Impact of HIV-1 low-level viremia on virologic and immunologic failure during antiretroviral therapy: a retrospective cohort study from 2005 to 2023 in Qinzhou City, Guangxi, China

BACKGROUND: Despite effective antiretroviral therapy (ART), a subset of people living with HIV(PLWH)experiences low-level viremia(LLV), yet its impact on subsequent virologic failure (VF) and immunologic failure (IF) remains unclear. This study aims to elucidate the effect of LLV on the risk of VF and IF. METHODS: This retrospective cohort study included PLWH aged ≥ 18 years who initiated ART in Qinzhou City, Guangxi, China, from 2005 to 2023. Participants were categorized into mutually exclusive viral load categories: undetectable viral load (≤ 50 copies/mL) and LLV (51-999 copies/mL). Time-updated Cox proportional hazards models were used to evaluate the association between LLV and the risk of VF and IF. RESULTS: A total of 4,274 participants were followed for 12,288.35 person-years, with a median follow-up of 3.03 years. Among these participants, 11.16% experienced at least one LLV event. Compared to those with an undetectable viral load, individuals with LLV had a significantly higher risk of VF (adjusted hazard ratio [aHR] = 5.23, 95% CI: 3.48-7.85), with intermittent low-level viremia (ILLV) showing the strongest association (aHR = 7.34, 95% CI: 4.92-10.94). Conversely, LLV was associated with a lower risk of IF compared with an undetectable viral load (aHR = 0.59, 95% CI: 0.37-0.92), a finding consistent with the reduced risk observed in the ILLV subgroup (aHR = 0.56, 95% CI: 0.33-0.96). CONCLUSIONS: Patients with LLV had an increased risk of subsequent VF, emphasizing the need for close monitoring of viral load and potential treatment adjustments to optimize long-term ART outcomes.