Association Between HIV Infection and the Risk of Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction in the Antiretroviral Therapy Era: Results From the Veterans Aging Cohort Study

Abstract

Importance: With improved survival, heart failure (HF) has become a major complication for individuals with human immunodeficiency virus (HIV) infection. It is unclear if this risk extends to different types of HF in the antiretroviral therapy (ART) era. Determining whether HIV infection is associated with HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), or both is critical because HF types differ with respect to underlying mechanism, treatment, and prognosis.

Objectives: To investigate whether HIV infection increases the risk of future HFrEF and HFpEF and to assess if this risk varies by sociodemographic and HIV-specific factors.

Design, setting, and participants: This study evaluated 98 015 participants without baseline cardiovascular disease from the Veterans Aging Cohort Study, an observational cohort of HIV-infected veterans and uninfected veterans matched by age, sex, race/ethnicity, and clinical site, enrolled on or after April 1, 2003, and followed up through September 30, 2012. The dates of the analysis were October 2015 to November 2016.

Exposure: Human immunodeficiency virus infection.

Main outcomes and measures: Outcomes included HFpEF (EF≥50%), borderline HFpEF (EF 40%-49%), HFrEF (EF<40%), and HF of unknown type (EF missing).

Results: Among 98 015 participants, the mean (SD) age at enrollment in the study was 48.3 (9.8) years, 97.0% were male, and 32.2% had HIV infection. During a median follow-up of 7.1 years, there were 2636 total HF events (34.6% were HFpEF, 15.5% were borderline HFpEF, 37.1% were HFrEF, and 12.8% were HF of unknown type). Compared with uninfected veterans, HIV-infected veterans had an increased risk of HFpEF (hazard ratio [HR], 1.21; 95% CI, 1.03-1.41), borderline HFpEF (HR, 1.37; 95% CI, 1.09-1.72), and HFrEF (HR, 1.61; 95% CI, 1.40-1.86). The risk of HFrEF was pronounced in veterans younger than 40 years at baseline (HR, 3.59; 95% CI, 1.95-6.58). Among HIV-infected veterans, time-updated HIV-1 RNA viral load of at least 500 copies/mL compared with less than 500 copies/mL was associated with an increased risk of HFrEF, and time-updated CD4 cell count less than 200 cells/mm3 compared with at least 500 cells/mm3 was associated with an increased risk of HFrEF and HFpEF.

Conclusions and relevance: Individuals who are infected with HIV have an increased risk of HFpEF, borderline HFpEF, and HFrEF compared with uninfected individuals. The increased risk of HFrEF can manifest decades earlier than would be expected in a typical uninfected population. Future research should focus on prevention, risk stratification, and identification of the mechanisms for HFrEF and HFpEF in the HIV-infected population.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Freiberg reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr DuVall reported receiving grants from the National Heart, Lung, and Blood Institute (NHLBI) during the conduct of the study and reported receiving grants from the following outside of the submitted work: AbbVie Inc, Amgen Inc, Anolinx LLC, Astellas Pharma Inc, AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim International GmbH, F. Hoffman-La Roche Ltd, Genentech Inc, Genomic Health, Inc, Gilead Sciences Inc, GlaxoSmithKline plc, HITEKS Solutions Inc, Innocrin Pharmaceuticals Inc, Kantar Health, LexisNexis Risk Solutions, Merck & Co, Inc, Mylan Specialty LP, Myriad Genetics, Inc, Northrop Grumman Information Systems, Novartis International AG, PAREXEL International Corporation, and Shire PLC. Dr Brandt reported receiving grants from the NHLBI during the conduct of the study and reported receiving grants from the NIH and the Department of Veterans Affairs outside of the submitted work. Dr So-Armah reported receiving grants from the NIH during the conduct of the study. Dr Gottlieb reported receiving grants from Novartis International AG outside of the submitted work. Dr Tracy reported receiving grants from the NIH outside of the submitted work. Dr Bedimo reported receiving grants and other compensation from Bristol-Myers Squibb and Merck & Co, Inc, and reported receiving other compensation from Theratechnologies, Inc, and Gilead Sciences Inc, all outside of the submitted work. Dr Brown reported receiving grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) during the conduct of the study. Dr Justice reported receiving grants from the NIAAA during the conduct of the study. Dr Butt reported receiving grants from Merck & Co, Inc, Gilead Sciences Inc, and AbbVie Inc, all outside of the submitted work. No other disclosures were reported.