title: Comparison of ritonavir plus saquinavir- and nelfinavir plus saquinavir-containing regimens as salvage therapy in children with human immunodeficiency type 1 infection.
abstract: BACKGROUND
  In this retrospective study we compared the antiretroviral effect of regimens consisting of simultaneous administration of two protease inhibitors (PI) with at least one nucleoside reverse transcriptase inhibitor on plasma viral load (VL) and CD4 cell count in HIV-infected children intensively pretreated with nucleoside reverse transcriptase inhibitors and PIs.
  
  
  METHODS
  Eleven HIV-infected children were changed to antiretroviral combination regimens including two PIs and followed for a median time of 24 weeks. Group A comprised six patients who were given ritonavir + saquinavir (SQV) and Group B consists of five patients who were changed to nelfinavir + SQV. Patients were treated with these combinations with 2 PIs because of treatment failure (increasing viral load) of prior PI therapy or clinical signs of disease progression.
  
  
  METHODS
  Serial determinations of plasma viral load (Amplicor, Roche) and CD4 cells were performed every 4 to 8 weeks. The detection limit of the Amplicor-reverse transcriptase-PCR assay was 50 copies/ml (1.7 log10).
  
  
  RESULTS
  In Group A the median VL reduction was 1.1 log10 after 3 months and 1.4 log10 after 6 months. In Group B median VL decreased 0.1 and 0.2 log10 after 3 and 6 months. In both groups during the study period none of the patients reached undetectable VL. The relative changes of CD4 cells above baseline in Group A showed a median increase of 7% after 3 months and 23% after 6 months. In Group B after 3 months CD4 cells did not increase, and after 6 months the median relative increase was only 7%. Both combination therapies were well tolerated, not necessitating any drug interruption during study period.
  
  
  CONCLUSIONS
  In children with intensive prior antiretroviral treatment, a salvage therapy including two PIs demonstrated antiretroviral efficacy in some patients. In this study the reduction of the VL as well as the increase of CD4 cells was more pronounced with ritonavir + SQV than with nelfinavir + SQV. With both combinations complete suppression of HIV replication was not achieved. Therefore the long term effect of these combinations may be limited by the emergence of resistant HIV strains.
authors.affiliation: Children's Hospital of the Ludwig Maximilians-University Munich, Germany. ida@KK-i.med.uni-muenchen.de
authors.forename: F
authors.initials: F
authors.lastname: Hoffmann
authors.forename: G
authors.initials: G
authors.lastname: Notheis
authors.forename: U
authors.initials: U
authors.lastname: Wintergerst
authors.forename: J
authors.initials: J
authors.lastname: Eberle
authors.forename: L
authors.initials: L
authors.lastname: Gürtler
authors.forename: B H
authors.initials: BH
authors.lastname: Belohradsky
mesh_terms: D000293:Adolescent; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D019888:Nelfinavir / Q000008:administration & dosage* / Q000009:adverse effects; D011379:Prognosis; D012189:Retrospective Studies; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects; D016879:Salvage Therapy; D019258:Saquinavir / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D017320:HIV Protease Inhibitors; D019888:Nelfinavir; D019258:Saquinavir; D019438:Ritonavir