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)61409-9
Cite or Link Using DOI
Cite 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
Mark F Cottona*
Avy ViolaribKennedy OtwombebRavindre PanchiabEls DobbelsaHelena RabieaDeirdre JosipovicbAfaaf LibertybErica LazarusbSteve InnesaAnita Janse van RensburgWilma PelserbHandre TruterShabir A MadhiEdward HandelsmanPatrick Jean-PhilippeJames A McIntyre†Diana M Gibbh†Abdel G Babiker, on behalf of the CHER Study Team
Avy ViolaribKennedy OtwombebRavindre PanchiabEls DobbelsaHelena RabieaDeirdre JosipovicbAfaaf LibertybErica LazarusbSteve InnesaAnita Janse van RensburgWilma PelserbHandre TruterShabir A MadhiEdward HandelsmanPatrick Jean-PhilippeJames A McIntyre†Diana M Gibbh†Abdel G Babiker, 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.
