Nov, 2009

PENTA 15: plasma pharmacokinetic study of once versus twice daily abacavir and lamivudine as part of combination antiretroviral therapy in HIV-1 infected children aged 3 to <36 months.


Authors: Jacqz-Aigrain, Farrelly L, Compagnucci A, Harrison L, Zhao W, Hamadache D, Welch S, Wintergerst U, Firtion G, Burger D

Published in: CROI 2009. February 8-11, 2009. Palais des Congres de Montreal, Canada , Poster S-154.



Jul, 2009

PENTA 15: Once-daily abacavir and lamivudine as part of combination antiretroviral therapy to 48 weeks in HIV-1 infected children aged 3 to 36 months.


Authors: Zhao W, Farrelly L, Compagnucci A, Harrison L, Jacqz-Aigrain E, Hamadache D, Welch S, Wintergerst U, Burger D on behalf of the PENTA Trial Steering Committee .

Published in: 1st International Workshop on HIV Pediatrics, 17 – 18 July 2009, Cape Town, South Africa



Jul, 2009

Adherence to ART and acceptability of planned treatment interruptions (PTI) in the PENTA 11 trial


Authors: Harrison L, Hamadache D, Bunupuradah T, Mazza A, Ramos Amador JT, Flynn J, Rampon O, Mellado Pena MJ, Floret D, Marczynska M, Puga A, Farrelly L, Riault Y, Lallemant M, Compagnucci A on behalf of the PENTA Trial Steering Committee.

Published in: 1st International Workshop on HIV Pediatrics, 17 – 18 July 2009, Cape Town, South Africa. (Poster P_90). 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Cape Town 19-22 July 2009



Apr, 2009

PENTA 2009 Guidelines for the use of Antiretroviral therapy in paediatric HIV-1 infection


Authors: Welch S, Sharland M, Lyall EG, et al.

Published in: HIV Med. 2009 Nov;10(10):591-613.

Abstract PENTA Guidelines aim to provide practical recommendations for treating children with HIV infection in Europe. Changes to guidance since 2004 have been informed by new evidence and by expectations of better outcomes following the ongoing success of antiretroviral therapy (ART). Participation in PENTA trials of simplifying treatment is encouraged. The main changes are in the following sections: ‘When to start ART’: Treatment is recommended for all infants, and at higher CD4 cell counts and percentages in older children, in line with changes to adult guidelines. The number of age bands has been reduced to simplify and harmonize with other paediatric guidelines. Greater emphasis is placed on CD4 cell count in children over 5 years, and guidance is provided where CD4% and CD4 criteria differ. ‘What to start with’: A three-drug regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) remains the first choice combination. Lamivudine and abacavir are the NRTI backbone of choice for most children, based on long-term follow-up in the PENTA 5 trial. Stavudine is no longer recommended. Whether to start with an NNRTI or PI remains unclear, but PENPACT 1 trial results in 2009 may help to inform this. All PIs should be ritonavir boosted. Recommendations on use of resistance testing, therapeutic drug monitoring and HLA testing draw from data in adults and from European paediatric cohort studies. Recently updated US and WHO paediatric guidelines provide more detailed review of the evidence base. Differences between guidelines are highlighted and explained.



Mar, 2009

Effect of early antiretroviral therapy on the risk of AIDS/death in HIV infected infants: the European Infant Collaborative Study.


Authors: Goetghebuer T, Haelterman E, Le Chenadec J, et al. for the European infant collaboration group.

Published in: AIDS 2009;23:597-604

Objective: In the absence of treatment, rapid progression to AIDS occurs in approximately 20% of HIV-1-infected infants over the first year of life. The prognosis of these children has considerably improved with highly active antiretroviral therapy. As data from well resourced countries are lacking, the objective of this collaborative study was to evaluate the impact of early treatment in vertically infected infants.

Design: Children born to HIV-infected mothers between 1 September 1996 and 31 December 2004, who were diagnosed with HIV and free of AIDS before 3 months, were eligible. Demographics and pregnancy data, details of antiretroviral therapy, and clinical outcome were collected from 11 European countries.Methods:The risk of AIDS or death, by whether or not an infant started treatment before 3 months of age, was estimated by Kaplan–Meier survival analysis and Cox proportional hazards models.

Results: Among 210 children, 21 developed AIDS and three died. Baseline characteristics of the 124 infants treated before 3 months were similar to those of the 86 infants treated later. The risk of developing AIDS/death at 1 year was 1.6 and 11.7% in the two groups, respectively (P < 0.001). Deferring treatment was associated with increased risk of progression [crude hazard ratio 5.0; 95% confidence interval (CI) 2.0–12.6; P = 0.001] that persisted after adjusting for cohort in multivariate models (adjusted hazard ratio 3.0; 95% CI 1.2–7.9; P = 0.021).

Conclusion: In HIV-1 vertically infected infants, starting antiretroviral therapy before the age of 3 months is associated with a significant reduction in progression to AIDS and death.



Feb, 2009

Effect of early antiretroviral therapy on the risk of AIDS/death in HIV-infected infants.


Authors: Goetghebuer T, Haelterman E, Le Chenadec J, Dollfus C, Gibb D, Judd A, Green H, Galli L, Ramos JT, Giaquinto C, Warszawski J, Levy J; for the European Infant Collaboration group.

Published in:  AIDS 2009 Feb



Nov, 2008

Treatment interruption in children with chronic HIV-infection: the results of the paediatric European network for treatment of AIDS (PENTA) 11 trial.


Authors: Gibb DM, Compagnucci A, Green H, Lallemant M, et al.

Published in: Journal of the International AIDS Society 2008, 11(Suppl 1):O21 (10 November 2008)


May, 2008

Plasma drug concentrations and virologic evaluations after stopping non-nucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1 infected children


Authors: Cressey TR, Green H, Khoo S, Treluyer J-M, Compagnucci A, Saidi Y, Lallement M, Gibb DM, Burger D.

Published in: Clin Infect Dis 2008. 15;46(10):1601-8 

Background The optimum strategy for stopping treatment with drugs that have different half-lives in a combination regimen to minimize the risk of selecting drug-resistant viruses remains unknown. We evaluated drug concentrations in plasma, human immunodeficiency virus (HIV) load, and development of drug resistance after a planned treatment interruption of a nonnucleoside reverse-transcriptase inhibitor (NNRTI)-containing regimen in HIV type 1-infected children.

Methods Children with viral loads <50 copies/mL and CD4 cell percentages > or =30% (for children aged 2-6 years) or CD4 cell percentages > or =25% and CD4 cell counts > or =500 cells/microL (for children aged 7-15 years) were randomized to either a planned treatment interruption or to continuous therapy. In the planned treatment interruption arm, either (1) treatment with nevirapine or efavirenz was stopped, and treatment with the remaining drugs was continued for 7-14 days, or (2) nevirapine or efavirenz were replaced by a protease inhibitor, and all drugs were stopped after 7-14 days. Sampling for determination of plasma drug concentrations, measurement of viral load, and drug resistance testing was scheduled at day 0, day 7 (drug concentrations only), day 14, and day 28 after interruption of treatment with an NNRTI.

Results Treatment with an NNRTI was interrupted for 35 children (20 were receiving nevirapine, and 15 were receiving efavirenz). Median time from NNRTI cessation to stopping all drugs was 9 days (range, 6-15 days) for nevirapine and 14 days (range, 6-18 days) for efavirenz. At 7 days, 1 (5%) of 19 and 4 (50%) of 8 children had detectable nevirapine and efavirenz concentrations, respectively; efavirenz remained detectable in 3 (25%) of 12 children at 14 days. At 14 days, viral load was > or =50 copies/mL in 6 of 16 children interrupting treatment with nevirapine (range, 52-7000 copies/mL) and in 2 of 12 children interrupting treatment with efavirenz (range, 120-1600 copies/mL). No new NNRTI mutations were observed.

Conclusions In children with virological suppression who experienced interruption of treatment with an NNRTI, staggered or replacement stopping strategies for a median of 9 days for nevirapine and 14 days for efavirenz were not associated with the selection of NNRTI resistance mutations.



Apr, 2008

A comparison of the rate of clinical disease progression in HIV-infected children and adults allowing for current CD4 cell count.


Authors: Dunn DT, Woodburn P, Duong T, Phillips AN, Gibb D, Porter K on behalf of HIV Paediatric Prognostic Markers Collaborative Study (HPPMCS) and the CASCADE Collaboration.

Published in: J Infect Dis 2008, 197:398-404



Feb, 2008

Marginal zone memory B-cell populations are irreversibly depleted in paediatric HIV infection.


Authors: Jacobsen MC, Thiebaut R, Fisher C, Sefe D, Clapson M, Klein NJ, Baxendale HE.

Published in: 5th Conference on Retroviruses and Opportunistic Infections, Boston, 2- 8 February 2008, Poster A-152 /453