Initial antiretroviral therapy regimen and risk of heart failure

AIDS. 2024 Mar 15;38(4):547-556. doi: 10.1097/QAD.0000000000003786. Epub 2023 Nov 14.

Abstract

Objectives: Heart failure risk is elevated in people with HIV (PWH). We investigated whether initial antiretroviral therapy (ART) regimens influenced heart failure risk.

Design: Cohort study.

Methods: PWH who initiated an ART regimen between 2000 and 2016 were identified from three integrated healthcare systems. We evaluated heart failure risk by protease inhibitor, nonnucleoside reverse transcriptase inhibitors (NNRTI), and integrase strand transfer inhibitor (INSTI)-based ART, and comparing two common nucleotide reverse transcriptase inhibitors: tenofovir disoproxil fumarate (tenofovir) and abacavir. Follow-up for each pairwise comparison varied (i.e. 7 years for protease inhibitor vs. NNRTI; 5 years for tenofovir vs. abacavir; 2 years for INSTIs vs. PIs or NNRTIs). Hazard ratios were from working logistic marginal structural models, fitted with inverse probability weighting to adjust for demographics, and traditional cardiovascular risk factors.

Results: Thirteen thousand six hundred and thirty-four PWH were included (88% men, median 40 years of age; 34% non-Hispanic white, 24% non-Hispanic black, and 24% Hispanic). The hazard ratio (95% CI) were: 2.5 (1.5-4.3) for protease inhibitor vs. NNRTI-based ART (reference); 0.5 (0.2-1.8) for protease inhibitor vs. INSTI-based ART (reference); 0.1 (0.1-0.8) for NNRTI vs. INSTI-based ART (reference); and 1.7 (0.5-5.7) for tenofovir vs. abacavir (reference). In more complex models of cumulative incidence that accounted for possible nonproportional hazards over time, the only remaining finding was evidence of a higher risk of heart failure for protease inhibitor compared with NNRTI-based regimens (1.8 vs. 0.8%; P = 0.002).

Conclusion: PWH initiating protease inhibitors may be at higher risk of heart failure compared with those initiating NNRTIs. Future studies with longer follow-up with INSTI-based and other specific ART are warranted.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-HIV Agents* / adverse effects
  • Cohort Studies
  • Cyclopropanes*
  • Dideoxyadenosine / analogs & derivatives*
  • Dideoxynucleosides / adverse effects
  • Female
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • HIV Protease Inhibitors* / adverse effects
  • Heart Failure* / chemically induced
  • Heart Failure* / drug therapy
  • Heart Failure* / epidemiology
  • Humans
  • Male
  • Reverse Transcriptase Inhibitors / adverse effects
  • Tenofovir / adverse effects

Substances

  • Reverse Transcriptase Inhibitors
  • abacavir
  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Dideoxynucleosides
  • Tenofovir
  • Cyclopropanes
  • Dideoxyadenosine