Diet in a global cohort of adults with HIV at low-to-moderate traditional cardiovascular disease risk.

OBJECTIVE: To characterize diet quality across a global cohort of people with HIV (PWH). DESIGN: Cross-sectional analysis. METHODS: Leveraging REPRIEVE data from baseline across five Global Burden of Disease (GBD) regions, we analyzed participant responses to the Rapid Eating Assessment for Participants questionnaire. An overall diet quality score and scores for specific diet components were generated. Higher scores indicate better diet quality. RESULTS: Among 7736 participants (median age 50 years, 30% women, median BMI 25.8 kg/m 2 ) overall diet quality score (max score 30) was optimal in 13% of participants and good, suboptimal or poor in 45%, 38%, and 4% of participants, respectively; saturated fat score (max score 18) was good, suboptimal, or poor in 38%, 40%, or 7% of participants, respectively. Diet quality scores differed across GBD region with the highest scores reported in the South Asia region [median 23 (21-25)] and lowest in the sub-Saharan Africa region [median 15 (12-18)]; 61% of participants in the South Asia region reported optimal diet quality compared with only 6% in the sub-Saharan Africa region. Higher atherosclerotic cardiovascular risk scores were seen with worsening diet quality. CONCLUSION: Among PWH eligible for primary CVD prevention, diet quality was suboptimal or poor for almost half of participants, and there were substantial variations in diet quality reported by GBD region. TRIAL REGISTRATION: NCT02344290.

Assessment of Obesity and Cardiometabolic Status by Integrase Inhibitor Use in REPRIEVE: A Propensity-Weighted Analysis of a Multinational Primary Cardiovascular Prevention Cohort of People With Human Immunodeficiency Virus.

BACKGROUND: Emerging 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. METHODS: This 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. RESULTS: Among 4500 REPRIEVE participants, 1848 were on an INSTI-based regimen at entry for an average of 2.1 ±â€…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. CONCLUSIONS: Differences 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.

Assessment of Coronary Artery Disease With Computed Tomography Angiography and Inflammatory and Immune Activation Biomarkers Among Adults With HIV Eligible for Primary Cardiovascular Prevention.

Importance: Cardiovascular disease (CVD) is increased among people with HIV (PWH), but little is known regarding the prevalence and extent of coronary artery disease (CAD) and associated biological factors in PWH with low to moderate traditional CVD risk. Objectives: To determine unique factors associated with CVD in PWH and to assess CAD by coronary computed tomography angiography (CTA) and critical pathways of arterial inflammation and immune activation. Design, Setting, and Participants: This cohort study among male and female PWH, aged 40 to 75 years, without known CVD, receiving stable antiretroviral therapy, and with low to moderate atherosclerotic cardiovascular disease (ASCVD) risk according to the 2013 American College of Cardiology/American Heart Association pooled cohort equation, was part of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among PWH conducted at 31 US sites. Participants were enrolled from May 2015 to February 2018. Data analysis was conducted from May to December 2020. Exposure: HIV disease. Main Outcomes and Measures: The primary outcome was the prevalence and composition of CAD assessed by coronary CTA and, secondarily, the association of CAD with traditional risk indices and circulating biomarkers, including insulin, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL) 6, soluble CD14 (sCD14), sCD163, lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), and high-sensitivity C-reactive protein (hsCRP). Results: The sample included 755 participants, with a mean (SD) age of 51 (6) years, 124 (16%) female participants, 267 (35%) Black or African American participants, 182 (24%) Latinx participants, a low median (interquartile range) ASCVD risk (4.5% [2.6%-6.8%]), and well-controlled viremia. Overall, plaque was seen in 368 participants (49%), including among 52 of 175 participants (30%) with atherosclerotic CVD (ASCVD) risk of less than 2.5%. Luminal obstruction of at least 50% was rare (25 [3%]), but vulnerable plaque and high Leaman score (ie, >5) were more frequently observed (172 of 755 [23%] and 118 of 743 [16%], respectively). Overall, 251 of 718 participants (35%) demonstrated coronary artery calcium score scores greater than 0. IL-6, LpPLA2, oxLDL, and MCP-1 levels were higher in those with plaque compared with those without (eg, median [IQR] IL-6 level, 1.71 [1.05-3.04] pg/mL vs 1.45 [0.96-2.60] pg/mL; P = .008). LpPLA2 and IL-6 levels were associated with plaque in adjusted modeling, independent of traditional risk indices and HIV parameters (eg, IL-6: adjusted odds ratio, 1.07; 95% CI, 1.02-1.12; P = .01). Conclusions and Relevance: In this study of a large primary prevention cohort of individuals with well-controlled HIV and low to moderate ASCVD risk, CAD, including noncalcified, nonobstructive, and vulnerable plaque, was highly prevalent. Participants with plaque demonstrated higher levels of immune activation and arterial inflammation, independent of traditional ASCVD risk and HIV parameters.

Leveraging a Landmark Trial of Primary Cardiovascular Disease Prevention in Human Immunodeficiency Virus: Introduction From the REPRIEVE Coprincipal Investigators.

The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) is the largest study of cardiovascular disease in human immunodeficiency virus. Enrolling 7770 participants from 2015 to 2019 with sites across 5 continents, REPRIEVE will assess the effects of a statin as a cardiovascular disease prevention strategy in people with HIV (PWH) receiving antiretroviral therapy (ART). Although the primary purpose of REPRIEVE, and its substudy assessing coronary plaque, is to assess cardiovascular outcomes, the trial is a rich source of data on population characteristics and critical comorbidities in PWH, particularly across Global Burden of Disease (GBD) regions, reflective of the ethnic, racial, and gender diversity in this global epidemic. The purpose of this Supplement is to leverage the rich phenotyping in REPRIEVE, to provide data on detailed patterns of baseline ART and immune function by GBD region, reproductive aging among cisgender women, and data on the participation and clinical characteristics of transgender participants. We also leveraged REPRIEVE to assess critical comorbidities, including renal dysfunction, muscle function and frailty, and myocardial steatosis. REPRIEVE is a remarkable collaboration between funders, trial networks, clinical research sites, clinical and data coordinating centers, and willing participants who devoted their time to make the trial possible.

Epidemiology of ischemic heart disease in HIV.

PURPOSE OF REVIEW: The purpose of this review is to summarize and synthesize recent data on the risk of ischemic heart disease (IHD) in HIV-infected individuals. RECENT FINDINGS: Recent studies in the field demonstrate an increasing impact of cardiovascular disease (CVD) on morbidity and mortality in HIV relative to AIDS-related diagnoses. Studies continue to support an approximately 1.5 to two-fold increased risk of IHD conferred by HIV, with specific risk varying by sex and virologic/immunologic status. Risk factors include both traditional CVD risk factors and novel, HIV-specific factors including inflammation and immune activation. Specific antiretroviral therapy (ART) drugs may increase CVD risk, yet the net effect of ART with viral suppression is beneficial with regard to CVD risk. Management of cardiovascular risk and prevention of CVD is complex, because current general population strategies target traditional CVD risk factors only. Extensive investigation is being directed at developing tailored CVD risk prediction algorithms and interventions to reduce CVD risk in HIV. SUMMARY: Increased IHD risk is a significant clinical and public health challenge in HIV. The development and application of HIV-specific interventions to manage CVD risk factors and reduce CVD risk will improve the long-term health of this ageing population.

Cost-effectiveness analysis of coronary artery disease screening in HIV-infected men.

BACKGROUND: HIV-infected patients are at increased risk of coronary artery disease (CAD). We evaluated the cost-effectiveness of cardiac screening for HIV-positive men at intermediate or greater CAD risk. DESIGN: We developed a lifetime microsimulation model of CAD incidence and progression in HIV-infected men. METHODS: Input parameters were derived from two HIV cohort studies and the literature. We compared no CAD screening with stress testing and coronary computed tomography angiography (CCTA)-based strategies. Patients with test results indicating 3-vessel/left main CAD underwent invasive coronary angiography (ICA) and received coronary artery bypass graft surgery. In the stress testing + medication and CCTA + medication strategies, patients with 1-2-vessel CAD results received lifetime medical treatment without further diagnostics whereas in the stress testing + intervention and CCTA + intervention strategies, patients with these results underwent ICA and received percutaneous coronary intervention. RESULTS: Compared to no screening, the stress testing + medication, stress testing + intervention, CCTA + medication, and CCTA + intervention strategies resulted in 14, 11, 19, and 14 quality-adjusted life days per patient and incremental cost-effectiveness ratios of 49,261, 57,817, 34,887 and 56,518 Euros per quality-adjusted life year (QALY), respectively. Screening only at higher CAD risk thresholds was more cost-effective. Repeated screening was clinically beneficial compared to one-time screening, but only stress testing + medication every 5 years remained cost-effective. At a willingness-to-pay threshold of 83,000 €/QALY (∼ 100,000 US$/QALY), implementing any CAD screening was cost-effective with a probability of 75-95%. CONCLUSIONS: Screening HIV-positive men for CAD would be clinically beneficial and comes at a cost-effectiveness ratio comparable to other accepted interventions in HIV care.

Decreased respiratory quotient in relation to resting energy expenditure in HIV-infected and noninfected subjects.

The purpose of this study was to evaluate the relationship of respiratory quotient (RQ), a surrogate marker of substrate oxidation, as well as body composition and dietary intake to resting energy expenditure (REE) among HIV-infected patients in the current era of highly active antiretroviral therapy and among non-HIV-infected control subjects. Resting energy expenditure is increased in HIV-infected patients; but little is known regarding the potential contribution of altered substrate metabolism, body composition, and dietary intake to increased energy expenditure in this population. Respiratory quotient, REE, body composition, and dietary intake parameters were assessed in 283 HIV-infected patients and 146 community-derived HIV-negative controls who were evaluated for metabolic studies between 1998 and 2005. Respiratory quotient was lower (0.83 +/- 0.00 vs 0.85 +/- 0.01, P = .005), whereas REE adjusted for fat-free mass (FFM) was higher (31.8 +/- 0.3 vs 29.8 +/- 0.3 kcal/[d kg], P < or = .0001), in HIV-infected compared with control subjects. In multivariate modeling among HIV-infected patients, including age, sex, and parameters of immune function, FFM (beta = 24.811334, P < .0001), visceral adiposity (beta = .7182746, P = .008), and total body fat (beta = 8.0506839, P = .041) were positively associated with REE, whereas RQ was negatively associated with REE (beta = -528.4808, P = .024). Overall r(2) was equal to 0.705 and P was less than .0001 for the model. In control subjects, by contrast, only visceral adiposity (beta = 1.0612073, P = .004), total body fat (beta = 15.805547, P = .010), and FFM (beta = 22.613005, P < .0001) were significant predictors of REE; and there was no relationship with RQ. Overall r(2) was equal to 0.825 and P was less than .0001 for the model. These data suggest that alterations in substrate metabolism may contribute to increased REE in HIV-infected patients compared with control subjects.