Risk of virological failure in HIV-1-infected patients experiencing low-level viraemia under active antiretroviral therapy (ANRS C03 cohort study).

Background: We assessed the association of persistent low-level viraemia between 50-199 copies/ml (LLV) with the risk of virological failure (VF) among HIV-1-infected patients receiving combination antiretroviral therapy (ART). Methods: ART-naive and ART-experienced patients followed up in the ANRS-CO3 Aquitaine Cohort were included if they started two nucleoside reverse transcriptase inhibitors (NRTIs) with either one non-nucleoside reverse transcriptase inhibitor (NNRTI) or one protease inhibitor boosted with ritonavir (PI/r) between 2000 and 2011 and achieved viral load (VL)<200 copies/ml 4-8 months after initiating ART. VF was defined as either two consecutive VL >= 200 copies/ml or one VL >= 200 followed by a modification of ART. LLV was defined as at least two consecutive VLs between 50-199 copies/ml for at least one month. We used Cox models to estimate the association of LLV with VF. Results: Among 2,374 patients with a median follow-up of 3 years, 205 (8.6%) experienced LLV. LLV was strongly associated with further VF (adjusted hazard ratio [aHR] 2.30, 95% CI 1.65, 3.20). LLV was associated with VF in ART-experienced patients (aHR 3.02, 95% CI 2.10, 4.33) but not in ART-naive patients. Neither type of ART regimen (PI/r-versus NNRTI-based regimen) nor cumulative duration of LLV was associated with VF. Conclusions: Persistent LLV between 50-199 copies/ml was associated with VF among ART-experienced patients under ART. LLV between 50-199 copies/ml in ART-experienced patients should lead, after assessing patient's adherence and checking for drug interactions, to a closer monitoring and to consider ART optimization.