Impact of HIV Infection and ART on Evolving Risks of Heart Failure

Patients with HIV have a significantly increased risk of heart failure (HF) of all kinds, but the risk of HF with reduced ejection fraction (HFrEF) is particularly high, according to the results of the Veterans Aging Cohort Study reported in JAMA Cardiology.¹

The investigators, led by Matthew Freiberg, MD, of the Vanderbilt University School of Medicine in Nashville, Tennessee, evaluated the entire cohort of 98,015 participants, including both HIV-infected and non-HIV-infected individuals enrolled from April 2003 to November 2016, all of whom were free of cardiovascular disease (CVD) at baseline. They found that the risk for HF with a preserved ejection fraction (HFpEF) higher than 50% and for borderline HFpEF with ranges from 40% to 50% were increased by 21% and 37%, respectively. The most striking finding, however, was a 61% increased risk for HFrEF (EF<40%) in HIV-infected individuals compared with normal controls.

A key observation from the study was that rates of total HF and HFrEF were most significantly increased in younger HIV-infected participants (younger than 40 at baseline) — decades earlier than increased similar risks were likely to be seen in uninfected individuals.

Of 2636 HF events recorded in the total cohort over a median follow-up of 7.1 years, the events by type were 34.6% HFpEF, 15.5% borderline HFpEF, 37.1% HFrEF, and 12.8% indeterminate. Total HF rates were significantly higher in both HIV-positive and HIV-infected participants compared with non-HIV-infected individuals. Use of antiretroviral therapy (ART) at baseline (73.9% of patients) was associated with an increased risk of HFpEF, suggesting a possible direct role of ART in HF. The investigators pointed to supportive research showing that despite early and effective viral suppression from ART, inflammation levels in HIV-infected individuals do not return to normal.²

HIV status was also a factor. Risks of HFrEF were increased with time-updated HIV-1 RNA loads ≥500 copies/mL compared with lower viral loads (median baseline HIV-1 RNA = 1357 copies/mL), as well as time-updated CD4 cell counts <200 cells/mm³ compared with ≥500 cells/mm³ (median baseline = 382cells/mm).³ Below normal CD4 cell counts also increased risks for HFpEF.

The researchers pointed to the success of ART in the evolution of CVD in the HIV-infected population as a consequence of longer lifespans. Therapeutic strategies in the management of CVD risk factors are now necessary in the long-term management of HIV-infected patients, as the disease poses higher risks of HF even at younger ages of infection, and 25% of all new cases in the United States occur in people between the age 13 and 24.³

References

1. Freiberg MS, Chang CH, Skanderson M, et al. 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 [published online April 5, 2017]. JAMA Cardiol. doi:10.1001/jamacardio.2017.0264
2. Freiberg MS, Bebu I, Tracy R, et al; Infectious Disease Clinical Research Program HIV Working Group. D-dimer levels before HIV seroconversion remain elevated even after viral suppression and are associated with an increased risk of non-AIDS events. PLoS One. 2016;11:e0152588. doi:10.1371/journal.pone.0152588
3. HIV/AIDS: risk by age group. Centers for Disease Control and Prevention. www.cdc.gov/hiv/group/age/index.html. Last Updated April 15, 2015. Accessed April 14, 2017.