The time at which antiretroviral therapy (ART) should be initiated in children with perinatal human immunodeficiency virus (HIV) infection remains controversial. In a cohort study, Berk et al1 reported clinical benefit from mono/dual ART started before 60 days of life in 10 children compared with treatment administered at 61 to 120 days of life in 16 children. The 23 children who received early triple ART were not investigated because none of them progressed to category C diagnosis by 3 years of age. We performed a similar analysis in a cohort study of a larger data set of children with a longer follow-up to evaluate the outcomes of early and very early triple ART. Methods This was a post hoc analysis of data collected by the Italian Register for HIV Infection in Children, a network of 106 pediatric clinics distributed throughout Italy that is highly representative of the Italian population of perinatally HIV-infected children; details are described elsewhere.2 Approval for the study was granted from the University of Florence and the ethics committees of the participating institutions, and written informed consent was obtained from children's parents or legal guardians. Children infected with HIV born in 1988-2001 who received early ART treatment (≤120 days of life) with at least 3 years of follow-up or earlier death were included. Treatments were considered if they were given continuously for at least 1 month in children who remained free of category C diagnoses for 1 month after initiating therapy.1 Children who progressed to triple ART after starting mono/dual ART were excluded from the analysis because of potential modification of the effect of the triple therapy. The following comparisons were performed using Kaplan-Meier analysis with the log-rank test: (1) mono/dual ART vs triple ART at age 120 days or younger; (2) very early (≤60 days) vs early (61-120 days) mono/dual ART; and (3) very early vs early triple ART. Cox regression analysis was performed to evaluate the risk of progression to category C diagnosis adjusted for the year of study entry (before 1996 vs 1996 or later) and baseline CD4+ T-cell percentage. The sample size had a power of 80% to detect a 50% difference between triple vs mono/dual ART and between very early vs early ART, with a 2-sided α = .05 and an assumption that 69% of children receiving only mono/dual therapy and no subsequent triple ART would progress to category C diagnosis.1 Statistical analyses were performed using SPSS software, version 11.5 (SPSS Inc, Chicago, Ill). P<.05 was considered statistically significant. Results Forty-one children received mono/dual ART and 22 children received triple ART (Table). The proportion progressing to category C diagnosis was significantly higher in children receiving mono/dual ART than in children receiving triple ART (28/41 [69.3%; 95% confidence interval {CI}, 61.9%-75.5%] vs 1/22 [4.5%; 95% CI, 0.2%-8.9%]; P<.001) (Figure). Death occurred in 18 of 41 (43.9%; 95% CI, 36.7%-51.6%) vs 0 of 22 children (P<.001), respectively, at a median (interquartile range) age of 20 (10-27) months. After adjusting for year of study entry and baseline CD4+ T-cell percentage, the risk of progression to category C diagnosis remained significantly greater for children receiving mono/dual ART (hazard ratio, 2.34; 95% CI, 1.16-23.14; P = .04).

Early triple therapy vs mono or dual therapy for children with perinatal HIV infection / Chiappini, Elena; Galli, Luisa; Gabiano, Clara; Tovo, Pier-Angelo; De Martino, Maurizio. - In: JAMA. - ISSN 0098-7484. - STAMPA. - 295:(2006), pp. 626-628. [10.1001/jama.295.6.626-b]

Early triple therapy vs mono or dual therapy for children with perinatal HIV infection.

CHIAPPINI, ELENA;GALLI, LUISA;DE MARTINO, MAURIZIO
2006

Abstract

The time at which antiretroviral therapy (ART) should be initiated in children with perinatal human immunodeficiency virus (HIV) infection remains controversial. In a cohort study, Berk et al1 reported clinical benefit from mono/dual ART started before 60 days of life in 10 children compared with treatment administered at 61 to 120 days of life in 16 children. The 23 children who received early triple ART were not investigated because none of them progressed to category C diagnosis by 3 years of age. We performed a similar analysis in a cohort study of a larger data set of children with a longer follow-up to evaluate the outcomes of early and very early triple ART. Methods This was a post hoc analysis of data collected by the Italian Register for HIV Infection in Children, a network of 106 pediatric clinics distributed throughout Italy that is highly representative of the Italian population of perinatally HIV-infected children; details are described elsewhere.2 Approval for the study was granted from the University of Florence and the ethics committees of the participating institutions, and written informed consent was obtained from children's parents or legal guardians. Children infected with HIV born in 1988-2001 who received early ART treatment (≤120 days of life) with at least 3 years of follow-up or earlier death were included. Treatments were considered if they were given continuously for at least 1 month in children who remained free of category C diagnoses for 1 month after initiating therapy.1 Children who progressed to triple ART after starting mono/dual ART were excluded from the analysis because of potential modification of the effect of the triple therapy. The following comparisons were performed using Kaplan-Meier analysis with the log-rank test: (1) mono/dual ART vs triple ART at age 120 days or younger; (2) very early (≤60 days) vs early (61-120 days) mono/dual ART; and (3) very early vs early triple ART. Cox regression analysis was performed to evaluate the risk of progression to category C diagnosis adjusted for the year of study entry (before 1996 vs 1996 or later) and baseline CD4+ T-cell percentage. The sample size had a power of 80% to detect a 50% difference between triple vs mono/dual ART and between very early vs early ART, with a 2-sided α = .05 and an assumption that 69% of children receiving only mono/dual therapy and no subsequent triple ART would progress to category C diagnosis.1 Statistical analyses were performed using SPSS software, version 11.5 (SPSS Inc, Chicago, Ill). P<.05 was considered statistically significant. Results Forty-one children received mono/dual ART and 22 children received triple ART (Table). The proportion progressing to category C diagnosis was significantly higher in children receiving mono/dual ART than in children receiving triple ART (28/41 [69.3%; 95% confidence interval {CI}, 61.9%-75.5%] vs 1/22 [4.5%; 95% CI, 0.2%-8.9%]; P<.001) (Figure). Death occurred in 18 of 41 (43.9%; 95% CI, 36.7%-51.6%) vs 0 of 22 children (P<.001), respectively, at a median (interquartile range) age of 20 (10-27) months. After adjusting for year of study entry and baseline CD4+ T-cell percentage, the risk of progression to category C diagnosis remained significantly greater for children receiving mono/dual ART (hazard ratio, 2.34; 95% CI, 1.16-23.14; P = .04).
2006
295
626
628
Chiappini, Elena; Galli, Luisa; Gabiano, Clara; Tovo, Pier-Angelo; De Martino, Maurizio
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/781986
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