Paediatric programme - HIV and other diseases of poverty

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.

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).