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To evaluate the relationship between incomplete antiretroviral therapy (ART) adherence and levels of residual HIV-1 viremia.Medication adherence and residual viremia less than 50 copies/ml were quantified in participants of a cohort of homeless and marginally housed individuals with HIV/AIDS.Participants had at least 6 months of virologic suppression of less than 50 copies/ml and were in the adherence monitoring cohort with monthly unannounced pill counts. Residual viremia was measured by the single-copy assay.The median average ART adherence over the prior 1 and 2 months were 94% [interquartile range (IQR) 79–100%] and 93% (IQR 82–98%), respectively. Average ART adherence over the past 2 months was significantly associated with levels of residual HIV viremia (Spearman r = –0.25, P = 0.04). One-third of participants with 100% ART adherence over the past 2 months had detectable residual viremia. On multivariate regression analysis, ART adherence over the past 2 months, but not duration of virologic suppression, CD4+ T-cell count or ART regimen, was significantly associated with levels of residual HIV viremia. Detectable residual viremia was associated with virologic failure (>50 copies/ml) on univariate Cox proportional hazard analysis (hazard ratio 2.08, P = 0.02). However, on multivariate analysis, only ART adherence was associated with risk of virologic failure.Incomplete ART adherence is associated with higher levels of residual HIV-1 viremia, but detectable residual viremia can be present despite 100% measured ART adherence.