TY - JOUR
T1 - Efficacy, tolerability and pharmacokinetics of two nelfinavir-based regimens in human immunodeficiency virus-infected children and adolescents
T2 - Pediatric AIDS Clinical Trials Group Protocol 403
AU - King, Jennifer R.
AU - Nachman, Sharon
AU - Yogev, Ram
AU - Hodge, Janice
AU - Aldrovandi, Grace
AU - Hughes, Michael D.
AU - Chen, Jie
AU - Wiznia, Andrew
AU - Damle, Bharat
AU - Acosta, Edward P.
N1 - Funding Information:
Supported by grants UO1 AI41089 (UAB) and the Pediatric AIDS Clinical Trials Group of the National Institutes of Allergy and Infectious Disease.
PY - 2005/10
Y1 - 2005/10
N2 - 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.
AB - 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.
KW - Antiretrovirals
KW - Children
KW - Human immunodeficiency virus
KW - Pharmacokinetics
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UR - http://www.scopus.com/inward/citedby.url?scp=26944466328&partnerID=8YFLogxK
U2 - 10.1097/01.inf.0000180508.21918.8a
DO - 10.1097/01.inf.0000180508.21918.8a
M3 - Article
C2 - 16220085
AN - SCOPUS:26944466328
SN - 0891-3668
VL - 24
SP - 880
EP - 885
JO - Pediatric Infectious Disease Journal
JF - Pediatric Infectious Disease Journal
IS - 10
ER -