Coronary Microcirculatory Dysfunction in People With HIV and Its Association With Antiretroviral Therapy

J Am Heart Assoc. 2023 Nov 21;12(22):e029541. doi: 10.1161/JAHA.123.029541. Epub 2023 Nov 10.

Abstract

Background: HIV infection and abacavir-containing antiretroviral regimens are associated with vascular endothelial dysfunction and increased cardiovascular risk. Positron emission tomography (PET)-derived myocardial blood flow reserve (MBFR), the ratio of vasodilator stress to rest myocardial blood flow, is a well-validated measure of coronary microvascular health and marker of cardiovascular risk. Our objective was to compare MBFR among people with HIV (PWH) with matched non-HIV controls and to assess whether switching from dolutegravir/lamivudine/abacavir to the non-abacavir regimen bictegravir/emtricitabine/tenofovir alafenamide (TAF) would improve MBFR.

Methods and results: Thirty-seven PWH were 1:2 matched on cardiovascular risk factors to 75 people without HIV, and MBFR corrected for differences in resting hemodynamics was compared in a cross-sectional design. PWH were majority men (68%) with a mean age of 56 years. Mean stress myocardial blood flow (1.83 mL/min per g [95% CI, 1.68-1.98] versus 2.40 mL/min per g [95% CI, 2.25-2.54]; P<0.001) and MBFR (2.18 [95% CI, 1.96-2.40] versus 2.68 [95% CI, 2.47-2.89]; P=0.002) was significantly lower in PWH than in people without HIV. In a single-arm, multicenter trial, a subset of 25 PWH who were virologically suppressed on dolutegravir/lamivudine/abacavir underwent positron emission tomography myocardial perfusion imaging at baseline and after switching to bictegravir/emtricitabine/TAF. MBFR was unchanged after switching to bictegravir/emtricitabine/TAF for a mean of 27 weeks (MBFR, 2.34 to 2.29; P=0.61), except in PWH with impaired MBFR at baseline (<2.00; N=6) in whom MBFR increased from 1.58 to 2.02 (P=0.02).

Conclusions: PWH had reduced coronary microvascular function compared with controls without HIV. Coronary microvascular function did not improve after switching from dolutegravir/lamivudine/abacavir to bictegravir/emtricitabine/TAF.

Registration: URL: https://www.clinicaltrials.gov; unique identifier: NCT03656783.

Keywords: HIV; antiretroviral therapy; coronary microvascular dysfunction; heart; myocardial perfusion imaging.

Publication types

  • Clinical Trial, Phase III

MeSH terms

  • Adult
  • Aged
  • Alanine / therapeutic use
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use
  • Case-Control Studies
  • Coronary Circulation / drug effects
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / drug effects
  • Coronary Vessels / physiopathology
  • Cross-Sectional Studies
  • Dideoxynucleosides / therapeutic use
  • Drug Combinations
  • Drug Substitution
  • Emtricitabine / therapeutic use
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / physiopathology
  • Heterocyclic Compounds, 3-Ring / adverse effects
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Lamivudine / therapeutic use
  • Male
  • Microcirculation* / drug effects
  • Middle Aged
  • Myocardial Perfusion Imaging / methods
  • Oxazines / therapeutic use
  • Piperazines / therapeutic use
  • Positron-Emission Tomography
  • Pyridones / therapeutic use
  • Tenofovir / therapeutic use

Substances

  • abacavir, lamivudine drug combination
  • Alanine
  • Anti-HIV Agents
  • Dideoxynucleosides
  • dolutegravir
  • Drug Combinations
  • Emtricitabine
  • Heterocyclic Compounds, 3-Ring
  • Lamivudine
  • Oxazines
  • Piperazines
  • Pyridones
  • Tenofovir

Associated data

  • ClinicalTrials.gov/NCT03656783