Low-level viremia linked to virological failure but not clinical events

The main objective of antiretroviral therapy (ART) for people with HIV (PWH) is to maintain an undetectable viral load. This study evaluates the association between low-level viremia (LLV) (50-200 copies/ml) and virological failure, AIDS, and severe non-AIDS events, as well as the impact of sociodemographic and clinical factors.

Data were collected from the Spanish HIV/AIDS research network (CoRIS), comprising ART-naive adults recruited from 47 centers across Spain. Eligible participants were those who achieved viral suppression (viral load <200 copies/ml) within 3-9 months post-ART initiation and had follow-up data. Participants were classified into two groups: No-LLV (viral load ≤50 copcies/ml or a single measurement >51 but <1000 copies/ml) and LLV1 (51-199 copies/ml in two consecutive measurements). The outcomes included virological failure, AIDS, and severe non-AIDS events (NAE). Statistical analyses involved Competing risk analysis and multinomial logistic regression.

Of 12 110 participants, 89.7% were No-LLV and 10.3% LLV1. LLV groups had higher median age and lower CD4 + counts. Virological failure 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% confidence interval (CI) 1.28-1.53, P  < 0.0001], ART from 2016 to 2021 was 0.70 (97.5% CI 0.64-0.77, P  < 0.001), ART with protease inhibitor was 1.09 (97.5% CI 1.01-1.19, P  < 0.001), HIV viral load at least 100 000 copies/ml 1.17 (97.5% CI, 1.01-1.35; P  = 0.036) and CD4 + cell count greater than 200 cells/μl 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.

LLV (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.