Efficacy, tolerability and pharmacokinetics of two nelfinavir-based regimens in human immunodeficiency virus-infected children and adolescents: Pediatric AIDS Clinical Trials Group Protocol 403

Jennifer R. King*, Sharon Nachman, Ram Yogev, Janice Hodge, Grace Aldrovandi, Michael D. Hughes, Jie Chen, Andrew Wiznia, Bharat Damle, Edward P. Acosta

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Introduction: Few combinations of highly active antiretrovirals have been studied in nucleoside reverse transcription inhibitor (NRTI)-experienced, human immunodeficiency virus (HIV)-infected children. We tested the efficacy, tolerability and pharmacokinetics of 2 combination therapies containing an NRTI, protease inhibitors ± a nonnucleoside reverse transcription inhibitor (NNRTI). Methods: This was a phase II, randomized, multicenter study. Forty-one children and youths between 5 months and 21 years with prior NRTI and no prior NNRTI or protease inhibitor experience received either nelfmavir (NFV) 30 mg/kg twice daily (bid), ritonavir (RTV) 400 mg/m2 bid and buffered didanosine (ddl) 240 mg/m2 daily (arm A) or NFV 50-55 mg/kg bid, nevirapine (NVP) 120 mg/m2 bid and stavudine (d4T) 1 mg/kg bid (arm B). Patients were evaluated clinically for 48 weeks after initiation of therapy. Intensive pharmacokinetic sampling occurred after 4 weeks of therapy. Results: The proportion of children with HIV-1 RNA ≤400 copies/mL and on randomized treatment at 48 weeks was 65% among children assigned NFV + RTV + ddI versus 28% among those assigned NFV + NVP + d4T (P = 0.039). No significant difference in median CD4% change from baseline to week 48 was found (3% versus 1%). No significant differences in safety or tolerability between children randomized to NFV + RTV + ddI versus NFV + NVP + d4T were identified. However, a trend toward a higher rate of permanent discontinuation of study treatment was noted among children assigned to NFV + NVP + d4T compared with NFV + RTV + ddI [7 of 20 (35%) versus 2 of 21 (10%); P = 0.12]. NFV pharmacokinetic measurements were not statistically different between the treatment groups, yet exposure to the NFV metabolite, M8, was significantly higher in subjects receiving RTV. The pharmacokinetics for NVP, RTV and d4T were similar to those of previously reported data. Conclusion: Combination therapy containing NFV + RTV + ddI appears more efficacious in NRTI-experienced children than a regimen containing NFV + NVP + d4T. Differences in tolerability between the 2 treatment groups were not identified. Systemic exposure of these drugs was similar to that reported in other HIV-infected children and adults.

Original languageEnglish (US)
Pages (from-to)880-885
Number of pages6
JournalPediatric Infectious Disease Journal
Volume24
Issue number10
DOIs
StatePublished - Oct 2005

Keywords

  • Antiretrovirals
  • Children
  • Human immunodeficiency virus
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Efficacy, tolerability and pharmacokinetics of two nelfinavir-based regimens in human immunodeficiency virus-infected children and adolescents: Pediatric AIDS Clinical Trials Group Protocol 403'. Together they form a unique fingerprint.

Cite this