Publications

18

Jul, 2000

Nelfinavir doses should be increased in infants less than 3 months

 

Authors: Litalien C. Giaquinto C. Faye A. Mechinaud F. Grosch I. Compagnucci A. Jacqz-Aigrain E.

Published in: XIII International AIDS Conference July 9th-14th 2000, Durban, South Africa. Abstract Mo PEB 2213

PENTA 7 is a phase I/II multi-centre trial to evaluate the efficacy, safety and pharmacokinetics of nelfinavir, used in combination with didanosine and stavudine in HIV-infected infants of less than three months of age.

Vertically infected infants with very high viral load appear to be more at risk for rapid disease progression and so early treatment is recommended. There has been limited paediatric pharmacokinetic research for nelfinavir, but recent data suggests that older children (age range 3 months to 13 years) need doses (mg/kg) 2 to 4 times higher than adult doses to achieve similar plasma concentrations.

In this study the initial dose of nelfinavir was 40mg/kg TID (120mg/kg), but three months after its initiation, this was increased to 75mg/kg BID (150mg/kg) after the original dose failed to achieve therapeutic levels. Also BID dosing was implemented in line with adult studies showing comparable efficacy and better adherence with this schedule in comparison with TID. In addition didanosine and stavudine were given BID at doses of 100 mg/m2 and 1mg/kg respectively.

From September 1999 to February 2000, 9 pharmacokinetic studies were performed at steady state at least 2 weeks after initiation of the therapy on patients (N=8) aged between 1.5 and 7.2 months.

Important inter-patient variability was observed for Cmin and no correlation was found between this PK parameter and either the dose or the patient’s age. Only 2 patients (aged 5.7 and 2.6 months) were considered to have the equivalent of the desired adult minimum therapeutic Cmin value (Cmin ->1000ng/ml). And among the 5 patients aged less than 4 months, only infants receiving a daily dose range of 130 to 150 mg/kg/d achieved the adult target value for AUC. Indicating that infants less than 3 or 4 months need higher doses compared to adults and older children to achieve therapeutic concentrations.

19

Apr, 2000

Current evidence for the use of pediatric antiretroviral therapy – a PENTA analysis

 

Authors: Sharland M, Gibb DM, Giaquinto C.

Published in: European Journal of Pediatrics 2000; 159:649-656.

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19

Apr, 2000

Variable use of therpaeutic interventions for children with human immunodeficiency virus type 1 infection in Europe.

 

Authors: Bernardi S, Thorne C, Newell ML, Giaquinto C,Tovo PA, Rossi P.

Published in: European Journal of Pediatrics 2000; 159(3):170-5

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18

Apr, 2000

Reconstitution of the T-cell Pool in Treated, HIV-infected Children

 

Authors: King D, Gibb DM, Gotch F, Larsson-Sciard E.

Published in: 7th Conference on Retroviruses and Opportunistic Infections, January 30th- February 2nd, 2000, Abstract 322., San Francisco. Abstract 322

18

Apr, 2000

Immune repopulation after HAART in previously untreated HIV-1 infected children

 

Authors: Gibb DM, Newberry A, Klein N, de Rossi A, Grosch-Wörner I, Babiker A

Published in: Lancet.2000; 355: 1331-2

Abstract In 25 vertically HIV-infected children receiving highly-active antiretroviral therapy, a 3-log10 reduction in plasma HIV RNA load was maintained for 1 year and was associated with a doubling of the CD4-cell percentage. Most (75%) new CD4 cells carried the CD45RA marker of naive cells and there was only a small rise in memory cells (CD45RO). This pattern of immune restoration differs from adults, and may be due to the presence of a functioning thymus in children.

18

Apr, 2000

A randomised trial evaluating three NRTI regimens with and without Nelfinavir in HIV-infected children: 48 week follow-up from the PENTA 5 trial

 

Authors: Gibb. D. M. for the PENTA 5 Executive and the PENTA Steering Committee.

Published in: Oral presentation at 5th International Congress on Drug Therapy in HIV Infection, Glasgow 22-26 October 2000 also published in AIDS 2000, Vol 14, supp4 p.58 (abstractPL6.8)

18

Apr, 2000

Drug resistance in a trial of nucleoside analogue and protease inhibitor therapy in children (PENTA 5)

 

Authors: Kaye S. on behalf of the PENTA Virology Committee.

Published in: 5th International Congress on Drug Therapy in HIV Infection, October 22nd-26th 2000, Glasgow. P_308.

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