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document
Efficacy , tolerability and pharmacokinetics of two nelfinavir-based regimens in human immunodeficiency virus-infected children and adolescents : pediatric AIDS clinical trials group protocol 403 . 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 nelfinavir ( NFV ) 30 mg/kg twice daily ( bid ) , ritonavir ( RTV ) 400 mg/m bid and buffered didanosine ( ddI ) 240 mg/m daily ( arm A ) or NFV 50-55 mg/kg bid , nevirapine ( NVP ) 120 mg/m 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 < or =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 .
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Intervention_Pharmacological
nelfinavir-based
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Intervention_Pharmacological
antiretrovirals
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Intervention_Pharmacological
NRTI , protease inhibitors +/- a nonnucleoside reverse transcription inhibitor ( NNRTI )
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Intervention_Pharmacological
nelfinavir ( NFV ) 30 mg/kg twice daily ( bid ) , ritonavir ( RTV ) 400 mg/m bid and buffered didanosine ( ddI ) 240 mg/m daily ( arm A )
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Intervention_Pharmacological
NFV 50-55 mg/kg bid , nevirapine ( NVP ) 120 mg/m bid and stavudine ( d4T ) 1 mg/kg bid ( arm B )
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Intervention_Pharmacological
NFV
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Intervention_Pharmacological
RTV
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Intervention_Pharmacological
ddI
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Intervention_Pharmacological
NFV
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Intervention_Pharmacological
NVP
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Intervention_Pharmacological
d4T
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Intervention_Pharmacological
NVP
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Intervention_Pharmacological
RTV
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Intervention_Pharmacological
d4T
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Outcome_Other
Efficacy , tolerability and pharmacokinetics
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Outcome_Physical
median CD4 % change
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Outcome_Other
safety or tolerability
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Outcome_Other
permanent discontinuation of study treatment
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Outcome_Mental
tolerability