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Objectives: We investigated the association between persistent low-level viraemia, measured as viraemia copy-years (VCY), and all-cause mortality.Methods: We included 3271 HIV-infected patients who initiated their first combined ART (cART) during 1998-2012 enrolled in the multicentre Italian MASTER cohort. VCY was defined as the area under the curve of plasma viral load (pVL) and expressed in log10 copies · years/mL. VCY was evaluated from cART initiation until the end of follow-up [VCY-overall (VCY-o)], and stratified into before [VCY-early (VCY-e)] and after [VCY-late (VCY-l)] the eighth month from starting cART, and as the ratio of VCY-l to follow-up duration (VCY-l/FUD).Results: The risk of death increased of about 40% for higher than the median levels of VCY-o and VCY-e. Compared with subjects with permanently suppressed pVL after the eighth month from starting cART, mortality increased by 70% for those with VCY-l ≥3 log10 copies·years/mL, and by about 20-fold for those with VCY-l/FUD ≥2.3 log10 copies/mL. Patients who maintained low levels of VCY-l (<3 log10 copies · years/mL) or VCY-l/FUD (<2.3 log10 copies/mL) had a risk of death similar to patients with permanently suppressed pVL. CD4 cell count at baseline was predictive of high risk of death only in subjects with VCY-l ≥3 log10 copies · years/mL.Conclusions: The risk of death did not increase in HIV-infected patients with low levels of VCY-l compared with patients with permanent virological suppression. [ABSTRACT FROM AUTHOR]