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Interruption of cART in Clinical Practice Is Associated With an Increase in the Long-Term Risk of Subsequent Immunosuppression in HIV-1-Infected Children

Aupiais, Camille MD*†; Faye, Albert MD, PhD†‡; Le Chenadec, Jerome MSc*; Rouzioux, Christine PharmD, PhD‡§; Bouallag, Naïma PhD*; Laurent, Corinne BS*; Blanche, Stephane MD§¶; Dollfus, Catherine MD; Warszawski, Josiane MD, PhD*††**; for the ANRS EPF-CO10 French Pediatric Cohort

Pediatric Infectious Disease Journal:
doi: 10.1097/INF.0000000000000450
HIV Reports
Abstract

Background: Antiretroviral treatment interruption (TI) is not recommended in HIV-infected children. We aimed to evaluate the context and consequences of TI in clinical practice.

Methods: We investigated the probability and risk factors of a first TI in the 483 children treated with combined ART (cART) in the ANRS French national pediatric cohort. Immunologic and virologic outcomes were compared between patients with TI (TI group) and those on continuous treatment (matched control group), from a baseline defined as the age at first interruption for the TI child and the corresponding age for the control child.

Results: At least one TI ≥ 3 months occurred in 42.4% of patients, at a median age of 8.0 years, for a median duration of 12.1 months. After cART initiation, the risk of TI was 7.0% (5.0–9.6) at 1 year and 30.3% (26.1–35.0) at 5 years and was higher for children starting treatment before 2000 and for children starting cART before 6 months of age. AIDS-free survival was similar, but severe immunosuppression occurred earlier in the TI group than in the control group (adjusted HR = 3.1; 1.0–9.1; P = 0.04). Four years after baseline, the proportion of patients with CD4% ≥25% was lower in the TI group than in the control group (52.0% vs. 72.0%; P < 0.01), even among children restarting cART at least 6 months earlier (aRR = 0.5; 0.3–0.9; P = 0.03).

Conclusions: The risk of TI in clinical practice has decreased but remains high. In intent-to-treat analysis, TI was associated with a greater risk of subsequent immunosuppression, even after cART resumption.

Author Information

From the *Inserm, Centre for Research in Epidemiology and Population Health, U1018, Epidemiology of HIV and STI Team, Le Kremlin Bicêtre, France; AP-HP, Robert Debré Hospital, Paris, France; Univ Denis Diderot Paris 7, France; §AP-HP, Necker Hospital, Paris, France; Univ René Descartes, Paris 5, France; AP-HP, Trousseau Hospital, Paris, France; **Univ Paris-Sud, Le Kremlin-Bicetre, France; and ††AP-HP, Department of Public Health, Bicêtre Hospital, Le Kremlin-Bicêtre, France.

Accepted for publication May 14, 2014.

Meeting at which parts of the data were presented: 19th Conference on Retroviruses and Opportunistic Infections (CROI); Seattle, United States of America; March 6, 2012; Abstract # S-140.

For the work under consideration for publication, Josiane Warszawski received support for travel to meetings and grants for the French EPF-CO10 cohort from Agence Nationale de Recherche sur le Sida et les Hépatites Virales—Agence Autonome de l’INSERM (ANRS-INSERM). Unrelated to the submitted work, Christine Rouzioux has received a grant from the ANRS and patents for HIV, and Josiane Warszawski received grants for research and pharmacovigilance activities from the ANRS-INSERM, the Société Française de lutte contre les Cancers et leucémies de l’Enfant et de l’adolescent (SFCE), the Agence nationale de sécurité du médicament et des produits de santé (ANSM), and ViiV healthcare, Abbott, Parexel, and IATEC. The remaining authors have no conflicts of interest to declare.

This work was supported by the Agence Nationale de Recherche sur le Sida et les Hépatites Virales—Agence Autonome de l’INSERM (ANRS-INSERM).

Address for correspondence: Camille Aupiais, MD, Hôpital Robert Debré, Service d’Accueil des Urgences Pédiatriques. 48 boulevard Sérurier, 75935 Paris Cedex 19, France. E-mail: camille.aupiais@rdb.aphp.fr.

© 2014 by Lippincott Williams & Wilkins, Inc.