Low-Level Viremia in People Living with HIV: A Retrospective Cohort Study

Background: Durable virological suppression is achieved in the majority of people living with HIV (PLWH) receiving contemporary antiretroviral therapy (ART). However, a subset of patients experience persistent low-level viremia (LLV), the clinical relevance and underlying determinants of which remain incompletely understood. Methods: Adult PLWH followed between 1 January 2005 and 31 December 2025 were retrospectively evaluated. LLV was defined as detectable HIV-1 RNA < 200 copies/mL on at least two consecutive measurements during follow-up in individuals receiving ART for at least 6 months. Patients with sustained virological suppression served as controls. Propensity score matching (1:1) was performed using variables associated with LLV in univariate analyses. Multivariable logistic regression analysis was applied to identify factors independently associated with LLV, and a p value < 0.05 was considered statistically significant. Results: Among 880 PLWH, 45 patients with LLV and 113 virologically suppressed controls were included. LLV was associated with lower baseline CD4+ T-cell counts, higher baseline HIV-1 RNA levels, delayed virological suppression at weeks 8 and 24, increased frequency of AIDS-defining illnesses and a higher prevalence of metabolic comorbidities, including hypertension, diabetes mellitus or dyslipidemia in univariate analysis. After propensity score matching, 32 patients remained in each group, with no clear association between low-level viremia and antiretroviral regimen class. Multivariable regression analysis showed baseline CD4+ T-cell count < 200 cells/µL, and the presence of ≥1 metabolic comorbidity (hypertension, diabetes mellitus or dyslipidemia) remained independently associated with LLV. Conclusions: Our findings suggest that LLV is associated with host-related factors rather than antiretroviral regimen failure. The coexistence of immunological impairment and metabolic comorbidities in patients with LLV underscores the importance of comprehensive clinical evaluation.