Sustained viral suppression (VL < 50 copies/mL) is the main target of ART, essential for immune restoration, prevention of transmission, and normalization of survival among people living with HIV (PLWH). However, some individuals maintain detectable VL between 50–199 copies/mL, characterizing persistent low-level viremia (LLV). Although LLV does not constitute classic virologic failure, it has been associated with systemic inflammation, cardiovascular risk, and emergence of resistance mutations. This study estimated the prevalence of LLV and early therapeutic failure (ETF), as well as possible associations with ART regimens, in a real-life cohort from a national reference center.

Longitudinal analysis of a cohort of 1,050 PLWH with ≥ 4 semiannual VL measurements between the first semester of 2023 and the second semester of 2024, with recorded ART regimen. LLV was defined as ≥ 2 consecutive VLs between 50–199 copies/mL; ETF as VL between 200–499 copies/mL. Prevalences and 95% confidence intervals (95% CI) were estimated using the Wilson method.

Among the 1,050 individuals, 57 (5.43%) had persistent residual viremia. Of these, 25 met criteria for LLV (2.38%; 95% CI: 1.62–3.49) and 32 for ETF (3.05%; 95% CI: 2.17–4.27). The LLV:ETF ratio was 4:5. Among those with detectable VL, 43.9% had LLV and 56.1% ETF, suggesting a risk of early progression to sustained virologic failure. No statistically significant association was identified between occurrence of LLV/ETF and type of ART regimen, regardless of whether regimens were simplified two-drug (2D) regimens, traditional three-drug (3D) regimens, or regimens based on integrase inhibitors (INSTI) or protease inhibitors (PI).

The prevalence of LLV in this cohort (2.38%) was lower than that reported in large international cohorts: 3.5% in a US–Europe consortium and 9.9% in a European study defining LLV as two consecutive VLs between 51–199 copies/mL after 12 months of ART. These data reinforce the effectiveness of current regimens; however, residual viremia, even at low levels, requires close monitoring. Continuous surveillance – emphasizing adherence, pharmacokinetics, and therapeutic adjustments – is an essential component of management. Detectable VL in two consecutive semesters, even at low levels, may represent a critical window for intervention, especially in contexts of irregular adherence or inflammatory comorbidities.