BACKGROUND:The clinical management of low-level viremia (LLV) remains unclear. The objective of this study was to investigate the association of blips and LLV with virologic failure. METHODS:We enlisted patients who newly enrolled into the HIV Research Network between 2005 and 2015, had HIV-1 RNA more than 200 copies/ml, and were either antiretroviral therapy (ART)-naive or ART-experienced and not on ART. Patients were included who achieved virologic suppression (≤50 on two consecutive viral loads) and had at least two viral loads following suppression. Blips and LLV (≥2 consecutive >51 copies/ml) were categorized separately into three categoriesno blips/LLV, 51–200, 201–500. Cox proportional hazards regression was used to assess association between rates of blips/LLV and virologic failure (two consecutive >500). RESULTS:The 2795 patients were mostly male (75.4%), black (50.3%), and MSM (52.9%). Median age was 38 years old (interquartile range 29–48). Most patients (88.8%) were ART-naive at study entry. Overall, 283 (10.1%) patients experienced virologic failure. A total of 152 (5.4%) patients experienced LLV to 51–200 and 110 (3.9%) patients experienced LLV to 201–500. Both LLV 51–200 adjusted hazard ratio (aHR) 1.83 (1.10,3.04) and LLV 201–500 aHR 4.26 (2.65,6.86) were associated with virologic failure. In sensitivity analysis excluding ART-experienced patients, the association between LLV 51 and 200 and virologic failure was not statistically significant. CONCLUSION:LLV between 201 and 500 was associated with virologic failure, as was LLV between 51 and 200, particularly among ART-experienced patients. Patients with LLV below the current Department of Health and Human Services threshold for virologic failure (persistent viremia ≥200) may require more intensive monitoring because of increased risk for virologic failure.