PENTA 7

18

Apr, 2007

Does Early Treatment Provide Long Term Benefit in HIV-1 Infected Infants? Five Year Outcomes in Children Treated Before 3 Months of Age in the PENTA 7 Trial.

 

Authors: Compagnucci A, Saïdi Y, Harper L, Blanche S, Gabiano C, de José Gomez I, Notheis G, Gibb DM, Giaquinto C and Faye A for the PENTA 7 committees

Published in: 14th Conference on Retroviruses and Opportunistic Infections, 25th-28th February 2007, Los Angeles. Poster 722 Abstract R -151 

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18

Jul, 2005

Lower scores of Nelfinavir metabolite M8 were associated with virological failure vertically infected children in the PENTA 7study.

 

Authors: Compagnucci A, Saïdi Y, Gibb DM, Rampon O, Ramos Amador JT, Feiterna Sperling C, Reliquet V, Giaquinto C, Navarro ML, Girard S, Harper L, Burger D, Treluyer JM, Aboulker JP, Jacqz-Aigrain E and Faye A on behalf of the PENTA 7 Study group.

Published in: 3rd IAS Conference on HIV Pathogenesis and Treatment, 24-27 July 2005, Rio de Janerio. Abstract MoPe9.2C15

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18

Jul, 2004

Three year outcomes in children treated with HAART before 3 months of age in the PENTA 7 trial.

 

Authors: Compagnucci A, Saïdi Y, Harper L, Navarro ML, Girard S, Walker AS, Debré M, Gibb DM, Rampon O, Lachassine E, Schmitz T, Giaquinto C, Aboulker JP, Fay

Published in: XV International AIDS Conference, 11-16 July 2004, Bangkok. Abstract B11956.

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17

Jun, 2004

Highly active antiretroviral therapy started in infants under 3 months of age: 72-week follow-up for CD4 cell count, viral load and drug resistance outcome

 

Authors: Aboulker JP, Babiker A, Chaix ML, et al; Paediatric European Network for Treatment of AIDS.

Published in: AIDS. 2004.23;18(2):237-45

Objective To assess the feasibility and impact of highly active antiretroviral therapy (HAART) started in vertically HIV-1-infected infants less than 3 months of age.
Methods Adverse events, plasma HIV-1 RNA, CD4 cell counts, CD4 cell percentage (CD4%) and clinical progression were recorded at baseline and prospectively to 72 weeks in order to assess the toxicity, tolerability and efficacy of a combination of stavudine, didanosine and nelfinavir. Selection of genotypic resistance was also investigated.
Results Twenty infants, of whom only three had Centers for Disease Control and Prevention stage B, initiated HAART at median age 2.5 months (range, 0.9-4.7) with median HIV-1 RNA concentration 5.5 log10 copies/ml (range, 3.2-6.8) and CD4% 33% (range, 11-66). Median follow-up was 96 weeks (range, 60-144). At week 72, 11 infants were still taking the original treatment. Few adverse events were reported related to treatment, all minor and causing treatment interruption in only three infants. No AIDS-defining events occurred; one child died of non-HIV-related causes (prematurity). All but two had CD4% > 25% at 72 weeks; however, 14 infants had virological failure and six acquired resistance mutations.
Conclusions Early treatment with stavudine, didanosine and nelfinavir was well tolerated and associated with good clinical and immunological outcomes at week 72. However, a high rate of virological failure with emergence of genotypic resistance is of great concern. More palatable drug combinations for infants and closer drug monitoring are required.

18

Apr, 2004

72-week follow-up of HAART started in infants aged less than 3 months: CD4, viral load and drug resistance outcomes in the PENTA 7 study

 

Authors: Writing Committee (alphabetical): Aboulker J-P, Babiker A, Chaix ML, Compagnucci A, Darbyshire JH, Debré M, Faye A, Giaquinto C, Gibb DM, Harper L, Saidi Y, Walker AS

Published in: AIDS 2004;18 (2):237-245

Objective To assess the feasibility and impact of highly active antiretroviral therapy (HAART) started in vertically HIV-1-infected infants less than 3 months of age.

Design A multicentre, phase I/II, non-randomized, open-label study (PENTA 7).

Methods Adverse events, plasma HIV-1 RNA, CD4 cell counts, CD4 cell percentage (CD4%) and clinical progression were recorded at baseline and prospectively to 72 weeks in order to assess the toxicity, tolerability and efficacy of a combination of stavudine, didanosine and nelfinavir. Selection of genotypic resistance was also investigated.

Results Twenty infants, of whom only three had Centers for Disease Control and Prevention stage B, initiated HAART at median age 2.5 months (range, 0.9-4.7) with median HIV-1 RNA concentration 5.5 log10 copies/ml (range, 3.2-6.8) and CD4% 33% (range, 11-66). Median follow-up was 96 weeks (range, 60-144). At week 72, 11 infants were still taking the original treatment. Few adverse events were reported related to treatment, all minor and causing treatment interruption in only three infants. No AIDS-defining events occurred; one child died of non-HIV-related causes (prematurity). All but two had CD4% > 25% at 72 weeks; however, 14 infants had virological failure and six acquired resistance mutations.

Conclusions Early treatment with stavudine, didanosine and nelfinavir was well tolerated and associated with good clinical and immunological outcomes at week 72. However, a high rate of virological failure with emergence of genotypic resistance is of great concern. More palatable drug combinations for infants and closer drug monitoring are required.

13

Jul, 2003

Impact of NFV and its active metabolite M8 trough levels on virologic response from primary HIV-1 vertically infected children treated with d4T, ddI and NFV in the PENTA 7 study.

 

Authors: Compagnucci A, Saidi Y, Faye A, et al.

Published in: 2nd IAS Conference on HIV Pathogenesis and Treatment, 13-16 July Paris. Poster 1095

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18

Apr, 2003

Pharmacokinetics of Nelfinavir and its Active Metabolite, hydroxy-tert-butylamide, in Infants Perinatally Infected with HIV-1.

 

Authors: Litalien C, Faye A, Compagnucci A, Giaquinto C, Harper L, Gibb DM, Jacqz-Aigrain E for PENTA.

Published in: Pediatr Inf Dis J 2003; 22(1):48-55

Background In children younger than 2 years of age vertically infected with HIV-1, the recommended pediatric dosing regimen for nelfinavir (20 to 30 mg/kg three times a day) provides insufficient drug exposure. This study was conducted to determine the steady state pharmacokinetics of nelfinavir and its active metabolite, M8, in this population.

Methods Fourteen infants (2.3 to 8.5 months) underwent 18 intensive pharmacokinetic studies of nelfinavir and M8 at steady state. Nelfinavir and M8 concentrations were measured by high performance liquid chromatography coupled with mass spectrometry, and individual pharmacokinetic values were determined.

Results A mean nelfinavir daily dose of 135.7 ± 18.8 mg/kg (twice or three times a day) resulted in median Cmin, Cmax, area under the plasma concentration-time curve (AUC0–24 h) and CL/ F for nelfinavir of 0.627 mg/l, 2.39 mg/l, 30.6 mg*h/l and 4.2 liters/h/kg, respectively. When normalized for a daily dose of nelfinavir of 150 mg/kg/day, 16.7% of Cmax and 27.8% of AUC0–24 h values were below the tenth percentile for adult values.

Conclusions During the first year of life, nelfinavir requirement is much higher than in older children and adults to obtain similar drug exposure. The mechanisms underlying such differences may involve higher first past metabolism and/or drug interactions or might be related to feeding conditions.

 

18

Feb, 2002

Difficulties in achieving suppression of viral replication in vertically HIV-1 infected infants early treated with d4T+ddI+NFV : The PENTA 7 Study.

 

Authors: Compagnucci A, Saidi Y, Chaix ML, et al.

Published in: 9th Conference on Retroviruses and Opportunistic Infections February 24-28, 2002 – Seattle. Poster 809 – W.

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18

Apr, 2001

Pharmacokinetics (PK) of Nelfinavir (NFV) and its Active Metabolite (M8) in Very Young Infants Infected with Human Immunodeficiency Virus (HIV)

 

Authors: Litalien C, Faye A, Compagnucci A, Jacqz-Aigrain E.

Published in: Pediatric Academic Societies 2001 Annual Meeting, April 28th – May 1st 2001, Baltimore MD. Abstract 2609.

18

Feb, 2001

Evaluation of Toxicity, Tolerability and Antiviral Activity of Early d4T+ddI+Nelfinavir (NFV) Therapy in HIV-1 Vertically Infected Infants : 24 Week Preliminary Results from the PENTA 7 Study

 

Authors: Faye A , Compagnucci A., Saidi Y; for the PENTA 7 Executive Committee

Published in: 8th Conference on Retroviruses and Opportunistic Infections, February 4th-8th, 2001, Chicago. Poster 678