Low-level viremia linked to virological failure but not clinical events: a competing risks study

Introduction: The main objective of ART for people with HIV is to maintain an undetectable viral load. This study evaluates the association between low-level viremia (50–200 copies/mL) and virological failure, AIDS, and severe non-AIDS events, as well as the impact of sociodemographic and clinical factors. Materials and methods: Data were collected from the Spanish HIV/AIDS research network (CoRIS), comprising ART-naïve adults recruited from 47 centers across Spain. Eligible participants were those who achieved viral suppression (VL <200 copies/mL) within 3–9 months post-ART initiation and had follow-up data. Participants were classified into two groups: No-LLV (VL ≤50 copies/mL or a single measurement >51 but <1,000 copies/mL) and LLV1 (51–199 copies/mL in two consecutive measurements). The outcomes included VF, AIDS, and severe NAE. Statistical analyses involved Competing risk analysis and multinomial logistic regression. Results: Of 12,110 participants, 89.7% were No-LLV and 10.3% LLV1. LLV groups had higher median age and lower CD4+ counts. VF occurred in 12.3% of LLV1 compared to 4.68% in the No-LLV group (p < 0.001). In the competitive risk analysis, the Hazard Ratio for virological failure of LLV1 was 1.39 (97.5% CI 1.28–1.53) p < 0.0001, ART from 2016–2021 was 0.70 (97.5% CI 0.64–0.77), p < 0.001, ART with PI was 1.09 (97.5% CI 1.01–1.19), p < 0.001, HIV VL ≥ 100.000 copies/ml 1.17 (97.5% CI, 1.01–1.35; p = 0.036) and CD4 > 200 cells/ml was 0.73 (97.5% CI 0.61–0.87), p < 0.001. LLV1 were not associated with an increased risk of AIDS, mortality or NAE. Conclusions: Low-level viremia (50–200 copies/mL) was associated with an increased risk of virological failure. However, it was not linked to a higher likelihood of clinical events (AIDS-related, non-AIDS-related, or death). Therefore, while close monitoring is necessary due to the risk of virological failure, these findings provide reassurance as LLV does not translate into adverse clinical outcomes.