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To investigate virological and immunological response to antiretroviral therapy (ART), and predictors of switching and interrupting treatment among infants starting ART across Europe.Cohort study.Nine cohorts from 13 European countries contributed data on HIV-infected infants born 1996–2008 and starting ART before age 12 months. Logistic and linear regression, and competing risks methods were used to assess predictors of virological (viral load <400 copies/ml) and immunological (change in CD4 Z-score) response, switching to second-line ART and treatment interruptions with viral load less than 400 copies/ml.A total of 437 infants were followed for median 5.9 (interquartile range 2.3–7.6) years after starting ART; 30% had an AIDS diagnosis prior to ART initiation. 53% had suppressed viral load <400 copies/ml at 12 months in 1996–1999, increasing to 77% in 2004–2008. Virological and immunological responses at 12 months varied by initial ART type (P < 0.001 and P = 0.03, respectively), with four-drug nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens being superior [virological response <400 copies/ml adjusted odds ratio = 3.00, 95% confidence interval (CI) 1.24–7.23; mean increase in CD4 Z-score coefficient = 0.64, 95% CI 0.10–1.17] to both three-drug NNRTI-based (reference) and boosted protease inhibitor regimens which were similar. Rates of switching to second-line ART were lower among children starting four-drug NNRTI-based and boosted protease inhibitor-based regimens compared with three-drug NNRTI regimens (P = 0.03). Sixty five percent of infants remained on first-line ART without treatment interruption after 5 years.Effective and prolonged responses to first-line ART can now be achieved in infants starting early ART outside trial settings. Superior responses to four-drug NNRTI compared with boosted protease inhibitor or three-drug NNRTI regimens need further evaluation, as does treatment interruption following early ART.