Virologic failure following low-level viremia and viral blips during antiretroviral therapy: results from a European multicenter cohort

It is unclear whether low-level viremia (LLV), defined as repeatedly detectable viral load (VL) of <200 copies/mL, and/or transient viremic episodes (blips) during antiretroviral therapy (ART), predict future virologic failure. We investigated the association between LLV, blips, and virologic failure (VF) in a multi-center European cohort.People with HIV-1 who started ART 2005 or later were identified from the EuResist Integrated Database. We analyzed the incidence of VF (≥200 copies/mL) depending on viremia exposure, starting 12 months after ART initiation (grouped as suppression [≤50 copies/mL], blips [isolated VL of 51–999 copies/mL], and LLV [repeated VLs of 51–199 copies/mL]) using Cox proportional hazard models adjusted for age, sex, injecting drug use, pre-ART VL, CD4 count, HIV-1 subtype, type of ART, and treatment experience. We queried the database for drug resistance mutations (DRM) related to episodes of LLV and VF and compared those with baseline resistance data.During 81,837 person-years of follow-up, we observed 1,424 events of VF in 22,523 participants. Both blips (adjusted subhazard ratio [aHR], 1.7; 95% confidence interval [CI], 1.3−2.2) and LLV (aHR, 2.2; 95% CI, 1.6−3.0) were associated with VF, compared with virologic suppression. These associations remained statistically significant in sub-analyses restricted to people with VL <200 copies/mL and those starting ART 2014 or later. Among people with LLV and genotype data available within 90 days following LLV, 49/140 (35%) had at least one DRM.Both blips and LLV during ART are associated with increased risk of subsequent VF.