EDCTP portfolio: Neglected infectious diseases
index
The HAT-R-ACC study is assessing whether a new treatment is effective against a type of sleeping sickness mainly found in East Africa.
Treating East African sleeping sickness
Sleeping sickness (human African trypanosomiasis, HAT) is a parasitic disease that can be fatal without effective treatment. It is usually caused by a single-celled parasite, Trypanosoma brucei gambiense, but a relative, T. b. rhodesiense, can cause a similar but more acute disease (r-HAT). r-HAT is found mainly in East Africa, with Malawi and Uganda accounting for 88% of global infections.
Treatment of r-HAT has traditionally relied on either a toxic arsenic-based drug, melarsopol, or a less toxic but difficult-to-administer drug, suramin, depending on how far disease has progressed.
The challenge
Recently, a highly effective, safe oral treatment – fexinidazole – has been developed for HAT caused by T.b. gambiense. The HAT-R-ACC study will determine whether fexinidazole could also be adopted for treatment and control of r-HAT.
The HAT-R-ACC project will carry out a clinical trial to determine whether fexinidazole is a suitable alternative to replace both melarsopol and suramin at different stages of disease. The project will also work with local communities to raise awareness of the condition and treatment, and build local capacity to undertake scientific studies.
The project
The study will fill a major gap in knowledge on a rare but deadly disease having a significant regional impact, addressing an urgent WHO request for information on methods of r-HAT control in East Africa. Fexinidazole could also provide a key tool in the ultimate elimination of r-HAT in Africa.
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
Sleeping sickness (human African trypanosomiasis, HAT) is a parasitic disease that can be fatal without effective treatment. It is usually caused by a single-celled parasite, Trypanosoma brucei gambiense, but a relative, T. b. rhodesiense, can cause a similar but more acute disease (r-HAT). r-HAT is found mainly in East Africa, with Malawi and Uganda accounting for 88% of global infections.
Treatment of r-HAT has traditionally relied on either a toxic arsenic-based drug, melarsopol, or a less toxic but difficult-to-administer drug, suramin, depending on how far disease has progressed.
Recently, a highly effective, safe oral treatment – fexinidazole – has been developed for HAT caused by T.b. gambiense. The HAT-R-ACC study will determine whether fexinidazole could also be adopted for treatment and control of r-HAT.
The HAT-R-ACC project will carry out a clinical trial to determine whether fexinidazole is a suitable alternative to replace both melarsopol and suramin at different stages of disease. The project will also work with local communities to raise awareness of the condition and treatment, and build local capacity to undertake scientific studies.
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 study will fill a major gap in knowledge on a rare but deadly disease having a significant regional impact, addressing an urgent WHO request for information on methods of r-HAT control in East Africa. Fexinidazole could also provide a key tool in the ultimate elimination of r-HAT in Africa.
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