goal to identify a low- to moderate-risk population who might benefit from a pharmacologic CVD prevention strategy. Potential participants with a risk score ≤ 15% were eligible based on decreasing LDL-C thresholds for increasing risk score >7.5% (LDL-C <190 mg/dL for risk score <7.5%, LDL-C <160 mg/dL for risk score 7.6%-10%, and LDL-C<130 mg/dL for risk score 10.1%-15%). The primary objective is to determine effects on a composite end point of MACE. Formal and independent adjudication of clinical events will occur using standardized criteria. Key secondary end points include effects on MACE components, all-cause mortality, specified non-CVD events, AIDS and non-AIDS events, and safety.ResultsTo date, REPRIEVE has enrolled >7,500 participants at approximately 120 sites across 11 countries, generating a diverse and representative population of PWH to investigate the primary objective of the trial.ConclusionsREPRIEVE is the first trial investigating a primary CVD prevention strategy in PWH. REPRIEVE will inform the field of the efficacy and safety of a statin strategy among HIV-infected participants on antiretroviral therapy and provide critical information on CVD mechanisms and non-CVD events in PWH.
| S-EPMC6535121 | biostudies-literature
Project description:BackgroundPeople with HIV (PWH) are at increased risk of cardiovasvular disease (CVD) and sudden cardiac death. Previous work has suggested an association between HIV infection and electrocardiographic (ECG) abnormalities. There are limited data on the burden of ECG abnormalities among PWH in a multiracial, multiethnic globally representative population.SettingOne hundred twenty sites in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE).MethodsECG findings were grouped into clinically relevant categories using sex-specific thresholds when indicated. We used the Fisher exact tests to assess associations of demographic characteristics and ECG abnormalities. We used logistic regression model to assess associations between demographic and HIV management measures, with adjustment.ResultsWe analyzed data for 7720 PWH (99% of participants) (median age 50 years, 69% male participants). There were 3346 (43%) Black or African American, 2680 (35%) White, and 1139 (15%) Asian participants. Most of the participants (97%) had viral load that was <400 copies/mL or <lower limits of quantification. Nearly half of the participants had at least one ECG abnormality (44%). QTc prolongation was more common among male than female participants (9% vs. 6%, P = 0.001) and nearly twice as common among Asian participants (12%) when compared with other racial groups (7%) (P < 0.0001). Participants with viral load >400 copies/mL had approximately twice the odds of prolonged QTc compared with those that were undetectable (adjusted OR: 2.05, 95% CI: 1.22 to 3.45).ConclusionsProlonged QTc is common among male, Asian, and REPRIEVE participants with higher viral loads. These relationships warrant future investigation of linkages to ensuing CVD events among PWH.
| S-EPMC8837824 | biostudies-literature
Project description:BACKGROUND:People with HIV (PWH) have increased cardiovascular events, inflammation, and high-risk coronary atherosclerosis. Statin therapy has been shown to lower the risk of cardiovascular disease (CVD) in the general population, but whether this results from reductions in coronary atherosclerosis and is mediated by decreased inflammation remains unknown. METHODS:REPRIEVE is a randomized, placebo-controlled trial of pitavastatin calcium (4 mg/day) vs. placebo enrolling at least 7500 PWH between 40-75 years, on antiretroviral therapy (ART), with low to moderate traditional CVD risk. The Mechanistic Substudy of REPRIEVE (A5333s) is co-enrolling 800 participants from 31 US sites. These participants undergo serial contrast enhanced coronary computed tomography angiography (CCTA) and measurements of biomarkers of inflammation and immune activation at baseline and after 2 years of follow-up. The primary objectives are to determine the effects of pitavastatin on noncalcified coronary atherosclerotic plaque (NCP) volume, low attenuation plaque, and positive remodeling and on changes in immune activation and inflammation and to assess relationships between the two. Changes in CAD will be assessed in a standardized fashion by a core lab with expert readers blinded to time points and participant information; immune activation and inflammation assessment is also performed centrally. RESULTS:To date the Mechanistic Substudy has completed planned enrollment, with 805 participants. CONCLUSION:This study represents the first large, randomized, CCTA-based assessment of the effects of a primary prevention strategy for CVD on high-risk CAD, immune activation and inflammation among PWH. The study will assess pitavastatin's effects on coronary plaque, and the interrelationship of these changes with biomarkers of immune activation and inflammation in PWH to determine mechanisms of CVD prevention and improved outcomes in this population.
| S-EPMC6596304 | biostudies-literature
Project description:BackgroundEmerging data demonstrate that the use of integrase inhibitor (INSTI)-based antiretroviral treatment (ART) is associated with increased weight, but the cardiometabolic health consequences of increased weight remains poorly understood.MethodsThis analysis examined INSTI use (>6 months) at entry among REPRIEVE participants enrolled in High Income and Latin America/Caribbean Global Burden of Disease regions. Primary analyses used linear and logistic regression; secondary analyses used quantile regression to examine differences across the full data distribution. Characteristics of those with and without INSTI use were balanced using inverse probability of treatment weighting.ResultsAmong 4500 REPRIEVE participants, 1848 were on an INSTI-based regimen at entry for an average of 2.1 ± 1.8 years. Integrase inhibitor use (vs no INSTI use) was associated with higher odds of obesity (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.4-1.9) and higher mean body mass index ([BMI] +1.5kg/m2; 95% CI, 1.0-1.9) and waist circumference (+3.6cm; 95% CI, 2.6-4.6). Differences in weight related to INSTI use were greater in the upper tails of the distribution (+3.1kg/m2 [95% CI, 1.9-4.4] at the 90th centile vs +0.7kg/m2 [95% CI, 0.2-1.2] at the 50th centile) and among women and nonwhite participants, with sex and race having an additive effect on BMI. Conversely, INSTI use was not associated with differences in glucose, low-density lipoprotein cholesterol, or higher odds of metabolic syndrome or hypertension.ConclusionsDifferences in weight and waist circumference associated with INSTI use are (1) not uniform across people with human immunodeficiency virus, (2) greatest among women and nonwhites, and (3) concentrated at the upper tails of weight distribution. These data identify at-risk subgroups for whom long-term cardiovascular disease outcomes should be carefully assessed.
| S-EPMC8651160 | biostudies-literature
Project description:BackgroundIntegrase strand transfer inhibitors (INSTIs) have been associated with an increased risk for cardiovascular disease (CVD) events. We investigated the impact of starting INSTI-based antiretroviral therapy (ART) on CVD events among treatment-naïve people with human immunodeficiency virus using a target trial framework, which reduces the potential for confounding and selection bias.MethodsWe included Swiss HIV Cohort Study participants who were ART-naïve after May 2008, when INSTIs became available in Switzerland. Individuals were categorized according to their first ART regimen (INSTI vs other ART) and were followed from ART start until the first of CVD event (myocardial infarction, stroke, or invasive cardiovascular procedure), loss to follow-up, death, or last cohort visit. We calculated hazard ratios and risk differences using pooled logistic regression models with inverse probability of treatment and censoring weights.ResultsOf 5362 participants (median age 38 years, 21% women, 15% of African origin), 1837 (34.3%) started INSTI-based ART, and 3525 (65.7%) started other ART. Within 4.9 years (interquartile range, 2.4-7.4), 116 CVD events occurred. Starting INSTI-based ART was not associated with an increased risk for CVD events (adjusted hazard ratio, 0.80; 95% confidence interval [CI], .46-1.39). Adjusted risk differences between individuals who started INSTIs and those who started other ART were -0.17% (95% CI, -.37 to .19) after 1 year, -0.61% (-1.54 to 0.22) after 5 years, and -0.71% (-2.16 to 0.94) after 8 years.ConclusionsIn this target trial emulation, we found no difference in short- or long-term risk for CVD events between treatment-naïve people with human immunodeficiency virus who started INSTI-based ART and those on other ART.
| S-EPMC10495132 | biostudies-literature
Project description:ObjectiveTo investigate the longitudinal associations between active commuting (walking and cycling to work) and body mass index (BMI).MethodWe used self-reported data on height, weight and active commuting from the Commuting and Health in Cambridge study (2009 to 2012; n=809). We used linear regression to test the associations between: a) maintenance of active commuting over one year and BMI at the end of that year; and b) change in weekly time spent in active commuting and change in BMI over one year.ResultsAfter adjusting for sociodemographic variables, other physical activity, physical wellbeing and maintenance of walking, those who maintained cycle commuting reported a lower BMI on average at one year follow-up (1.14kg/m(2), 95% CI: 0.30 to 1.98, n=579) than those who never cycled to work. No significant association remained after adjustment for baseline BMI. No significant associations were observed for maintenance of walking. An increase in walking was associated with a reduction in BMI (0.32kg/m(2), 95% CI: 0.03 to 0.62, n=651, after adjustment for co-variates and baseline BMI) only when restricting the analysis to those who did not move. No other significant associations between changes in weekly time spent walking or cycling on the commute and changes in BMI were observed.ConclusionsThis work provides further evidence of the contribution of active commuting, particularly cycling, to preventing weight gain or facilitating weight loss. The findings may be valuable for employees choosing how to commute and engaging employers in the promotion of active travel.
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Project description:Normal and diseased human tissues were profiled for gene expression using the Affymetrix U133 plus 2.0 array In total 677 samples were processed , representing over 90 distinct tissue types Some tissue samples were purchased from Stratagene (SG), Ambion (AB), and Becton-Dickinson (BD) Keywords: Human body index of gene expression
2007-04-09 | GSE7307 | GEO
Project description:The relationship between body mass index (BMI) with mortality risk, in particular the BMI category associated with the lowest all-cause and CVD-and-stroke mortality and the BMI threshold for defining overweight or obesity in older persons is controversial. This study investigated the age-dependent associations of BMI categories with all-cause and cardiovascular disease (CVD) and stroke mortality.Prospective cohort study (Singapore Longitudinal Ageing Studies) of older adults aged 55 and above, followed up from 2003 to 2011. Participants were 2605 Chinese with baseline BMI and other variables. Outcome Measurement: Mortality hazard ratios (HR) for all-cause and CVD and stroke mortality.Overall, BMI showed a U-shaped relationship with all-cause and CVD and stroke mortality, being lowest at Normal Weight-II category (BMI 23.0-24.9 kg/m2). Most evidently among the middle-aged (55-64 years), all-cause mortality risks relative to Normal Weight-II were elevated for underweight (<BMI 18.5; HR = 4.92, p<0.0138), Normal Weight-I (BMI 18.5-22.9; HR = 3.41, p = 0.0149), and Overweight-Obese (BMI>30.0; HR = 4.05,p = 0.0423). Among the old (≥65 years), however, Overweight and Obese categories were not significantly associated with increased all-cause mortality (HR from 0.98 to 1.29), but Overweight-Obese was associated with increased CVD and stroke mortality (HR = 10.0, p = 0.0086).BMI showed a U-shaped relationship with mortality. Among older persons aged 65 and above, the overweight-or-obese category of BMI was not associated with excess all-cause mortality.
| S-EPMC5524359 | biostudies-other
Project description:BackgroundPeople with human immunodeficiency virus (PWH) face increased risks for heart failure and adverse heart failure outcomes. Myocardial steatosis predisposes to diastolic dysfunction, a heart failure precursor. We aimed to characterize myocardial steatosis and associated potential risk factors among a subset of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) participants.MethodsEighty-two PWH without known heart failure successfully underwent cardiovascular magnetic resonance spectroscopy, yielding data on intramyocardial triglyceride (IMTG) content (a continuous marker for myocardial steatosis extent). Logistic regression models were applied to investigate associations between select clinical characteristics and odds of increased or markedly increased IMTG content.ResultsMedian (Q1, Q3) IMTG content was 0.59% (0.28%, 1.15%). IMTG content was increased (> 0.5%) among 52% and markedly increased (> 1.5%) among 22% of participants. Parameters associated with increased IMTG content included age (P = .013), body mass index (BMI) ≥ 25 kg/m2 (P = .055), history of intravenous drug use (IVDU) (P = .033), and nadir CD4 count < 350 cells/mm³ (P = .055). Age and BMI ≥ 25 kg/m2 were additionally associated with increased odds of markedly increased IMTG content (P = .049 and P = .046, respectively).ConclusionsA substantial proportion of antiretroviral therapy-treated PWH exhibited myocardial steatosis. Age, BMI ≥ 25 kg/m2, low nadir CD4 count, and history of IVDU emerged as possible risk factors for myocardial steatosis in this group.Clinical trials registrationNCT02344290; NCT03238755.
| S-EPMC7347082 | biostudies-literature
Project description:BackgroundChronic kidney disease is a common comorbid condition among persons living with human immunodeficiency virus (PWH). We characterized baseline kidney function in the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) trial cohort.MethodsREPRIEVE enrolled PWH with low to moderate cardiovascular risk based on traditional risk factors to evaluate the effect of statin therapy on cardiovascular events. We determined baseline estimated glomerular filtration rate (eGFR) with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease, and Cockcroft-Gault equations, and we evaluated baseline factors associated with eGFR <90 mL/min/1.73 m2 by logistic regression. We performed Bland-Altman plots and scatterplots to assess agreement between equations.ResultsAmong 7770 participants enrolled, the median age was 50 years, 31% were female (natal sex), 43% black or African American and 15% Asian, the median body mass index (calculated as calculated as weight in kilograms divided by height in meters squared) was 25.8, and the median CD4 cell count 620/µL. The median CKD-EPI eGFR was 97 mL/min/1.73 m2, and 38% had an eGFR <90 mL/min/1.73 m2. In the adjusted model, factors associated with eGFR <90 mL/min/1.73 m2 included white race, older age, higher body mass index, high-income region of enrollment, hypertension, and tenofovir disoproxil fumarate. The CKD-EPI and Modification of Diet in Renal Disease equations demonstrated strong agreement, particularly at lower eGFR values. Overall, there was 56% concordance between the 3 equations (categories <60, 60 to <90, ≥90 mL/min), improving to 73% after accounting for individual body surface area.ConclusionsREPRIEVE enrolled a diverse cohort including a substantial number of PWH with reduced kidney function. Factors associated with reduced eGFR included traditional risk factors and tenofovir disoproxil fumarate exposure. Three commonly used equations have only fair agreement, with potential implications for both clinical care and epidemiologic studies.Clinical trials registrationNCT02344290.
| S-EPMC7347080 | biostudies-literature