Paediatric programme - HIV and other diseases of poverty

Lead Research Organisation: MRC Clinical Trials Unit

Abstract

Our studies aim to improve management of children with severe illnesses of poverty (predominantly HIV, Malaria, bacterial infections, TB) worldwide. We have 20 years experience of HIV in children, inintially in Europe, now mainly in Africa. In Europe, prevention of mother-to-child HIV transmission has reduced new infections in babies, but many children are now entering adolescence. Our research is finding out the best medicines with the fewest longterm side-effects, as children have to take treatment for life. In UK, we are starting a new study (AALPHI) to find out how HIV and its treatment affects young people entering adulthood. |Rollout of HIV treatment in Africa is increasing, bringing many questions about how best to do this in countries with few trained staff or health infrastructure. HIV-infected children have many other problems including malnutrition, tuberculosis, bacterial infections, malaria; without treatment, ~50% die before their second birhtday. We are undertaking large studies with colleagues in south/east African countries aimed at providing ways to enable more children to access HIV treatment. |Throughout Africa, death from malaria and other severe infections is unacceptably high, most occurring <24 hours after admission to hospital. Little attention has been paid to resuscitation with fluids. We are working with colleagues in Kenya to find out the best way to resuscitate these very sick children, particularly with malaria.

Technical Summary

The CTU paediatric programme of trials and cohorts of childhood diseases of poverty - HIV, malaria, tuberculosis and sepsis - aims to generate evidence to inform policy and practice in both well-resourced and resource-limited countries worldwide, particularly Africa. |The PENTA (Paediatric European Network for treatment of AIDS, www.pentatrials.org) program (funding EU 1990-2015) undertakes cohorts and trials in ~15 countries in Europe, South America, Asia(Thailand) and Africa (Uganda) addressing questions on HIV-infection in children which cannot be extrapolated or assumed from adult studies. New trials aimed at older children/adolescents focus on strategies to maximise efficacy and adherence to antiretroviral therapy (ART) while minimising longterm toxicity (PENTA 16, 18 & 20 trials). Two trials recently completed: (1)PENTA 11, a trial of CD4-guided treatment interruptions (AIDS 2010) has 5 year follow-up ongoing; (2)PENPACT1: a 5-year trial of what treatment to start and when to switch will be presented at World AIDS 2010. |Individual patient meta-analyses of European cohort data address multiple questions, including informing trial design, facilitating recruitment and longterm follow-up during/after trials, comparisons between adults and children and pharmcovigilance information for the EMEA. The Childrens HIV Paediatric Study (CHIPS, a UK/Irish paediatric HIV cohort, www.chipscohort.org, DOH funding 1990-), contributes to the above and also provides annual feedback to inform national paedaitric HIV services. Recently (2012) a new cohort study of HIV-infected adolescents and HIV-negative controls has started recruitment. It will evaluate long-term health outcomes in these two groups, with a particular focus on neurodevelopment, quality of life and growth. |In Africa, large ongoing trials in Uganda, Zambia, Zimbabwe and South Africa (total ~2,500 children) are addressing multiple management questions including: when to start ART in children; when and whether ART can be stopped after early treatment; how to monitor children on ART; simplification of ART using fixed dose combination baby pills and once-daily dosing; whether cotrimoxaozole prophylaixs can be stopped in children on ART. Several trials have 2 or more randomisations (in factorial design), have multiple substudies (e.g. pharmacokinetics, adherence, co-morbidities tuberculosis, sepsis, malnutirition) and include additional social science and economic components. A new trial addressing ways to reduce early mortality in HIV-infected adults and children is planned. |In collaboration with Wellcome Trust centre, Kilifi, Kenya, FEAST (www.Feast.org, 2009-2011) is a large (3,600) pragmatic trial evaluating fluid resuscitation strategies in sick children in Uganda, Tansania and Kenya, predominantly due to malaria and sepsis. CTU plays a key role in design, analysis and mentoring. A new trial evaluating transfusion, antibiotic and prophylaxis strategies in sick anaemic children coming into hospital is in the planning stages (TRACT trial).

Publications

10 25 50
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American Academy Of Pediatrics Committee On Pediatric AIDS, Section On International Child Health (2007) Increasing antiretroviral drug access for children with HIV infection. in Pediatrics

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Burger DM (2007) Age-dependent pharmacokinetics of lamivudine in HIV-infected children. in Clinical pharmacology and therapeutics

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Bwakura-Dangarembizi M (2014) A randomized trial of prolonged co-trimoxazole in HIV-infected children in Africa. in The New England journal of medicine

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Chakraborty R (2008) HIV-1 drug resistance in HIV-1-infected children in the United Kingdom from 1998 to 2004. in The Pediatric infectious disease journal

 
Description Antiretroviral Therapy of HIV Infection in infants and Children in Resource-Limited Setttings: Towards Universal Access. Recommendations for a public health approach
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
 
Guideline Title PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection
Description Citation in PENTA guidelines
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact CHIPS data contributed evidence to the section describing testing strategies for children newly arriving within the EU and presenting to health services
URL http://www.pentatrials.org/guide09.pdf
 
Guideline Title Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. August 16, 2010. Department of Health and Human Services, USA.
Description Citation in US guidelines
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact CHIPS data contributed epidemiological data to assess the general nature of problems in clinical management of HIV in paediatrics, as well as specifically contributing evidence to inform guidance on the use of tenofovir in paediatrics; PENTA trials have contributed to evidence for firstline therapy;cohort collaborations including CHIPS and PENTA data form the mainstay of when to start treatment according to age-related CD4 counts and percentages for US guidelines, as well as PENTA and WHO guidelines.
 
Description Core Member of WHO consolidated ARV Guidelines 2013
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
 
Description DART Trial Film
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Provides evidence that toxcicity monitoring is not required for ARV's in WHO 2010 ARV Guidelines.
 
Guideline Title Draft recommendations for management of children with severe febrile illness and impaired circulation without signs of severely impaired circulation
Description East Africa Guidelines Panel Recommendations
Geographic Reach Africa 
Policy Influence Type Citation in clinical guidelines
 
Description FEAST Trial Film
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Although WHO Guidelines have not yet changed, practice has changed in the centres who participated in the trial and there ahs been widespread international discussion about these results.
 
Guideline Title Antiretroviral Therapy of HIV Infection in infants and Children in Resource-Limited Setttings: Towards Universal Access. Recommendations for a public health approach.
Description Generating evidence for when to start treatment for HIV-infected children
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact Formed the basis of when to start ART in guidelines in US, WHO, Europe and then National guidelines. CHER trial results (2007) informed WHO 2008 guidelines on early treatment of infants. results of HPPMCS cohort collaboration informed start treatment guidelines for children after infancy
URL http://www.who.int/hiv/pub/guidelines/WHOpaediatric.pdf
 
Guideline Title WHO Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach
Description Influence on WHO ART guidelines 2013
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
 
Guideline Title Management of circulatory failure in normally nourished children
Description MSF shock algorithms
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
 
Description Member of WHO Maternal and Child Health Guideline Development Group
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
 
Description Membership of PENTA Guidelines
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
Impact referred to by practitioners and national paedaitric guideline bodies worldwide
 
Description Paediatric Medicines Expert Advisory Group to the MHRA
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact Advises about paediatric medicines for the MHRA
 
Description WHO 2006, 2007, 2008, 2010 World Health Organisation Guidelines Committee for Paedaitric Antiretroviral therapy
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
Impact WHO guidelines set the standard for HIV treatment in resource-limited settings
 
Description WHO Expert advisory group on formulations of antiretroviral drugs for children
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact Development of weightband-based dosing tables of antiretroviral drugs, including fixed dose combination drugs for HIV-infected children in resource-limited countries. Used to approach generic companies to make these products and widely used in resource-limited settings. We have provided much of the evidence on which these recommendations are based from pharmacokinetic and other studies
 
Description WHO expert consultation for global recommendations on cotrimoxazole prophylaxis for HIV infection in adults and children, Geneva
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
Impact accepted as the evidence base for cotrimoxazole prophylaxis in adults and children with HIV infection in resource-limited settings worldwide. incorporated into most national guidelines
 
Guideline Title WHO consolidated guidelines 2013
Description WHO guidelines - health economics and modelling
Geographic Reach Africa 
Policy Influence Type Citation in clinical guidelines
URL http://apps.who.int/iris/bitstream/10665/93523/1/WHO_HIV_2013.61_eng.pdf
 
Guideline Title WHO consolidated ART guidelines
Description WHO guidelines 2013 - health economics and modelling
Geographic Reach Africa 
Policy Influence Type Citation in clinical guidelines
URL http://apps.who.int/iris/bitstream/10665/91043/1/WHO_HIV_2013.60_eng.pdf
 
Guideline Title WHO consolidated ART guidelines 2013
Description WHO guidelines 2013 - health economics and modelling
Geographic Reach Africa 
Policy Influence Type Citation in clinical guidelines
URL http://apps.who.int/iris/bitstream/10665/93524/1/WHO_HIV_2013.56_eng.pdf
 
Description A multi-centre randomised controlled trial of volume expansion in children with severe malaria (FEAST)
Amount £2,144,054 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 01/2007 
End 01/2012
 
Description A randomized controlled trial of shorter course treatment for uncomplicated minimal childhood tuberculosis (SHINE)
Amount £3,217,996 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2014 
End 10/2018
 
Description Adolescents and Adults Living with Perinatal HIV cohort (AALPHI)/ Monument Trust (Sainsbury Family)
Amount £850,000 (GBP)
Organisation The Sainsbury Family Charitable Trusts 
Department Monument Trust
Sector Charity/Non Profit
Country United Kingdom
Start 08/2011 
End 12/2015
 
Description Alexander Flemming Dissemination Grant (FEAST)
Amount £30,000 (GBP)
Organisation Medical Research Council (MRC) 
Department Medical Research Foundation
Sector Charity/Non Profit
Country United Kingdom
Start 01/2011 
End 01/2012
 
Description Audit of Tenofovir in HIV infected children in UK/Gilead
Amount £36,637 (GBP)
Organisation Gilead Sciences, Inc. 
Department Gilead
Sector Private
Country United Kingdom
Start 06/2006 
End 09/2009
 
Description CHAPAS 3: Expanding the Availability of Fixed Dose Combination Antiretroviral Formulations for First-line Treatment of HIV-infected Children - the Children with HIV in Africa Pharmacokinetics and Acceptability/Adherence of Simple Antiretroviral Regimens
Amount € 4,617,034 (EUR)
Organisation Sixth Framework Programme (FP6) 
Department European and Developing Countries Clinical Trials Partnership
Sector Public
Country European Union (EU)
Start 01/2010 
End 01/2014
 
Description Children with HIV in Africa - Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS-1 trial)
Amount £319,534 (GBP)
Organisation Sixth Framework Programme (FP6) 
Department European and Developing Countries Clinical Trials Partnership
Sector Public
Country European Union (EU)
Start 01/2006 
End 01/2010
 
Description Children with HIV in Africa Pharmacokinetics and Acceptability/Adherence of Simple Antiretroviral Regimens CHAPAS-3 Trial/EDCTP
Amount £683,863 (GBP)
Organisation Sixth Framework Programme (FP6) 
Department European and Developing Countries Clinical Trials Partnership
Sector Public
Country European Union (EU)
Start 01/2009 
End 06/2013
 
Description Collaborative HIV Paediatric Study (CHIPS)/Department of Health
Amount £783,000 (GBP)
Organisation NHS England 
Sector Public
Country United Kingdom
Start 04/2010 
End 03/2019
 
Description DART Substudy: Follow-up of infants born to HIV infected women in the DART study/Gilead Sciences
Amount £52,800 (GBP)
Organisation Gilead Sciences, Inc. 
Department Gilead
Sector Private
Country United Kingdom
Start 09/2006 
End 12/2009
 
Description Development of Antiretroviral Therapy in Africa (Medical Research Fund - Alexander Fleming Dissemintion Scheme)
Amount £30,000 (GBP)
Organisation Medical Research Council (MRC) 
Department Medical Research Foundation
Sector Charity/Non Profit
Country United Kingdom
Start 11/2009 
End 06/2010
 
Description Does short cycle antiretroviral therapy impact on inflammation, immune activation, thrombogenesis and CD4 cell dynamics?
Amount £60,773 (GBP)
Funding ID 11/136/108 
Organisation National Institute for Health Research 
Department Health Technology Assessment Programme (HTA)
Sector Public
Country United Kingdom
Start 06/2013 
End 06/2015
 
Description European Network Treatment AIDS Laboratory Network (PENTA LABNET)
Amount £75,000 (GBP)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2007 
End 01/2012
 
Description MRC Training Fellowship - Felicity Fitzgerald
Amount £205,907 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2013 
End 09/2016
 
Description Network of Excellence: Task Force in Europe for Drug Development for the Young, (TEDDY) 4.4m euros across 18 participants
Amount £44,577 (GBP)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 06/2005 
End 06/2010
 
Description Networking Grant for Clinical Pharmacology in Sub Saharan Africa/The European & Developing Countries Clinical Trials Partnership
Amount £30,000 (GBP)
Organisation Sixth Framework Programme (FP6) 
Department European and Developing Countries Clinical Trials Partnership
Sector Public
Country European Union (EU)
Start 01/2007 
End 01/2014
 
Description Networking grant: Identifying the common learning needs of investigators working in poverty-related diseases in African settings, areas of project and data/The European & Developing Countries Clinical Trials Partnership
Amount £30,000 (GBP)
Organisation Sixth Framework Programme (FP6) 
Department European and Developing Countries Clinical Trials Partnership
Sector Public
Country European Union (EU)
Start  
 
Description Optimising Clinical Care, Treatment Strategies and Use of laboratories for ART Roll Out in Africa: The Lab-Lite Project
Amount £1,896,304 (GBP)
Organisation Government of the UK 
Department Department for International Development (DfID)
Sector Public
Country United Kingdom
Start 05/2011 
End 05/2015
 
Description PENTA 16 Trial: Short-Cycle Therapy (SCT) (5 days on/2 days off) in young people with chronic HIV-infection/Health Technology Assessment
Amount £531,261 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 01/2011 
End 01/2015
 
Description Paediatric European Network Treatment AIDS and European Collaborative Study on HIV infected pregnant women and their children: renewal of the PENTA Concerted Action
Amount £463,158 (GBP)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2006 
End 01/2010
 
Description Reduction of Early mortaLITY in HIV-infected African adults and children starting antiretroviral therapy: REALITY trial
Amount £3,986,746 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2012 
End 03/2018
 
Description Research Collaboration Agreement - PENTA/EPPICC
Amount £1,556,696 (GBP)
Organisation PENTA Foundation 
Sector Academic/University
Country France
Start 06/2011 
End 12/2017
 
Description Support for UK clinical centres enrolling in PENTA trials
Amount £67,648 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start  
End 03/2009
 
Description Support for enrolment of additional children into joint PENTA/PACTG Penpact 1 Trial/National Institute of Child Health and Human Development, USA
Amount £129,636 (GBP)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 01/2003 
End 01/2009
 
Description The Cost Effectiveness of Antiretroviral Therapy in the CHAPAS Trials/Development Corporation Ireland
Amount £60,000 (GBP)
Organisation Government of Ireland 
Department Development Corporation Ireland (DCI)
Sector Public
Country Ireland
Start  
 
Description The Cost Effectiveness of Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected African children in the CHAP trial/Development Corporation Ireland
Amount £60,000 (GBP)
Organisation Government of Ireland 
Department Development Corporation Ireland (DCI)
Sector Public
Country Ireland
Start 01/2006 
End 01/2010
 
Description Trial of Cotrimoxazole prophylaxis in HIV Infected Children in Zambia (CHAP) - including extension for microbiology and after-trial follow-up
Amount £479,000 (GBP)
Organisation Government of the UK 
Department Department for International Development (DfID)
Sector Public
Country United Kingdom
Start  
 
Description Wellcome Trust Fellowship Helen Payne (Immunology substudies in CHER Trial)
Amount £314,606 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2011 
End 07/2015
 
Description Wellcome Trust Fellowship Julia Kenny (CHAPAS 3 Trial & Substudies)
Amount £371,694 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2012 
End 07/2016
 
Description Young Lives: the Social Contexts of Paediatric Anti-Retroviral Therapy. A DFID Social Science programme in Uganda and Zimbabwe
Amount £788,800 (GBP)
Organisation Government of the UK 
Department Department for International Development (DfID)
Sector Public
Country United Kingdom
Start 01/2011 
End 01/2015
 
Title PENTA biobank 
Description central repository with web access and virtula database in France for all PENTA samples 
Type Of Material Database/Collection of Data/Biological Samples 
Provided To Others? No  
Impact ensuring rapid use of valuable clinical trial linked samples 
 
Title PENTA trials database 
Description Data collected for the ongoing trials 
Type Of Material Database/Collection of Data/Biological Samples 
Year Produced 2008 
Provided To Others? Yes  
Impact Data used in meta-analyses and in modelling 
 
Description Cipla 
Organisation Cipla
Country India 
Sector Private 
PI Contribution MRC CTU coordinated the CHAPAS 1,2,3 trials.
Collaborator Contribution Cipla have donated antiretroviral drugs for the children participating in these trials.
Impact The results of the CHAPAS 1 trial were used towards the licensing by the FDA of Triomune Baby/Junior Fixed Dose Formulations for children. CHAPAS 2 & 3 trials will provide data for licensing these important formulations for children in Africa.
Start Year 2006
 
Description DNDI (Drugs for Neglected Diseases Initiative) 
Organisation Drugs for Neglected Diseases initiative (DNDi)
Department Paediatric Programme
Country Switzerland 
Sector Charity/Non Profit 
PI Contribution MRC CTU co-ordinates the CHAPAS-2 trial.
Collaborator Contribution DNDI has funded the second cohort of the CHAPAS 2 trial and discussions are underway with Dr Marc Lallemant (Head of Paediatric HIV Programme) for further collaboration.
Impact Prof A Kekitiinwa, Principal Investigator at one of the Uganda sites for CHAPAS 2, was an invited speaker in a DNDI sponsored satelitte meeting on formulations for children at the AIDS 2012 Conference.
Start Year 2011
 
Description EPPICC (European Paediatric and Pregnancy HIV Cohort Collaboration) 
Organisation University of Padova
Country Italy 
Sector Academic/University 
PI Contribution We co-lead this network of paediatric observational HIV cohorts along with the Institute for Child Health. We have co-written the strategic plan for this network for the next 5 year period and have contributed to the EuroCoord bid which has secured funding for this network for the next 5 years.
Collaborator Contribution We are leading a new collaborative project (EPPICC infants) for this network, and the network has provided us with data to make the project feasible. The network also contributes epidemiological and clinical expertise to the project.
Impact Goetghebuer T, Haelterman E, Le Chenadec J, Dollfus C, Gibb D, Judd A, et al. Effect of early antiretroviral therapy on the risk of AIDS/death in HIV-infected infants. AIDS 2009,23:597-604. European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC). Fosamprenavir use in children in the European Union. A report to the European Medicines Agency (EMA), August 2009 (and repeated August 2010). London: MRC Clinical Trials Unit. European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC). Early antiretroviral therapy in HIV-1 infected infants in Europe, 1996-2008: treatment response and duration of first line regimens. AIDS. 2011;25:2279-2287.
Start Year 2007
 
Description Imperial College, London 
Organisation Imperial College London
Department Department of Paediatrics
Country United Kingdom 
Sector Academic/University 
PI Contribution Scientific leadership designing the TRACT (awarded £3,497,084 not yet started) and FEAST trials in collaboration with Professor Kath Maitland (Imperial College and KEMRI Wellcome Trust). Analysis and writing up of the FEAST trial; oversight of trial management and mentoring the trial team in Kilifi.
Collaborator Contribution Collaborators of the trial monitoring network in East Africa. The FEAST trial monitors also monitored the VITA trials in Tanzania. Dr Hermione Lyall was a Trial Steering Committee (TSC) member of the ARROW trial and is chair of the EndPoint Review Committe for CHAPAS 3. Dr Gareth Tudor-Williams is chair of the EndPoint Review Committee for ARROW. Clinical trial site for REALITY.
Impact The FEAST trial paper in NEJM, follow up papers ongoing. BMJ paper of the year 2012.
Start Year 2009
 
Description Kemri Wellcome Trust, Kilifi Kenya 
Organisation Wellcome Trust
Department KEMRI-Wellcome Trust Research Programme
Country Kenya 
Sector Multiple 
PI Contribution Scientific leadership designing the TRACT and FEAST trials in collaboration with Professor Kath Maitland (Imperial College and KEMRI Wellcome Trust). Analysis and writing up of the FEAST trial; oversight of trial management and mentoring the trial team in Kilifi. Chair of Trial Steering Committe of Cotrimoxizole trial for Jay Berkley.
Collaborator Contribution the CTU lead network of trial monitoring in East Africa. The FEAST trial monitors also monitored the VITA trials in Tanzania. Trial sites for REALITY Trial
Impact The FEAST trial paper in NEJM, follow up papers ongoing. BMJ paper of the year 2012.
Start Year 2009
 
Description National Institute of Health 
Organisation National Institutes of Health (NIH)
Country United States 
Sector Public 
PI Contribution Provide scientific input in to all aspects of desgin, analysis and write up of the CHER trial (Prof Diana Gibb and Prof Abdul Babiker). With Prof Lynne Mofenson at NIAID we have worked on PENPACT-1 trial and cohort collaborations (HPPMCS).
Collaborator Contribution We have collaborated with NIH who funded the CHER trial in South Africa through a CIPRA grant. NIH have contributed funding and collaboration on the PENPACT-1 trial
Impact Papers from the CHER trial and PENPACT-1 trial, papers from HPPMCS.
 
Description Radboud University Nijmegen Medical Centre, the Netherlands 
Organisation Radboud University Nijmegen Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution The research team at the MRC co-ordinates the ARROW, CHAPAS-1,2,3 and PENTA trials and provides scientific input and analysis of EDCTP funded VITA 1 and 2 trials.
Collaborator Contribution Long standing nesting of key pharmacokinetic studies within larger trial programmes. Contributed to several PhD studentships (all Dutch), PK data resulted in licensing of new appropriate antiretroviral formulations for children in resource limited settings.
Impact Radbound University has been involved in the analysis and writing up of the pharmacokinetics data from ARROW, PENTA 18 and the CHAPAS trials which has resulted in presentations at international conferences, peer review publications, FDA and EMA approval of drugs and Clinton Foundation and UNITAID dissemination in Africa.
Start Year 2007
 
Description University of Cape Town 
Organisation University of Cape Town
Department Division of Clinical Pharmacology
Country South Africa 
Sector Academic/University 
PI Contribution MRC CTU coordinates the CHAPAS 3, PENTA 17 (SMILE) and PENTA 20 (ODYSSEY) clinical trials.
Collaborator Contribution Dr Helen McIlleron's team designed, coordinate and analyse pharmacokinetic studies in collaboration with Prof David Burger from Nimejgen. Collaboration between MRC CTU at UCL, Harvard University and University of Cape Town to be Data Center for CIPHER global cohort collaboration. Clinical site for PENTA 17 (SMILE) and PENTA 20 (ODYSSEY) clinical trials
Impact Analyses of CHAPAS 3 data are currently in progress
Start Year 2010
 
Description University of York 
Organisation University of York
Department York Health Economics Consortium (YHEC)
Country United Kingdom 
Sector Academic/University 
PI Contribution MRC CTU coordinates programmes of trials and implementation projects.
Collaborator Contribution The Health Economics team led by Professor Mark Sculpher collaborate on cost effectiveness analyses linked to clincal trials and economic evaluations including equity and modelling for medical decision makers in health
Impact Paul Revill has led a cost effectiveness analysis of the ARROW data which is in the process of being published, he also leads a team of African economists (including capacity building working on the DFID funded Lablite project).
Start Year 2010
 
Title BREATHER - PENTA 16 
Description All young people enrolled in this clinical trial evaluating the role of Short Cycle Therapy (5 days on, 2 days off) in the management of HIV infection will be followed until July 2014. Young people continued to be followed on their randomised treatment, where appropriate, in a 2 year extended follow-up period until July 2016. Results were presented at CROI 2017 
Type Therapeutic Intervention - Drug
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2010
Development Status Closed
Clinical Trial? Yes
Impact Results were presented at CROI 2017. A further trial is planned to look at the possibility of a short course therapy in settings where viral loads are measured annually. 
URL http://pentatrials.org
 
Title CHAPAS 1 Trial - Triomune Baby/Junior 
Description Fixed Dose Combination Tablet of 3 antiretrovrials (Stavudine, Lamivudine, Nevirapine) 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2007
Development Status Closed
Clinical Trial? Yes
Impact Trial results contributed to tentative approval by FDA, which allowed use by Clinton foundation and other treatment programmes in Africa 
 
Title CHAPAS 2 Kaletra minitabs 
Description Lopinavir/Ritonavir in a novel minitabs sprinkle formulation have been developed by CIPLA Ltd. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2011
Development Status Under active development_distribution
Clinical Trial? Yes
UKCRN/ISCTN Identifier ISRCTN01946535
Impact CHAPAS 2 showed that minitabs were comparable with syrup in terms of pharmacokinetics and were more acceptable than syrups for younger children who are unable to take tablets. 
URL http://www.controlled-trials.com/ISRCTN01946535
 
Title CHAPAS 3 - Efavirenz double scored tablets 
Description Efavirenz 600mg tablets scored once on one side and twice on the other side have been developed by CIPLA Ltd to enable dosing using one tablet from childhood through to adulthood. These tablets have been evaluated in the CHAPAS 3 trial using weight band based dosing for pharmacokinetics and their acceptability to children and carers. These tablets are also now being used in the REALITY trial to treat both children and adults. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2012
Development Status Under active development_distribution
Clinical Trial? Yes
UKCRN/ISCTN Identifier ISRCTN69078957
Impact This product has the potential to greatly simplify ART provision to both adults and children 
URL http://www.controlled-trials.com/ISRCTN69078957
 
Title CHAPAS 3 ABC/3TC 120/60mg 
Description Abamune Junior 120/60mg is in the updated WHO 2013 guidelines for children as an urgently needed formulation. This product has been used in the CHAPAS 3 trial in which data on pharmacokinetics, adherance and acceptability has been collected 
Type Therapeutic Intervention - Drug
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2010
Development Status Under active development_distribution
Clinical Trial? Yes
UKCRN/ISCTN Identifier ISRCTN69078957
Impact This product will simplify dosing in children 
URL http://www.controlled-trials.com/ISRCTN69078957
 
Title Children with HIV Early Antiretroviral Therapy (CHER) 
Description evaluated early antiretroviral therapy in HIV infected infants in South Africa 
Type Management of Diseases and Conditions
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2011
Development Status Closed
Clinical Trial? Yes
Impact changed WHO guidance on when to start ART (2010) 
 
Title Children with HIV antibiotic prophylaxis 
Description randomised trial of Cotrimoxazole prophylaxis in Zambian children 
Type Therapeutic Intervention - Drug
Current Stage Of Development Late clinical evaluation
Development Status Closed
Clinical Trial? Yes
Impact changed WHO guidelines on Cotrimoxazole prophylaxis 
 
Title PENTA 11 - TICCH 
Description 5 year follow-up is continuing of children enrolled in PENTA 11 - a randomised study to evaluate CD4 driven planned treatment interruptions in children with HIV infection. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Late clinical evaluation
Development Status Under active development_distribution
Clinical Trial? Yes
Impact PENTA 11 and the CHER trial have provided randomised data for the possibility of planned treatment interruptions in HIV treatment. 
URL http://pentatrials.org
 
Title PENTA 18 - Once daily Kaletra 100/25ml 
Description Currently being analysed Kaletra 100/25ml paediatric tablets once daily in the KONCERT (PENTA 18) in process of submission to FDA 
Type Therapeutic Intervention - Drug
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2009
Development Status Closed
Clinical Trial? Yes
UKCRN/ISCTN Identifier ISRCTN02452400
Impact If lopinavir is shown to be non-inferior when taken once daily rather than twice daily in terms of virological suppression, we expect this will become the standard of care for this drug. 
URL http://www.pentatrials.org
 
Title SHINE Fixed dose combination TB treatment for children 
Description Fixed dose combination scored dispersable tablet, containing Isoniozid 50mg, rifampicin 75mg and pirozinamide 150mg for the intensive phase and an FDC tablet of isoniazid 50mg and rifampicin 75mg for the continuation phase. These are currently being evaluated in a bio equivalent study in healthy volunteers. If bioequivalent these will be used in SHINE. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Initial development
Year Development Stage Completed 2013
Development Status Under active development_distribution
Impact Still under development 
 
Description ARROW Cotrimoxazole film 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Film about the ARROW cotrimoxazole results released on YouTube.

161 views so far from the YouTube website. Unsure how many views from the MRC CTU website.
Year(s) Of Engagement Activity 2014
URL https://www.youtube.com/watch?v=D1n_We7x8Do
 
Description ARROW Cotrimoxazole policy brief 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/parliamentarians
Results and Impact The policybrief was distributed to policymakers in the Ministry of Health in Uganda and Zimbabwe (where the trial took place). It has also been more widely distributed at meetings, and is available on the MRC CTU website.

Feedback from policymakers at the Ministry of Health was very positive about the policy brief.
Year(s) Of Engagement Activity 2014
URL http://www.ctu.mrc.ac.uk/12602/13009/children_on_art_in_africa_need_to_continue_cotrimoxazole_prophy...
 
Description Aids Treatment Information Centre (ATIC) Newsletter on Development of New Paediatric Antiretroviral Formulations. CHAPAS-1 was used as a case study 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Primary Audience Health professionals
Results and Impact A newsletter that was distributed to healthcare providers throughout Uganda

The article was well received in Ugandan audience.
Year(s) Of Engagement Activity 2008
 
Description Anatomy of a clinical trial film 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact A film was developed, targeted at healthworkers, explaining the importance of clinical trials, using FEAST as an example. This film has been shown at a conference in South Africa, as well as being made available on YouTube and the MRC CTU website.

The film has had almost 500 views online. Health workers watching the film reported finding the interviews with the trial team before they found out the results, and watching them learn the results, to be very persuasive.
Year(s) Of Engagement Activity 2013
URL http://www.youtube.com/watch?v=GdMMuURsZQg&list=UUxUK9Zn4Es5SxMbAYeTSO2g
 
Description CHAPAS-1 participants meetings 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact The CHAPAS-1 centre held a participants day/celebration after the final Trial Steering Committee to feedback the results of the trial to participants. Presentations were done by trial staff.

Participants were very appreciative of being told results early in the dissemination process. Throughout the trial, regular meetings with participants enabled researchers to become aware of concerns and issues before these developed into major problems.
Year(s) Of Engagement Activity 2008
 
Description CHAPAS-1 policy briefs 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Primary Audience Policymakers/parliamentarians
Results and Impact A policy brief describing the main results of CHAPAS-1 and the advantages of fixed dose combination tablets for children.

The case studies were well received in Zambia and by African audience.
Year(s) Of Engagement Activity 2010
 
Description CHER long-term results press release 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact A press release was issued regarding the long-term results of CHER.

This was covered by an article on the AFP News wire.
Year(s) Of Engagement Activity 2013
 
Description CHIVA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Twice yearly contribution of lay text on the CHIPS study to the CHIVA Newsletter; yearly presentation of key findings from the CHIPS and AALPHI studies at the CHIVA national conference. Updating on results and ongoing PENTA trials

Improved reporting of patients to CHIPS, and general understanding of the CHIPS data and its importance. Recruitment of patients into PENTA trials
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description Communication Strategy for stakeholders (FEAST) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Health professionals
Results and Impact Communication Strategy was developed for the main stakeholders - including health professionals, policy makers and public. Primarily designed to raise awareness of the existance and potential impact of the trial.


Communities and hospitals were anxious to know the outcome of the study when published
Year(s) Of Engagement Activity 2009,2010,2011,2012
 
Description FEAST engagement with media over BMJ paper 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/parliamentarians
Results and Impact The story was covered by the Today Programme, BBC World Service, BBC News website, Guardian.

The World Health Organisation responded, saying they would release updated guidelines by the end of the year.
Year(s) Of Engagement Activity 2014
URL http://www.ctu.mrc.ac.uk/news/2014/current_septic_shock_treatment_guidelines_are_putting_childrens_l...
 
Description FEAST information pack 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact The information pack has been distributed to international policymakers including the World Health Organisation, international NGOs such as Medicins Sans Frontiers, and representatives of paediatric associations from ten African countries.

The implications of FEAST have been discussed by the paediatric associations of several African countries.
A small group is being convened to work on revising the ETAT and ETAT+ guidelines
Year(s) Of Engagement Activity 2012
 
Description Fluid Resuscitation Meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact Working with Kenya Paediatric Association we convened a workshop with representations from the paediatric associations of ten sub-Saharan African countries. This meeting looked at the evidence on fluid resuscitation of children, including that from the FEAST trial, and discussed the implications for policy and practice.

It was agreed that a small group would work on revising the ETAT and ETAT+ guidelines incorporating the evidence from FEAST. Participants in the meeting would also raise the issue with their national paediatric associations, with the aim of updating national policy.
Year(s) Of Engagement Activity 2012
 
Description Lablite briefing paper 1: prioritising improving laboratory monitoring or scaling up ART 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/parliamentarians
Results and Impact Briefing paper developed based on results of modelling study.

.
Year(s) Of Engagement Activity 2013
URL http://www.ctu.mrc.ac.uk/13706/13710/prioritising_increasing_access_to_art_or_improving_monitoring_o...
 
Description Lablite briefing paper: Access to lab tests 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/parliamentarians
Results and Impact Policy brief developed based on results of Lablite baseline survey. Currently being distributed.

Too early to say.
Year(s) Of Engagement Activity 2014
URL http://www.ctu.mrc.ac.uk/13706/13710/Access_to_lab_testing_at_primary_health_facilities
 
Description Lablite briefing paper: Children's access to ART 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Briefing paper developed based on results of Lablite baseline survey. Currently being distributed.

Currently being distributed.
Year(s) Of Engagement Activity 2014
URL http://www.ctu.mrc.ac.uk/13706/13710/Childrens_access_to_art
 
Description London Specialised Commissioning Group 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Annual production of a newsletter (annual report) and slide set which presents CHIPS data in lay language. Presentation of data at twice yearly London HIV Consortium meetings

CHIPS data are now used as the basis for commissioning paediatric HIV services across England, and are being developed to measure quality of services within new designation schemes.
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description PENTA Website 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact Includes detials of trials, updated news, publications, guidelines for antiretroviral therapy in children, links to HPPMCS risk calculator for clinicians, links to the CHIVA website,

regular traffic of emails asking questions and indicating appreciation
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description PENTA newsletters for participants 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Primary Audience Participants in your research and patient groups
Results and Impact regular newsletters update about ongoing trials and results

Appreciated by participants
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description Policy brief: Challenging fluid resuscitation for critically sick children in Africa (FEAST) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/parliamentarians
Results and Impact The policy brief, summarising the results of the FEAST trial, has been distributed to healthworkers and policymakers from ten African countries, and international agencies such as the World Health Organisation and Medicins Sans Frontiers.

Further copies of the policy brief have been requested (and sent) for distribution to Zambia Paediatric Association. The implications of FEAST have been discussed by the paediatric associations of several African countries.
Year(s) Of Engagement Activity 2012
 
Description Visit to WHO (FEAST) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Primary Audience Policymakers/parliamentarians
Results and Impact WHO awaiting results of trial. They would like to use the results and our expertise to advise of fluid management of the severely ill child

WHO are the key policy maker who advise on guidelines for management of children in LED countries including Africa. FEAST will direct inform policy.
Year(s) Of Engagement Activity 2010
 
Description talks/workshops to adolescents with HIV infection about research including understanding of clinical trials 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact eg workshop of >100 young people with HIV;

resulting in more active participation of young people with HIV in thinking about reserach
Year(s) Of Engagement Activity 2009,2010