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

Abstract

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 ± 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.

Change in body weight and risk of hypertension after switching from efavirenz to dolutegravir in adults living with HIV: evidence from routine care in Johannesburg, South Africa

“…Prior literature has also demonstrated potential differential effects of INSTIs on weight gain among men and women. 21 , 22 In the NAMSAL study, women were more likely to experience a ≥10% change in weight over 48-week follow-up period compared to men. 23 In a multinational cohort of adults with well-controlled HIV, women on dolutegravir had a higher mean BMI and waist circumference than did women on an alternative ART regimen or men on dolutegravir.…”

Virological outcomes and metabolic effects after switching from ritonavir-boosted protease inhibitors to a dolutegravir-based regimen in virologically suppressed patients living with HIV

“…26 Previous studies have shown INSTI-based regimens to be associated with increased waist circumference, but not to a statistically significant extent. 27–29 The statistically significant increase in waist circumference found in our study may have been due to our participants being older with more coexistent medical conditions including diabetes, CKD, and dyslipidemia. 29 However, the magnitude of the change was too small to be concerning.…”

A clinical review of HIV integrase strand transfer inhibitors (INSTIs) for the prevention and treatment of HIV-1 infection

“…Some studies have shown an association between ARV-related weight gain and/or body mass index changes and certain populations such as women and Black and Hispanic populations. However, further study is warranted to understand both of what predictors, if any, exist for this phenomenon, as well as the cardiovascular and metabolic implications associated with weight gain [13,[125][126][127][128][129][130].…”