Publications

18

Jul, 2004

Choice of first-line ART regimen in PENPACT 1: a randomized trial of combination antiretroviral regimens and treatment switching strategies in antiretroviral naive children >30 days and <18 years of age.

 

Authors: Gibb DM, Melvin A, Compagnucci A, McKinney R, Tudor-Williams G, Walker AS, Harper L, Hodge J, Powell C, Green H, Saïdi Y, Ortiz AA, Toye M, Girard S, Mofenson L, Giaquinto C, Hughes M on behalf of the PENPACT 1 Trial.

Published in: XV International AIDS Conference, 11-16 July 2004, Bangkok. Poster TuPeB4442.

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.

19

Apr, 2004

PENTA guidelines for the use of antiretroviral therapy 2004

 

Authors: Sharland M, Blanche S, Castelli G, Ramos J, Gibb DM for the PENTA Steering Committee.

Published in: HIV Med 2004; 5, (Suppl. 2), 61-86

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.

18

Apr, 2004

Maintaining the nelfinavir trough concentration above 0.8 mg/L improves virologic response in HIV-1-infected children

 

Authors: Burger DM, Bergshoeff A, de Groot R, et al; on behalf of the PENTA 5 study group.

Published in: J Paediatr 2004;145(3):403-405

Abstract Differences in virologic response were compared in 32 HIV-infected children with a nelfinavir trough concentration either below (n=7) or above (n=25) 0.8 mg/L. Virologic response at week 48 was observed in 29% of children with subtherapeutic nelfinavir troughs versus 80% in children with therapeutic nelfinavir troughs (P=.02)

18

Apr, 2004

Effect of concurrent zidovudine use on the resistance pathway selected by abacavir-containing regimens

 

Authors: Lanier ER, Givens N, Stone C, et al.

Published in: HIV Med. 2004;5(6):394-399

Objectives Abacavir (ABC) selects for four mutations (K65R, L74V, Y115F and M184V) in HIV‐1 reverse transcriptase (RT), both in vitro and during monotherapy in vivo. The aim of this analysis was to compare the selection of these and other nucleoside reverse transcriptase inhibitor (NRTI)‐associated mutations by ABC‐containing therapies in the presence and absence of concurrent lamivudine (3TC) and/or zidovudine (ZDV) and to assess the effect of these mutations on phenotypic susceptibility to the NRTIs.

Design This study was a retrospective analysis of the patterns of NRTI‐associated mutations selected following virological failure in six multicentre trials conducted during the development of ABC.

Methods Virological failure was defined as confirmed vRNA above 400 HIV‐1 RNA copies/mL. RT genotype and phenotype were determined using standard methods.

Results K65R was selected infrequently by ABC‐containing regimens in the absence of ZDV (13 of 127 patients), while L74V/I was selected more frequently (51 of 127 patients). Selection of both K65R and L74V/I was significantly reduced by co‐administration of ZDV with ABC (one of 86 and two of 86 patients, respectively). Y115F was uncommon in the absence (seven of 127 patients) or presence (four of 86 patients) of ZDV. M184V was the most frequently selected mutation by ABC alone (24 of 70 patients) and by ABC plus 3TC (48 of 70 patients). Thymidine analogue mutations were associated with ZDV use. The K65R mutation conferred the broadest phenotypic cross‐resistance of the mutations studied.

Conclusions The resistance pathway selected upon virological failure of ABC‐containing regimens is significantly altered by concurrent ZDV use, but not by concurrent 3TC use. These data may have important implications for the efficacy of subsequent lines of NRTI therapies.

 

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19

Feb, 2004

Pharmacokinetics (PK) of once daily versus twice daily Lamivudine and Abacavir in HIV-1 infected children: PENTA 13

 

Authors: Bergshoeff A, Burger D, Verweij C, Farrelly L, Flynn J, LeProvost M, Walker AS, Novelli V, Lyall H, Gibb DM.

Published in: 11th Conference of Retroviruses and Opportunistic Infections, San Francisco, 8-11 February 2004. Poster 934.

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