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Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV: an international cohort collaboration
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International audience. Background—Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration.Methods—In this international cohort collaboration study, we pooled individual patient-leveldata for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART wasdefined as change of one or more NRTI plus either change in drug class (NNRTI to proteaseinhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor,or addition of a new drug class. We used cumulative incidence curves to assess time to switching,and multivariable proportional hazards models to explore patient-level and cohort-level factorsassociated with switching, with death and loss to follow-up as competing risks.Findings—At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in theCIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. AtART initiation, the median patient age was 3·9 years (IQR 1·6–6·9) and 82 885 (88·8%) patientsinitiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Medianduration of follow-up after ART initiation was 26 months (IQR 9–52). 3883 (4·2%) patientsswitched to second-line ART after a median of 35 months (IQR 20–57) of ART. The cumulativeincidence of switching at 3 years was 3·1% (95% CI 3·0–3·2), but this estimate varied widelydepending on the cohort monitoring strategy, from 6·8% (6·5–7·2) in settings with routinemonitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6–1·0) in settings with clinicalonly monitoring. In multivariable analyses, patient-level factors associated with an increasedlikelihood of switching were male sex, older age at ART initiation, and initial NNRTI-basedregimen (p<0·0001). Cohort-level factors that increased the likelihood of switching were higher-income country (p=0·0017) and routine or targeted monitoring of CD4 and viral load (p<0·0001),which was associated with a 166% increase in likelihood of switching compared with CD4 onlymonitoring (subdistributional hazard ratio 2·66, 95% CI 2·22–3·19).Interpretation—Our global paediatric analysis found wide variations in the incidence ofswitching to second-line ART across monitoring strategies. These findings suggest the scale-up ofviral load monitoring would probably increase demand for paediatric second-line ARTformulations
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