About this trial
A longitudinal study with four parallel cohorts with each participant followed for 2 years: two cohorts in Busia (high malaria transmission site) and two cohorts in Kampala (low malaria transmission). Each site will have a cohort of children living with HIV (CLHIV) and HIV- uninfected children and will be age-matched, enrolled in parallel, and followed for two years. All children will be enrolled without malaria infection, as determined by a negative blood smear at baseline.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Agreement to come to the clinic for all follow-up evaluations
Provision of informed consent and assent (as appropriate)
Residency within approximately 30 km of the study clinic
Negative blood smear for malaria (all sites)
Disqualifiers
Significant comorbidities such as malignancy, active TB, chronic/active hepatitis B/C, diabetes, severe acute malnutrition, mitochondrial disorders
Receipt of known CYP interacting drugs at enrolment (except HAART) - see list of disallowed medications
Anemia defined by hemocue (Hb < 7.0) at the time of enrolment
Signs of uncomplicated or severe malaria at the time of enrollment
Trial design
Parallel
Treatments tested in this trial
Artemether-lumefantrine (AL)
DrugParticipants will receive the dispersible formulation of AL with contains 20 mg artemether, 120 mg of lumefantrine
artesunate-amodiaquine (AS-AQ)
DrugChildren will receive the tablet formulations of Artesunate Amodiaquine using weight based dosing
Treatment groups
Trial outcomes
Primary outcomes
Change in Body Mass Index (BMI)
Change in BMI from baseline and 2 years in kg/m² (Cohort 1 + 3 vs Cohort 2 + 4)
Drug pharmacokinetic (PK) exposure
Comparison of drug exposure by DTG and anti-malarial regimen using Area under the curve (AUC) (Cohort 1 vs 3)
Drug pharmacokinetic exposure
Comparison of drug exposure by DTG and anti-malarial regimen using Area under the curve (AUC) (Cohort 3 vs 4)
Recurrence rate of malaria
To assess the 28 and 42 day efficacy of AL and AS-AQ for the treatment of uncomplicated malaria in children with and without HIV.
Secondary outcomes
Average change in glucose sensor readings
Change in average of continuous glucose monitor readings over the last 10 days. (Cohorts 1 vs 2)
Change in insulin resistance (HOMA-IR)
Change in HOMA-IR in those living with and without HIV. (Cohorts 1+3 vs 2+4)
Change in Body Mass Index (BMI)
Change in BMI in children living with HIV from baseline and 2 years in kg/m² (Cohort 1 vs 3)
Pharmacokinetic parameters
AUC (0-8h) and AUC (last) for lumefantrine and DEAQ. (Cohorts 1 and 3)
Other outcomes
Time to resistance
Time to resistance mutation in days. (Cohort 3 and 4)
K13 mutations
Rate of K13 mutation and Artemisinin partial resistance. (Cohort 3 and 4)
Prevalence of mutations in malaria transporters
Change in mutation prevalence of pfcrt and pfmdr1 in those treated with AL vs AS-AQ for malaria.(Cohort 3 and 4)
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Yale University
Lead sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborator