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  AIDS 2022
July 29 - Aug 2
24th Intl AIDS Conference
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Incidence of cardiometabolic outcomes among people living with HIV initiated on INSTI versus non-INSTI antiretroviral therapies
Integrase Inhibitor in First ART Poses Some Cardio Risks in Big US Analysis

  AIDS 2022, July 29-August 2, Montreal
Mark Mascolini
After fewer than 2 years of follow-up in a relatively young US HIV population, people starting antiretroviral therapy (ART) with an integrase inhibitor (INSTI) ran a higher risk of congestive heart failure, myocardial infarction (MI), and lipid disorders than people starting a non-INSTI regimen [1]. But this analysis of a 14,000-person compilation of health insurance databasesa found no difference between the INSTI group and the non-INSTI group in having one or more cardiometabolic outcomes, one or more cardiovascular outcomes, or one or more metabolic outcomes.
US and other HIV treatment guidelines call for an INSTI in first-line ART combinations. Although some research links INSTIs to higher risk of weight gain and increased blood pressure and hemoglobin A1c (a diabetes signal), whether initial treatment with an INSTI heightens risk of specific newly diagnosed cardiometabolic conditions remained uncertain until this analysis by researchers at Vanderbilt University and Janssen Scientific Affairs.
To address this question, the Vanderbilt/Janssen team conducted a retrospective longitudinal cohort study using data from IBM MarketScan Commercial Claims and Encounters, Medicare Supplemental, and Multi-State Medicaid insurance claims databases from August 2012 to January 2021. The index date (starting point) for the analysis was the day a person started a first INSTI or non-INSTI combination. Follow-up continued until a person switched to a new HIV drug outside the index regimen class, 90 days after a person stopped the index drug class, the end of insurance eligibility, or the day data became unavailable.
The researchers used inverse probability of treatment weights to create an INSTI group and a non-INSTI group that matched each other in age, sex, race, geographic region, type of insurance, index date calendar year, and other variables. They ended up with 7059 people in the INSTI group and 7017 in the non-INSTI group, which had average index date ages of 38.6 and 39.0, a similar proportion of women (23.2% and 23.9%), similar proportions by race or ethnicity, similar US geographic locations, and similar insurance plans (69.4% and 69.9% commercial only; 29.7% and 29.2% Medicaid only; similar tiny rates of commercial plus Medicare insurance and Medicare only). About one third in the INSTI group and the non-INSTI group (36.5%) started an HIV drug linked to weight gain, while about 9% started a drug linked to weight loss.
Follow-up averaged 1.5 years in INSTI takers and 1.1 years in non-INSTI takers. Multivariable weighted Cox proportional hazards models determined that people starting ART with an INSTI were twice as likely to get diagnosed with congestive heart failure during follow-up (adjusted hazard ratio [aHR] 2.12, 95% confidence interval [CI] 1.08 to 4.05, P = 0.036), about 75% more likely to suffer a new MI (aHR 1.79, 95% CI 1.03 to 5.65, P = 0.036), and about 25% more likely to have a new lipid disorder (aHR 1.26, 95% CI 1.04 to 1.58, P = 0.020).
But this same type of analysis found no difference between INSTI-starters and non-INSTI-starters in likelihood of having 1 or more cardiometabolic outcomes, 1 or more cardiovascular outcomes, 1 or more metabolic outcomes, or other individual cardiometabolic outcomes assessed (stroke/transient ischemic attack, coronary artery disease, lipodystrophy, metabolic syndrome, type 2 diabetes, hypertension).
The Vanderbilt/Janssen group stressed the importance of picking a first-line antiretroviral regimen with a low risk of age-related cardiometabolic conditions that pose a greater risk as HIV populations age. To determine the validity of their findings, the researchers called for further study with additional clinical variables and longer follow-up.
1. Rebeiro PF, Emond B, Rossi C, et al. Incidence of cardiometabolic outcomes among people living with HIV initiated on INSTI versus non-INSTI antiretroviral therapies. AIDS 2022, July 29-August 2, Montreal. Abstract EPB108.
bear in mind Atazanavir/r has been shown to be cardioprotective. jules