A Phase 4 interventional study of Artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ) in Malaria and Hiv, sponsored by Yale University. Recruiting at 2 sites in Uganda. Open to participants aged 5 Years to 17 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-02-04.
Sponsored by Yale University · Phase 4, Interventional, and Treatment
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.
CLHIV will be maintained on a dolutegravir (DTG) based regimen for >2 weeks prior to enrolment to ensure steady state. All children in Busia (HIV-infected and HIV-uninfected) will be enrolled and then randomized to receive either artemether- lumefantrine (AL) or artesunate-amodiaquine (AS-AQ) for each episode of malaria which occurs over longitudinal follow-up in year one. During year 1, they will continue to receive the same antimalarial each time they are treated for uncomplicated malaria. In year two, those children randomized to the AL arm will begin to receive an alternating regimen for each subsequent malaria episode (AS-AQ, then AL, then AS-AQ, etc..). If local/national guidelines in Uganda for malaria change during the course of the study, the treatment arms will be altered as applicable. Aim 1: To what extent does DTG impact, BMI, body composition and metabolic changes? Aims 2 and 3: Are there critical drug-drug interactions between DTG and first line artemisinin-based combination therapies (ACTs)? Do these changes impact HIV and malaria outcomes? What is the status of ACT resistance and its relationship to PK exposure?
MALARIA CASE DEFINITION:
Uncomplicated malaria (all of the following)
1,184 studies on the registry are indexed under Malaria; 79 are open to participants now.
This study's planned enrollment of 380 is above the median of 252 across 937 interventional studies indexed under Malaria.
Browse Malaria studies →Yale University is the lead sponsor of 1,770 studies on the registry; 294 are open to participants now.
Of its 221 completed or terminated interventional studies of FDA-regulated products, 129 (58%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
For Children and adolescents living with
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CLHIV on DTG living in the low transmission malaria setting of Kampala
Drug: Artemether-lumefantrine (AL) · Drug: artesunate-amodiaquine (AS-AQ)
HIV-uninfected children living in the low malaria transmission site of Kampala (control)
CLHIV on DTG living in the high malaria transmission site of Busia
Drug: Artemether-lumefantrine (AL) · Drug: artesunate-amodiaquine (AS-AQ)
HIV-uninfected children living in high malaria transmission site of Busia (control)
Participants will receive the dispersible formulation of AL with contains 20 mg artemether, 120 mg of lumefantrine
Children will receive the tablet formulations of Artesunate Amodiaquine using weight based dosing
Change in Body Mass Index (BMI)
Change in BMI from baseline and 2 years in kg/m² (Cohort 1 + 3 vs Cohort 2 + 4)
Time frame: baseline and 2 years
Drug pharmacokinetic (PK) exposure
Comparison of drug exposure by DTG and anti-malarial regimen using Area under the curve (AUC) (Cohort 1 vs 3)
Time frame: baseline up to 2 years
Drug pharmacokinetic exposure
Comparison of drug exposure by DTG and anti-malarial regimen using Area under the curve (AUC) (Cohort 3 vs 4)
Time frame: baseline up to 2 years
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.
Time frame: 28 days and 42 days
Average change in glucose sensor readings
Change in average of continuous glucose monitor readings over the last 10 days. (Cohorts 1 vs 2)
Time frame: every 6 months up to 2 years
Change in insulin resistance (HOMA-IR)
Change in HOMA-IR in those living with and without HIV. (Cohorts 1+3 vs 2+4)
Time frame: baseline and 2 years
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)
Time frame: baseline and 2 years
Pharmacokinetic parameters
AUC (0-8h) and AUC (last) for lumefantrine and DEAQ. (Cohorts 1 and 3)
Time frame: immediately post drug exposure (Day 1)
Change in HIV viral load
Change of HIV viral load suppression in those on DTG vs children not living with HIV. (Cohorts 1 vs 3)
Time frame: every 6 months up to 2 years
Malaria treatment outcome
28 and 42 day antimalarial treatment efficacy in those on DTG vs Children not living with HIV, as measured by peripheral blood smears
Time frame: 28 days and 42 days
HIV genotypic resistance to DTG
Resistance to DTG (binary measures as yes/no) as measured by HIV molecular genotype (Cohort 1 and 3)
Time frame: baseline and 2 years
Artemisinin PK concentration-time profile
Area under the plasma concentration versus time curve (AUC) in those receiving AL vs AS-AQ. (Cohorts 3 and 4)
Time frame: During treatment of malaria episodes over 2 years
Rate of parasite clearance
Parasite clearance half-life in those treated with AL vs AS-AQ. (Cohorts 3 and 4)
Time frame: During treatment of malaria episodes over 2 years
Rate of parasite clearance and HIV
Parasite clearance half-life in those living with HIV and those not living with HIV. (Cohorts 3 and 4)
Time frame: During treatment of malaria episodes over 2 years
Gametocyte quantity
Quantity of gametocytes in the peripheral blood in those treated artemisinin sensitive vs resistant infections. (Cohorts 3 and 4)
Time frame: At the time of presentation with malaria up to 2 years
Time to resistance
Time to resistance mutation in days. (Cohort 3 and 4)
Time frame: up to 2 years
K13 mutations
Rate of K13 mutation and Artemisinin partial resistance. (Cohort 3 and 4)
Time frame: up to 2 years
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)
Time frame: During treatment of malaria episodes over 2 years
Plan to share: Yes — Data will be de-identified, and shared on clinepidb.org upon conclusion of the study
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