Title: Paediatric programme - HIV and other diseases of poverty
Funder: Medical Research Council

Abstract: 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).


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;6.1 PHARMACEUTICALS
Health categories: INFECTION