title: Incidence of cancer in children perinatally exposed to nucleoside reverse transcriptase inhibitors.
abstract: BACKGROUND
  Long-term studies of tolerance to perinatal exposure to antiretroviral nucleoside reverse transcriptase inhibitors are required, in view of the potential genotoxicity of some of these molecules.
  
  
  OBJECTIVE
  To evaluate the incidence of cancers in uninfected children born to HIV-infected mothers.
  
  
  METHODS
  Cancers were detected in a nationwide prospective cohort of children born to HIV-infected mothers by standardized questionnaire during the prospective follow-up period of 2 years; thereafter, they were detected by spontaneous pharmacovigilance declaration and by crosschecking data with the national registries of childhood cancer. Standardized incidence ratio for incidence comparisons with general population.
  
  
  RESULTS
  Ten cases of cancer were detected among the 9127 exposed HIV-uninfected children (median age: 5.4 years, 53 052 person-years of follow-up). The overall incidence did not differ significantly from that expected for the general population: 10 cases observed versus 8.9 and 9.6 expected depending on whether 1990-1999 or 2000-2004 national rates were used as reference [standardized incidence ratio of 1.1 (0.3-1.5) and 1.0 (0.5-1.9)]. Five cases of central nervous system cancer were observed (standardized incidence ratio of 3.1 [1.0-7.2] P = 0.05 and 2.4 [0.8-5.6], P = 0.12). The relative risk of cancer for children exposed to didanosine-lamivudine combination was higher than that for zidovudine monotherapy [hazard ratio: 13.6 (2.5-73.9)].
  
  
  CONCLUSIONS
  This study did not evidence an overall increase in cancer risk in nucleoside reverse transcriptase inhibitor exposed children until 5 years of age. Results suggesting associations with specific nucleoside reverse transcriptase inhibitor combinations need further investigations. A longer surveillance, including differential analysis of the different cancer sites and various nucleoside reverse transcriptase inhibitors administered is warranted.
authors.affiliation: Inserm, U822, Le Kremlin-Bicêtre, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Benhammou
authors.forename: Josiane
authors.initials: J
authors.lastname: Warszawski
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bellec
authors.forename: François
authors.initials: F
authors.lastname: Doz
authors.forename: Nicolas
authors.initials: N
authors.lastname: André
authors.forename: Brigitte
authors.initials: B
authors.lastname: Lacour
authors.forename: Martine
authors.initials: M
authors.lastname: Levine
authors.forename: Françoise
authors.initials: F
authors.lastname: Bavoux
authors.forename: Roland
authors.initials: R
authors.lastname: Tubiana
authors.forename: Laurent
authors.initials: L
authors.lastname: Mandelbrot
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Clavel
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004812:Epidemiologic Methods; D005260:Female; D005602:France / Q000453:epidemiology; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008297:Male; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D011297:Prenatal Exposure Delayed Effects; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors