Un traitement ARV précoce chez les enfants atteints du SIDA pour améliorer le statut immunologique et clinique à long terme - LANCET 22/08/2013

Sida : l'intérêt d'un traitement précoce se confirme

 Résumé en Français :

Selon une étude conduite par des chercheurs sud-africains et publiée jeudi dans le Lancet, un traitement temporaire précoce des enfants infectés par le virus du sida permet de retarder à la fois l'instauration d'un traitement à vie et la progression de la maladie. En 2007, les résultats préliminaires de ces travaux débutés en 2005 avaient déjà montré que le traitement précoce réduisait le risque de décès et de progression de la maladie de 75% par comparaison au traitement retardé, rappelle Le Parisien. Les résultats définitifs montrent qu'un traitement précoce d'une durée de 40 semaines a permis de retarder en moyenne l'instauration du traitement à vie de 33 semaines, contre 70 semaines pour le traitement précoce d'une durée de 96 semaines. Chez les enfants non immédiatement traités, le traitement à vie a dû être instauré au bout de 20 semaines. De plus, une partie non négligeable des enfants ayant reçu le traitement précoce n'avaient toujours pas repris de traitement à l'issue de l'étude de 5 ans (19% de ceux ayant reçu le traitement court et 32% de ceux ayant eu le traitement long). Le Dr Violari, co-auteur de l'étude, reconnaît toutefois que les chercheurs ne savent pas si un traitement précoce d'une durée encore plus longue ou non interrompue "n'aurait pas été encore meilleur". Selon des estimations de l'OMS, quelque 3,4 millions d'enfants de moins de 15 ans vivaient avec le VIH à la fin 2011, dont 91% en Afrique subsaharienne.

The Lancet, Early Online Publication, 22 August 2013

doi:10.1016/S0140-6736(13)61409-9Cite or Link Using DOI

This article can be found in the following collections: Infectious Diseases (HIV/AIDS, Paediatric infections); Paediatrics (Paediatric infections)

Copyright © 2013 Elsevier Ltd All rights reserved.

Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial

Prof Mark F Cotton MMed a *, Avy Violari FCPaed [SA] b *, Kennedy Otwombe MSc b, Ravindre Panchia MB b, Els Dobbels FCPaed [SA] a, Helena Rabie FCPaed [SA] a, Deirdre Josipovic MB b, Afaaf Liberty MB b, Erica Lazarus MB b, Steve Innes MB a, Anita Janse van Rensburg Dip Nurs a, Wilma Pelser RN b, Handre Truter NDip b, Prof Shabir A Madhi FCPaed c, Edward Handelsman MD d e, Patrick Jean-Philippe MD f, Prof James A McIntyre FRCOG g †, Prof Diana M Gibb MD h †, Prof Abdel G Babiker PhD h †, on behalf of the CHER Study Team

"Summary"

Background

Interim results from the children with HIV early antiretroviral (CHER) trial showed that early antiretroviral therapy (ART) was life-saving for infants infected with HIV. In view of the few treatment options and the potential toxicity associated with lifelong ART, in the CHER trial we compared early time-limited ART with deferred ART.

Methods

CHER was an open-label randomised controlled trial of HIV-infected asymptomatic infants younger than 12 weeks in two South African trial sites with a percentage of CD4-positive T lymphocytes (CD4%) of 25% or higher. 377 infants were randomly allocated to one of three groups: deferred ART (ART-Def), immediate ART for 40 weeks (ART-40W), or immediate ART for 96 weeks (ART-96W), with subsequent treatment interruption. The randomisation schedule was stratified by clinical site with permuted blocks of random sizes to balance the numbers of infants allocated to each group. Criteria for ART initiation in the ART-Def group and re-initiation after interruption in the other groups were CD4% less than 25% in infancy; otherwise, the criteria were CD4% less than 20% or Centers for Disease Control and Prevention severe stage B or stage C disease. Combination therapy of lopinavir—ritonavir, zidovudine, and lamivudine was the first-line treatment regimen at ART initiation and re-initiation. The primary endpoint was time to failure of first-line ART (immunological, clinical, or virological) or death. Comparisons were done by intention-to-treat analysis, with use of time-to-event methods. This trial is registered with ClinicalTrials.gov, number NCT00102960.

Findings

377 infants were enrolled, with a median age of 7·4 weeks, CD4% of 35%, and HIV RNA log 5·7 copies per mL. Median follow-up was 4·8 years; 34 infants (9%) were lost to follow-up. Median time to ART initiation in the ART-Def group was 20 weeks (IQR 16—25). Time to restarting of ART after interruption was 33 weeks (26—45) in ART-40W and 70 weeks (35—109) in ART-96W; at the end of the trial, 19% of patients in ART-40W and 32% of patients in ART-96W remained off ART. Proportions of follow-up time spent on ART were 81% in the ART-Def group, 70% in the ART-40W group, and 69% in the ART-96W group. 48 (38%) of 125 children in the ART-Def group, 32 (25%) of 126 in the ART-40W group, and 26 (21%) of 126 in the ART-96W group reached the primary endpoint. The hazard ratio, relative to ART-Def, was 0·59 (95% CI 0·38—0·93, p=0·02) for ART-40W and 0·47 (0·27—0·76, p=0·002) for ART-96W. Three children in ART-Def, three in ART-40W, and one in ART-96W switched to second-line ART.

Interpretation

Early time-limited ART had better clinical and immunological outcomes than deferred ART, with no evidence of excess disease progression during subsequent treatment interruption and less overall ART exposure than deferred ART. Longer time on primary ART permits longer subsequent interruption, with marginally better outcomes.

Funding

US National Institutes of Health.