Prof. Pauline Byakika-Kibwika
Uganda
EDCTP portfolio: Senior Fellowships
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Professor Pauline Byakika-Kibwika is investigating how antiretroviral therapy affects the metabolism of antimalarial drugs.
Optimising malaria treatment for people living with HIV
Many populations with a high burden of HIV are also exposed to malaria. In addition, the two infections show reciprocal interactions – HIV infections leave people at greater risk of malaria, while malaria leads to increased viral replication.
Inevitably, therefore, many people are simultaneously treated for both HIV and malaria. Furthermore, treatments for both infections involve multiple drug combinations, increasing the risk of drug–drug interactions that affect their therapeutic effectiveness.
The challenge
Professor Pauline Byakika-Kibwika has been involved in studies revealing how antiretroviral drugs affect bloodstream levels of commonly used antimalarial combinations. In particular, efavirenz-based antiretroviral therapy has a significant impact on levels of artemether and its active metabolite, dihydroartemisinin, as well as those of its long-acting partner drug lumefantrine.
In her EDCTP Senior Fellowship, Professor Byakika-Kibwika is exploring the possible clinical implications of these drug–drug interactions, by monitoring outcomes of malaria treatment in people with HIV infections receiving antiretroviral therapy.
She is also undertaking pharmacokinetic studies to generate more data on the interactions between antiretroviral and antimalarial drugs.
The project
Professor Byakika-Kibwika’s Senior Fellowship project will reveal the clinical impact of drug–drug interactions between commonly used antimalarial and antiretroviral drugs. It will also identify the optimal dosage to overcome these interactions, which could then be evaluated in a formal clinical trial.
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
Many populations with a high burden of HIV are also exposed to malaria. In addition, the two infections show reciprocal interactions – HIV infections leave people at greater risk of malaria, while malaria leads to increased viral replication.
Inevitably, therefore, many people are simultaneously treated for both HIV and malaria. Furthermore, treatments for both infections involve multiple drug combinations, increasing the risk of drug–drug interactions that affect their therapeutic effectiveness.
Professor Pauline Byakika-Kibwika has been involved in studies revealing how antiretroviral drugs affect bloodstream levels of commonly used antimalarial combinations. In particular, efavirenz-based antiretroviral therapy has a significant impact on levels of artemether and its active metabolite, dihydroartemisinin, as well as those of its long-acting partner drug lumefantrine.
In her EDCTP Senior Fellowship, Professor Byakika-Kibwika is exploring the possible clinical implications of these drug–drug interactions, by monitoring outcomes of malaria treatment in people with HIV infections receiving antiretroviral therapy.
She is also undertaking pharmacokinetic studies to generate more data on the interactions between antiretroviral and antimalarial drugs.
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.
Professor Byakika-Kibwika’s Senior Fellowship project will reveal the clinical impact of drug–drug interactions between commonly used antimalarial and antiretroviral drugs. It will also identify the optimal dosage to overcome these interactions, which could then be evaluated in a formal clinical trial.
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