TOPLINE:

Residual viraemia — an unquantifiable low, yet detectable HIV viral load — was associated with a more than twofold higher risk for incident cardiovascular disease (CVD) in people with HIV (PWH). This excess risk was independent of traditional CVD risk factors.

METHODOLOGY:

• Researchers conducted a prospective cohort study to assess whether residual viraemia was independently associated with incident CVD among virally suppressed PWH.
• They compared 610 adults with residual viraemia — defined as HIV RNA < 40 copies/mL — with 1192 adults with no detectable HIV RNA viral load; all adults were virally suppressed on antiretroviral therapy for at least 6 months.
• Baseline assessments included carotid plaque ultrasound, plasma proteomics, lipoprotein and metabolite quantification, and HIV proviral DNA quantification.
• The primary outcome was the occurrence of incident CVD — defined as stroke, transient ischaemic attack, myocardial infarction, angina pectoris, or peripheral artery disease — over a 2-year follow-up period; those with prior CVD were excluded from the analysis.
• Standard risk scores (SCORE2 and LIFE-CVD2) were used to predict the expected number of CVD events during follow-up.

TAKEAWAY:

• Residual viraemia was associated with a more than twofold higher risk for incident CVD than no detectable viral load (adjusted odds ratio, 2.8; P = .004) after adjusting for age, sex assigned at birth, smoking status, BMI, diabetes, hypertension, hypercholesterolaemia, and family history of CVD.
• Standard risk scores underpredicted CVD events in the residual viraemia group: Observed events were roughly twice the number predicted by SCORE2 (P = .024) and LIFE-CVD2 (P = .005); predictions were accurate in the no detectable viral load group.
• Residual viraemia was correlated with higher total HIV proviral DNA copies per million CD4 T cells (P = .038).
• Multiomics analysis showed no clear between-group differences in plasma lipoproteins, metabolites, inflammatory markers, immune activation, or gut barrier dysfunction markers, suggesting that systemic inflammation is unlikely to explain the residual viraemia-CVD association.

IN PRACTICE:

"Taken together, our analyses argue against a role for chronic inflammation, immune activation, gut barrier dysfunction, lipometabolic perturbations, or current ART [antiretroviral therapy] regimen as driver of CVD in RV [residual viraemia]. Instead our data suggest exposure to HIV viral products itself, may contribute to plaque stability," the authors wrote.

SOURCE:

This study was led by Twan Otten, Radboud University Medical Center, Nijmegen, Netherlands. It was published online on March 20, 2026, in the Journal of Infection.

LIMITATIONS:

The study was observational; therefore, causality could not be inferred. Adults were recruited from health centres in Western Europe, potentially limiting generalisability to other settings or populations. A small number of CVD cases and large between-person variability limited the power to detect smaller effects in omics analysis in specific groups.

DISCLOSURES:

This study was supported by an unrestricted grant from ViiV Healthcare. One author disclosed being a scientific founder of TTxD and Lemba.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.