Persistence of Association Between HIV and Risk of Atherosclerotic Cardiovascular Disease (1/20)

Christopher J. Hoffmann, MD, MPH, Johns Hopkins University School of Medicine

People with HIV are at increased risk for atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction (MI) and stroke [Schouten J, et al. Clin Infect Dis. 2014;59(12):1787-1797Shah ASV, et al. Circulation. 2018;138(11):1100-1112]. Both untreated HIV and specific HIV treatment regimens have been associated with ASCVD. Earlier initiation of antiretroviral therapy (ART) and a shift away from regimens associated with ASCVD may change the ASCVD risk profile for people with HIV. Rosenson and colleagues assessed the association between HIV and ASCVD, including MI, stroke, and lower-limb artery disease events among a contemporary cohort of people being treated with antiretroviral medications [Rosenson RS, et al. J Am Heart Assoc. 2020;9(1):e013744].

The investigators assembled a retrospective cohort of people with HIV and matched controls using the MarketScan database of administrative and claims data from employer-sponsored healthcare plans and Medicare supplemental plans. From January 1, 2011, to December 31, 2016, individuals with either ≥1 hospitalization with a discharge diagnosis of HIV or ≥2 pharmacy claims for ART were included. Individuals aged ≤19 years living in the United States for <1 year before being identified as having HIV in the database who did not have continuous healthcare coverage were excluded. Four individuals without HIV were frequency matched to each individual with HIV based on age group, sex, and calendar year in which the HIV diagnosis was entered in the database.

In addition to HIV status, age, and sex, the following patient-level data were abstracted from the MarketScan database: history of coronary artery disease, stroke, peripheral artery disease, diabetes, heart failure, chronic kidney disease, liver disease, or depression; receipt of care from a cardiologist; hospitalization; tobacco use; and use of antihypertensive, statin, and nonstatin lipid-lowering medications. Use of ART was defined as >2 prescription fills within 1 year before each individual’s index date for HIV classification. Individuals were followed from the index date until December 31, 2016, for hospitalizations for ASCVD. The investigators used Cox proportional models, including adjusting for potential confounders, to compare ASCVD outcomes between the people with HIV and matched controls.

A total of 82,426 people with HIV and 329,704 matched controls met the inclusion criteria. Slightly more than 40% entered observation in 2011 and were between ages 19 and 44 years (42.6%). A larger proportion of people with HIV had a history of chronic kidney disease, liver disease, depression, antihypertensive medication use, statin use, tobacco use, and polypharmacy. Of people with HIV, 50.2% were receiving nucleoside reverse transcriptase inhibitors, 44.2% were receiving nonnucleoside reverse transcriptase inhibitors, 22.1% were receiving protease inhibitors, and 21.7% were receiving other antiretroviral medications (e.g., integrase strand transferase inhibitors, entry inhibitors, pharmacokinetic enhancers).

During a median follow-up of 1.6 years, 3,287 ASCVD events were identified in the database. The hazard for composite ASCVD was higher among people with HIV (hazard ratio, 1.29; 95% confidence interval, 1.18-1.40) than those without HIV. The hazard was also higher for MI, stroke, and lower-limb arterial disease for people with HIV. The use of statins reduced the hazard of each outcome among people with HIV, although the hazard trend remained higher among people with HIV. When adjusting ASCVD events by characteristics, the hazard was highest among individuals aged 19 to 44 years compared with matched individuals without HIV, suggesting an interaction between age and HIV and the hazard of ASCVD. No characteristics (e.g., statin use) negated the increased hazard for ASCVD among people with HIV.

This study suggests that people with HIV who are in care now or were in the past few years are at higher risk for ASCVD than age- and sex-matched controls. The finding of the highest risk among individuals aged 19 to 44 years is notable because this population is likely to have been diagnosed with HIV recently and have initiated ART soon after diagnosis with the contemporary ART regimens that are less likely to cause atherosclerosis than older regimens. The results of this study suggest the persistence of ASCVD risk even among individuals recently infected with HIV and started on ART.

ASCVD risk reduction includes the use of statins as well as an overall reduction in cholesterol, blood pressure control, smoking cessation, and HIV virologic suppression. The investigators did not include laboratory data, blood pressure measurements, or prior ART history, and controlling for these might have reduced the effect size of the observed association between HIV and ASCVD. In addition, this study was not designed to assess for an association between ASCVD and HIV among people with HIV initiated on rapid ART with regimens not believed to be associated with atherosclerosis. Another limitation is that the causes of stroke and MI were not assessed to differentiate between atherosclerotic and non-atherosclerotic events (i.e., type 2 MI). A higher proportion of non-atherosclerotic events among people with HIV may partly explain the association found by the investigators, and this could be the reason for a larger association effect size among those aged 19 to 44 years. Despite these limitations, this study provides a reminder to optimize ASCVD management among people with HIV.