Abstract
BACKGROUND: Low-level viremia (LLV) during effective antiretroviral therapy (ART) presents ongoing management challenges globally, with reported prevalence rates of 10-46% in resource-limited settings. The clinical significance of LLV remains controversial: while some studies demonstrate that viral load (VL) levels exceeding 200 copies/mL predict virologic failure (VF), others report no significant association. This uncertainty underscores the need for clearer risk stratification in diverse clinical settings. OBJECTIVE: To investigate risk factors for VF and persistent low-level viremia (pLLV) in HIV-1-infected individuals experiencing LLV. DESIGN: A retrospective cohort study between January 2019 and December 2023, consisting of 1,214 individuals with LLV (defined as plasma HIV-1 RNA levels of 50-999 copies/mL detected at two consecutive time points following previously undetected viral loads) at a large specialized hospital in Chongqing, China. METHODS: Clinical data, including demographics, ART regimens, adherence, baseline viral load (VL), CD4 + T-cell counts, and LLV characteristics, were extracted from medical records. Univariate and multivariate logistic regression models were used to identify factors associated with VF (defined as one or more HIV VLs of ≥1,000 copies/mL) and pLLV (defined as at least three consecutive measurements of VL within the range of 50 to 999 copies/mL), with adjustments for potential confounders. RESULTS: Among 1,214 participants with LLV, 2.64% (32/1,214) developed VF, and 28.09% (341/1,214) developed pLLV. Protective factors against VF included baseline VL < 1,000 copies/mL (adjusted odds ratio [aOR] = 0.100, 95%CI: 0.013-0.765) and VL < 200 copies/mL during LLV (aOR = 0.157, 95%CI: 0.071-0.540). Viral blips (transient LLV) independently predicted VF (aOR = 4.6775, 95%CI: 1.392-15.704). For pLLV, baseline VL < 1,000 copies/mL remained protective (aOR = 0.569, 95% CI: 0.329-0.984), while primary education or lower was a risk factor (aOR = 2.052, 95%CI: 1.014-4.194). CONCLUSION: VL levels during LLV and baseline VL predict VF risk, emphasizing the need for vigilant VL monitoring and adherence support.