title: HIV-1 virological remission lasting more than 12 years after interruption of early antiretroviral therapy in a perinatally infected teenager enrolled in the French ANRS EPF-CO10 paediatric cohort: a case report.
abstract: BACKGROUND
  Durable HIV-1 remission after interruption of combined antiretroviral therapy (ART) has been reported in some adults who started treatment during primary infection; however, whether long-term remission in vertically infected children is possible was unknown. We report a case of a young adult perinatally infected with HIV-1 with viral remission despite long-term treatment interruption.
  
  
  METHODS
  The patient was identified in the ANRS EPF-CO10 paediatric cohort among 100 children infected with HIV perinatally who started ART before 6 months of age. HIV RNA viral load and CD4 cell counts were monitored from birth. Ultrasensitive HIV RNA, peripheral blood mononuclear cell (PBMC)-associated HIV DNA, HIV-specific T-cell responses (ie, production of cytokines and capacity to suppress HIV infection), reactivation of the CD4 cell reservoir (measured by p24 ELISA and HIV RNA in supernatants upon phytohaemagglutinin activation of purified CD4 cells), and plasma concentrations of antiretroviral drugs were assessed after 10 years of documented control off therapy.
  
  
  RESULTS
  The infant was born in 1996 to a woman with uncontrolled HIV-1 viraemia and received zidovudine-based prophylaxis for 6 weeks. HIV RNA and DNA were not detected 3 days and 14 days after birth. HIV DNA was detected at 4 weeks of age. HIV RNA reached 2·17× 10(6) copies per mL at 3 months of age and ART was started. HIV RNA was undetectable 1 month later. ART was discontinued by the family at some point between 5·8 and 6·8 years of age. HIV RNA was undetectable at 6·8 years of age and ART was not resumed. HIV RNA has remained below 50 copies per mL and CD4 cell counts stable through to 18·6 years of age. After 11·5 years of control off treatment, HIV RNA was below 4 copies per mL and HIV DNA was 2·2 log10 copies per 10(6) PBMCs. The HLA genotype showed homozygosity at several loci (A*2301-, B*1503/4101, C*0210/0802, DRB1*1101-, and DQB1*0602-). HIV-specific CD8 T-cell responses and T-cell activation were weak.
  
  
  CONCLUSIONS
  Findings from this case suggest that long-term HIV-1 remission is possible in perinatally infected children who receive treatment early, with characteristics similar to those reported in adult HIV post-treatment controllers. Further studies are needed to understand the mechanisms associated with HIV remission and whether early treatment of infected children might favour the conditions needed to achieve HIV control after treatment discontinuation.
  
  
  BACKGROUND
  Agence de recherche ANRS (France Recherche Nord & Sud Sida-HIV Hépatites).
authors.affiliation: Laboratoire de Microbiologie Clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France; Unité d'Immunologie, Hématologie et Rhumatologie pédiatriques, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France; EA7327, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. Electronic address: pierre.frange@aphp.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Frange
authors.affiliation: Service de Pédiatrie Générale, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Faye
authors.affiliation: Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France; EA7327, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Avettand-Fenoël
authors.affiliation: Service d'Hématologie Pédiatrique, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France.
authors.forename: Erianna
authors.initials: E
authors.lastname: Bellaton
authors.affiliation: IAME, INSERM UMR1137, Paris, France; Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Paris, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
authors.affiliation: Institut Pasteur, Unité HIV Inflammation et Persistance, Paris, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Angin
authors.affiliation: Institut Pasteur, Unité HIV Inflammation et Persistance, Paris, France.
authors.forename: Annie
authors.initials: A
authors.lastname: David
authors.affiliation: Laboratoire d'Immunologie, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France; INSERM UMR1149, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Caillat-Zucman
authors.affiliation: IAME, INSERM UMR1137, Paris, France; Laboratoire de Pharma-Toxicologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.affiliation: Service d'Hématologie et Oncologie pédiatriques, Assistance Publique-Hôpitaux de Paris, Hôpital Trousseau, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dollfus
authors.affiliation: INSERM U1018, Université Paris Sud, Le Kremlin Bicêtre, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Le Chenadec
authors.affiliation: INSERM U1018, Université Paris Sud, Le Kremlin Bicêtre, France; Service d'Epidémiologie et de Santé publique, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicêtre, France.
authors.forename: Josiane
authors.initials: J
authors.lastname: Warszawski
authors.affiliation: Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France; EA7327, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.affiliation: Institut Pasteur, Unité HIV Inflammation et Persistance, Paris, France. Electronic address: asier.saez-cirion@pasteur.fr.
authors.forename: Asier
authors.initials: A
authors.lastname: Sáez-Cirión
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005602:France; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy* / Q000821:virology; D055502:Secondary Prevention; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D019380:Anti-HIV Agents