Low-Level Viremia as an Independent Risk Factor for Metabolic Syndrome in People Living with HIV Receiving Antiretroviral Therapy: A 6-Year Retrospective Cohort Study.

Purpose: Metabolic syndrome (MetS) in people living with HIV (PLWH) is more complicated and multifactorial than in the general population. HIV infection is increasingly recognized as a direct contributor to metabolic dysfunction. This study aims to assess the long-term risk of MetS in PLWH with low-level viremia (LLV) receiving antiretroviral therapy (ART). Patients and Methods: In this 6-year retrospective cohort study, we analysed 848 PLWH receiving ART. Participants were classified into three viremia categories: no LLV (all HIV viral loads <50 copies/mL or undetectable), LLV 51-200 (two consecutive viral loads between 51-200 copies/mL), and LLV 201-500 (two consecutive viral loads between 201-500 copies/mL). MetS incidence was assessed using time-dependent Cox regression analysis, while immune and metabolic trajectories were analyzed via linear mixed models. To further validate the robustness of our primary findings, sensitivity analyses stratified by ART regimens were performed. Results: Over a median follow-up of 3.9 years, 31.3% of participants developed MetS. The incidence rates of MetS were 160.4, 136.6, and 83.0 cases per 1000 person-years in the LLV 201-500, LLV 51-200, and no LLV groups, respectively. Time-dependent Cox regression analysis demonstrated that LLV was an independent risk factor for MetS. Sensitivity analyses demonstrated that patients experiencing LLV, irrespective of ART regimen, had a persistently higher incidence of MetS. Additionally, LLV was associated with persistently elevated CD8 counts, reduced CD4 recovery, and worsening metabolic profiles. Conclusion: LLV independently predicts MetS risk in PLWH on ART. LLV should be regarded not only as a virological concern but also as a metabolic risk factor that warrants closer clinical attention in the post-ART era.