Residual HIV viremia strongly increases cardiovascular disease incidence independent of classical risk factors

Abstract

SummaryBackgroundPeople with HIV (PWH) using antiretroviral therapy are at increased risk to develop cardiovascular diseases (CVD). We hypothesized that residual viremia (RV; unquantifiable low, but detectable viral load) increases CVD risk.MethodsWe enrolled 1895 virally suppressed PWH and compared CVD incidence in participants with and without RV. Extensive multi-omics characterization was performed. Incident CVD was registered after 2-year follow-up and adjusted odds ratios (aOR) calculated accounting for classical CVD risk factors. The numbers of expected and actual CVD events were compared using CVD risk scores.FindingsRV, detected in one-third of participants, strongly increased the risk of developing a first cardiovascular event (3.1% vs 1.2%, aOR 2.8, p=0.004). Participants with RV experienced twice the number of events predicted by the SCORE2 risk model. The association between RV and CVD was not driven by inflammation, immune activation, gut barrier dysfunction, or lipometabolic perturbations.InterpretationResidual viremia independently associated with CVD development, highlighting the need for tailored prevention and examination of novel intervention strategies.