Low-level viremia and risk of subsequent VL ≥ 1000 copies/mL among people living with HIV in Hunan Province, China: a large retrospective cohort study

The association between low-level viremia (LLV) and subsequent VL ≥ 1000 copies/mL among people living with HIV (PLWH) remains incompletely characterized in China. We examined the graded association between LLV levels and patterns and subsequent VL ≥ 1,000 copies/mL in a large cohort from Hunan Province. This retrospective cohort study included PLWH who initiated antiretroviral therapy (ART) between 2016 and 2024 and had at least one VL measurement after 6 months of treatment. LLV (50 to < 1,000 copies/mL) was characterized by level (LLLV: 50–199; MLLV: 200–399; HLLV: 400–999) and pattern (intermittent vs. persistent). Time-varying Cox regression was used to estimate associations with subsequent VL ≥ 1,000 copies/mL. Among 38,008 participants (median follow-up: 38.81 months; IQR: 13.99–64.94), 23.50% of participants experienced at least one LLV episode. The overall incidence rates of LLV and VL ≥ 1000 copies/mL were 8.12 (95% CI: 7.95–8.29) and 2.04 (95% CI: 1.97–2.12) per 100 person-years, respectively. A graded association was observed: adjusted HRs for LLLV, MLLV, and HLLV were 1.91 (95% CI: 1.59–2.30), 3.84 (95% CI: 2.90–5.08), and 6.46 (95% CI: 5.25–7.94), respectively (all P < 0.001). Intermittent LLV (aHR = 2.87, 95% CI: 2.50–3.31) and persistent LLV (aHR = 2.82, 95% CI: 1.89–4.22) were both associated with the outcome. In a direct comparison, pLLV was not associated with a significantly higher hazard than iLLV (aHR = 0.98, 95% CI: 0.68–1.42). Male sex, higher baseline VL, longer diagnosis-to-ART interval cross-regional medical visitis and Post-2023 ART initiation were associated with increased risk; older age and homosexual transmission were associated with lower risk. Baseline CD4 count and education level were included as stratification variables in the primary model. Sensitivity analyses, including restriction to participants with available baseline VL, follow-up truncation, and inverse-intensity weighting, yielded consistent estimates. LLV level and pattern were associated with subsequent VL ≥ 1,000 copies/mL, with a graded association across LLV levels. Patients with LLV, especially those with higher LLV levels, may require closer monitoring and early intervention to reduce the risk of subsequent VL ≥ 1000 copies/mL.