title: Structured interruptions of highly active antiretroviral therapy in cycles of 4 weeks off/12 weeks on therapy in children having a chronically undetectable viral load cause progressively smaller viral rebounds.
abstract: OBJECTIVE
  To evaluate the viral, immune and clinical impact of a structured treatment interruption (STI) program of highly active antiretroviral therapy (HAART) in three cycles of 4 weeks off/12 weeks on therapy in a cohort of children with HIV infection under chronic viral control.
  
  
  METHODS
  Using a single-group time series experimentation design and following informed consent, the HAART of children with HIV and a chronically undetectable viral load (VL) was discontinued for 4 weeks and then restarted and continued for 12 weeks for a total of three cycles. The VL, CD4+/CD8+ lymphocytes, and clinical status were evaluated at the end of each STI and at 6 and 12 weeks after HAART was resumed.
  
  
  RESULTS
  Four children with a median age of 10.3 years (range 6.5-11.2 years) were included in the study. Their clinical immune categories were: A1 (n=2), A2 (n=1), and B3 (n=1). Treatment of all four patients was with zidovudine (AZT)+lamivudine (3TC)+ritonavir (RTV). At the end of the first STI, VL was a median 214000 copies/ml (range 27400-616000), corresponding to 5.3 log(10) (range 4.4-5.8). At the end of the second STI, VL was a median 72400 copies/ml (range 17800-126000) or 4.7 log(10) (range 4.2-5.1), which corresponds to a rebound 0.6 log(10) lower than the first. At the end of the third STI, VL was a median 28200 copies/ml (range 5370-140000) or 4.45 log(10) (range 3.7-5.1), a rebound 0.85 log(10) lower than the first. All rebounds were followed by a decrease in the VL to undetectable levels during the treatment periods. CD8+ T lymphocyte counts increased during viral rebounds and an initial decrease in CD4+ T lymphocyte counts was followed by a tendency to increase even exceeding CD8+ T cell counts. Only one event of transitory severe immunosuppression occurred. There were no symptoms related to the HIV infection.
  
  
  CONCLUSIONS
  The STI of HAART in cycles of 4 weeks off/12 weeks on therapy in children with chronically undetectable VL can cause progressively lower viral rebounds followed by a decrease to undetectable levels, with a low risk of severe immunosuppression and without the occurrence of symptoms related to HIV.
authors.affiliation: Departamento de Pediatria and Infectologia Pediatrica, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 25 and Centro de Investigacion Biomedica del Noreste, Instituto Mexicano del Seguro Social, Fidel Velasquez y Lincoln S/N, Colonia Nueva Morelos, Monterrey, Nuevo Leon, CP 64320, Mexico. palsaugc@gmail.com
authors.forename: Gerardo C
authors.initials: GC
authors.lastname: Palacios
authors.forename: Luz M
authors.initials: LM
authors.lastname: Sanchez
authors.forename: Evangelina
authors.initials: E
authors.lastname: Briones
authors.forename: Teresa J
authors.initials: TJ
authors.lastname: Ramirez
authors.forename: Hugo
authors.initials: H
authors.lastname: Castillo
authors.forename: Lydia G
authors.initials: LG
authors.lastname: Rivera
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Vazquez
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodriguez-Padilla
authors.forename: Mark
authors.initials: M
authors.lastname: Holodniy
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D002648:Child; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D016896:Treatment Outcome; D019562:Viral Load; D028761:Withholding Treatment
chemical_list: D019380:Anti-HIV Agents