Early antiretroviral therapy in HIV-1-infected infants, 1996–2008: treatment response and duration of first-line regimens


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Abstract

Objective:To investigate virological and immunological response to antiretroviral therapy (ART), and predictors of switching and interrupting treatment among infants starting ART across Europe.Design:Cohort study.Methods: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.Results: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.Conclusion: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.

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