EDCTP portfolio: Neglected infectious diseases

The EMPIRICAL study is exploring whether a greater emphasis on treatment of TB and cytomegalovirus improves survival of young children with HIV.

Enhancing treatment of respiratory infections in HIV-infected infants

In 2016, around 160,000 children became infected with HIV, and more than 90% of HIV-infected children live in sub-Saharan Africa. Young children are particularly vulnerable to HIV infection – death rates are highest for HIV-infected children less than four years of age.

Respiratory tract infections are the main cause of death of children with HIV. WHO guidelines recommend treatment with antibiotics against common bacteria and the opportunistic pathogen Pneumocystis jirovecii, but mortality remains very high.

The challenge

Evidence has emerged that TB and cytomegalovirus – a common virus that only rarely causes disease – are major unrecognised causes of death in children infected with HIV. Each may account for up to 20% of deaths.

As diagnostics for these infections are generally not available in resource-poor settings, the EMPIRICAL trial is evaluating whether empirical treatment against TB and cytomegalovirus improves survival of HIV-infected infants with severe pneumonia.

HIV-infected infants aged between one month and 12 months will receive the usual pneumonia treatment of antibiotics, cotrimoxazole and prednisolone. Those thought to have a TB infection will receive anti-TB treatment, and half will also be given an antiviral, valganciclovir. Those not thought to have TB will randomly receive either valganciclovir or anti-TB treatment, on top of the usual pneumonia treatment. Survival will be compared at 15 days and after a year. 

The project

The EMPIRICAL study will determine whether empirical treatment of TB and cytomegalovirus reduces pneumonia mortality in young HIV-infected infants – who currently have the worst survival of all age groups.

Impact


test the safety and efficacy of this new formulation in young children

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

In 2016, around 160,000 children became infected with HIV, and more than 90% of HIV-infected children live in sub-Saharan Africa. Young children are particularly vulnerable to HIV infection – death rates are highest for HIV-infected children less than four years of age.

Respiratory tract infections are the main cause of death of children with HIV. WHO guidelines recommend treatment with antibiotics against common bacteria and the opportunistic pathogen Pneumocystis jirovecii, but mortality remains very high.

Evidence has emerged that TB and cytomegalovirus – a common virus that only rarely causes disease – are major unrecognised causes of death in children infected with HIV. Each may account for up to 20% of deaths.

As diagnostics for these infections are generally not available in resource-poor settings, the EMPIRICAL trial is evaluating whether empirical treatment against TB and cytomegalovirus improves survival of HIV-infected infants with severe pneumonia.

HIV-infected infants aged between one month and 12 months will receive the usual pneumonia treatment of antibiotics, cotrimoxazole and prednisolone. Those thought to have a TB infection will receive anti-TB treatment, and half will also be given an antiviral, valganciclovir. Those not thought to have TB will randomly receive either valganciclovir or anti-TB treatment, on top of the usual pneumonia treatment. Survival will be compared at 15 days and after a year. 

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The EMPIRICAL study will determine whether empirical treatment of TB and cytomegalovirus reduces pneumonia mortality in young HIV-infected infants – who currently have the worst survival of all age groups.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M

About us

The European & Developing Countries Clinical Trials Partnership (EDCTP) is a public–public partnership between 14 European and 16 African countries, supported by the European Union. EDCTP’s vision is to reduce the individual, social and economic burden of poverty-related infectious diseases by affecting sub-Saharan Africa. EDCTP’s mission is to accelerate the development of new or improved medicinal products for the identification, treatment and prevention of infectious diseases, including emerging and re-emerging diseases, through pre- and postregistration clinical studies, with emphasis on phase II and III clinical trials. Our approach integrates conduct of research with development of African clinical research capacity and networking. The second EDCTP programme is implemented by the EDCTP Association supported under Horizon 2020, the European Union’s Framework Programme for Research and Innovation.

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