Initial antiretroviral therapy regimen and risk of heart failure

Abstract

Objective(s): Heart failure (HF) risk is elevated in people with HIV (PWH). We investigated whether initial antiretroviral therapy (ART) regimens influenced HF risk. Design: Cohort study Methods: PWH who initiated an ART regimen between 2000–2016 were identified from three integrated healthcare systems. We evaluated HF risk by protease inhibitor (PI), non-nucleoside 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 PI vs. NNRTI; 5 years for tenofovir vs. abacavir; 2 years for INSTIs vs. PIs or NNRTIs). Hazard ratios (HRs) were from working logistic marginal structural models, fitted with inverse probability weighting to adjust for demographics, and traditional cardiovascular risk factors. Results: 13,634 PWH were included (88% men, median 40 years of age; 34% non-Hispanic white, 24% non-Hispanic black, and 24% Hispanic). The HR (95% CI) were: 2.5 (1.5–4.3) for PI vs. NNRTI-based ART (reference); 0.5 (0.2–1.8) for PI 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 non-proportional hazards over time, the only remaining finding was evidence of a higher risk of HF for PI compared with NNRTI-based regimens (1.8% vs. 0.8%; P = 0.002). Conclusions: PWH initiating PIs may be at higher risk of HF compared with those initiating NNRTIs. Future studies with longer follow-up with INSTI-based and other specific ART are warranted.