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.

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.

Cost-effectiveness analysis of UGT1A1 genetic testing to inform antiretroviral prescribing in HIV disease.

BACKGROUND: Homozygosity for UGT1A1*28/*28 has been reported to be associated with atazanavir-associated hyperbilirubinaemia and premature atazanavir discontinuation. We assessed the potential cost-effectiveness of UGT1A1 testing to inform the choice of an initial protease-inhibitor-containing regimen in antiretroviral therapy (ART)-naive individuals. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications computer simulation model to project quality-adjusted life years (QALYs) and lifetime costs (2009 USD) for atazanavir-based ART with or without UGT1A1 testing, using darunavir rather than atazanavir when indicated. We assumed the UGT1A1-associated atazanavir discontinuation rate reported in the Swiss HIV Cohort Study (a *28/*28 frequency of 14.9%), equal efficacy and cost of atazanavir and darunavir and a genetic assay cost of $107. These parameters, as well as the effect of hyperbilirubinaemia on quality of life and loss to follow up, were varied in sensitivity analyses. Costs and QALYs were discounted at 3% annually. RESULTS: Initiating atazanavir-based ART at CD4(+) T-cell counts <500 cells/µl without UGT1A1 testing had an average discounted life expectancy of 16.02 QALYs and $475,800 discounted lifetime cost. Testing for UGT1A1 increased QALYs by 0.49 per 10,000 patients tested and was not cost-effective (>$100,000/QALY). Testing for UGT1A1 was cost-effective (<$100,000/QALY) if assay cost decreased to $10, or if avoiding hyperbilirubinaemia by UGT1A1 testing reduced loss to follow-up by 5%. If atazanavir and darunavir differed in cost or efficacy, testing for UGT1A1 was not cost-effective under any scenario. CONCLUSIONS: Testing for UGT1A1 may be cost-effective if assay cost is low and if testing improves retention in care, but only if the comparator ART regimens have the same drug cost and efficacy.