MalariaPhase 4OPTIMAHNCT06967519
OPTImizing Malaria And HIV Treatment in a Shifting Landscape in Africa
A Phase 4 study testing Artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ) in people with Malaria and Hiv, run by Yale University at 2 sites in Uganda.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 5 to 17 yearsHealthy volunteers can take part
- What is being tested?
- Artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 380 participants
- Where
- 2 sitesUganda
- Study dates
- 18 Dec 2025to Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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)
- For Children and adolescents living with HIV
- Confirmed HIV infection
- On DTG-based regimen for ≥14 days
- For HIV-uninfected children - documentation of HIV-negative status by at least 1 assay
Who cannot join
- 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
- Prior intolerance to AL or AS-AQ (for those in Busia only)
- Pregnancy at enrolment (testing done at enrollment for all those of child-bearing age)
- Concurrent enrolment in another research study
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Uganda2 sites, 2 recruiting
- Recruiting
Baylor- Uganda
Kampala
Peter J Elyanu, MD, PhD
- Recruiting
Infectious Disease Research Collaboration (IDRC)
Kampala
Norah Mwebaza, DPPM, PhD
About this study
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.
Read the detailed description
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)
- Fever (≥ 37.5ºC axillary) or history of fever in the previous 24 hours
- Positive thick blood smear (any parasitemia)
- Absence of severe malaria Severe malaria
- Evidence of severe malaria as per WHO criteria
- Being tested
- Artemether-lumefantrine (AL), artesunate-amodiaquine (AS-AQ)
- Medical subject headings
- Malaria, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemether-lumefantrine (AL)Drug
Participants will receive the dispersible formulation of AL with contains 20 mg artemether, 120 mg of lumefantrine
artesunate-amodiaquine (AS-AQ)Drug
Children will receive the tablet formulations of Artesunate Amodiaquine using weight based dosing
| Study group | Role | What they receive |
|---|---|---|
| CLHIV on DTG- Kampala (Cohort 1) | Experimental | CLHIV on DTG living in the low transmission malaria setting of Kampala Receives: Drug: Artemether-lumefantrine (AL); Drug: artesunate-amodiaquine (AS-AQ) |
| HIV-uninfected children- Kampala (Cohort 2) | No intervention | HIV-uninfected children living in the low malaria transmission site of Kampala (control) |
| CLHIV on DTG- Busia (Cohort 3) | Experimental | CLHIV on DTG living in the high malaria transmission site of Busia Receives: Drug: Artemether-lumefantrine (AL); Drug: artesunate-amodiaquine (AS-AQ) |
| HIV-uninfected children- Busia (Cohort 4) | No intervention | HIV-uninfected children living in high malaria transmission site of Busia (control) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Body Mass Index (BMI)
Change in BMI from baseline and 2 years in kg/m² (Cohort 1 + 3 vs Cohort 2 + 4)
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 28 days and 42 days
Secondary outcomes (11)
Average change in glucose sensor readings
Change in average of continuous glucose monitor readings over the last 10 days. (Cohorts 1 vs 2)
Measured: 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)
Measured: 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)
Measured: baseline and 2 years
Pharmacokinetic parameters
AUC (0-8h) and AUC (last) for lumefantrine and DEAQ. (Cohorts 1 and 3)
Measured: 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)
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: At the time of presentation with malaria up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2025
- Study start18 Dec 2025
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Only Busia participants (HIV-infected and HIV-uninfected, Cohorts 3 and 4) 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 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..). CLHIV, ages 5-17 years, will be identified from respective registers at Baylor-Uganda (in Kampala) and the Masafu HIV clinic (and nearby clinics) in Busia Uganda. HIV-uninfected children, also ages 5-17 years, will be enrolled from catchment areas at these two sites. Recruitment will be balanced by age and sex.
- Masking
- None (open label)
- Enrolment
- 380 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Sunil Parikh, M.D., MPH, Principal investigator, Yale School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06967519
- Sponsor's protocol ID
- 2000039347
- Other IDs
- 2R01HD068174-11A1
- Acronym
- OPTIMAH
- Status last verified
- Feb 2026
- First submitted
- 23 Apr 2025
- Last updated
- 4 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be de-identified, and shared on clinepidb.org upon conclusion of the study
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- OPTImizing Malaria And HIV Treatment in a Shifting Landscape in Africa
- ClinicalTrials.gov ID
- NCT06967519
- Acronym / sponsor ID
- OPTIMAH / 2000039347
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 380 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 18 Dec 2025 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 13 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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)
- Fever (≥ 37.5ºC axillary) or history of fever in the previous 24 hours
- Positive thick blood smear (any parasitemia)
- Absence of severe malaria Severe malaria
- Evidence of severe malaria as per WHO criteria
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Only Busia participants (HIV-infected and HIV-uninfected, Cohorts 3 and 4) 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 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..). CLHIV, ages 5-17 years, will be identified from respective registers at Baylor-Uganda (in Kampala) and the Masafu HIV clinic (and nearby clinics) in Busia Uganda. HIV-uninfected children, also ages 5-17 years, will be enrolled from catchment areas at these two sites. Recruitment will be balanced by age and sex.
| Arm | Type | Receives |
|---|---|---|
| CLHIV on DTG- Kampala (Cohort 1) | Experimental | Drug: Artemether-lumefantrine (AL), Drug: artesunate-amodiaquine (AS-AQ)CLHIV on DTG living in the low transmission malaria setting of Kampala |
| HIV-uninfected children- Kampala (Cohort 2) | No intervention | –HIV-uninfected children living in the low malaria transmission site of Kampala (control) |
| CLHIV on DTG- Busia (Cohort 3) | Experimental | Drug: Artemether-lumefantrine (AL), Drug: artesunate-amodiaquine (AS-AQ)CLHIV on DTG living in the high malaria transmission site of Busia |
| HIV-uninfected children- Busia (Cohort 4) | No intervention | –HIV-uninfected children living in high malaria transmission site of Busia (control) |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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)
- For Children and adolescents living with HIV
Key exclusion criteria (7 listed)
- 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
- Prior intolerance to AL or AS-AQ (for those in Busia only)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Artemether-lumefantrine (AL)Participants will receive the dispersible formulation of AL with contains 20 mg artemether, 120 mg of lumefantrine | Drug | CLHIV on DTG- Busia (Cohort 3), CLHIV on DTG- Kampala (Cohort 1) |
| artesunate-amodiaquine (AS-AQ)Children will receive the tablet formulations of Artesunate Amodiaquine using weight based dosing | Drug | CLHIV on DTG- Busia (Cohort 3), CLHIV on DTG- Kampala (Cohort 1) |
Primary outcome
Change in Body Mass Index (BMI)
Time frame: baseline and 2 years
Change in BMI from baseline and 2 years in kg/m² (Cohort 1 + 3 vs Cohort 2 + 4)
Drug pharmacokinetic (PK) exposure
Time frame: baseline up to 2 years
Comparison of drug exposure by DTG and anti-malarial regimen using Area under the curve (AUC) (Cohort 1 vs 3)
Drug pharmacokinetic exposure
Time frame: baseline up to 2 years
Comparison of drug exposure by DTG and anti-malarial regimen using Area under the curve (AUC) (Cohort 3 vs 4)
Recurrence rate of malaria
Time frame: 28 days and 42 days
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.
11 secondary outcomes
Average change in glucose sensor readings
Time frame: every 6 months up to 2 years
Change in insulin resistance (HOMA-IR)
Time frame: baseline and 2 years
Change in Body Mass Index (BMI)
Time frame: baseline and 2 years
Pharmacokinetic parameters
Time frame: immediately post drug exposure (Day 1)
Change in HIV viral load
Time frame: every 6 months up to 2 years
Malaria treatment outcome
Time frame: 28 days and 42 days
HIV genotypic resistance to DTG
Time frame: baseline and 2 years
Artemisinin PK concentration-time profile
Time frame: During treatment of malaria episodes over 2 years
Rate of parasite clearance
Time frame: During treatment of malaria episodes over 2 years
Rate of parasite clearance and HIV
Time frame: During treatment of malaria episodes over 2 years
Gametocyte quantity
Time frame: At the time of presentation with malaria up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2026.
- Individual participant dataSharing planned: Yes. Data will be de-identified, and shared on clinepidb.org upon conclusion of the study
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sunil Parikh, M.D., MPH principal investigator
Yale School of Public Health
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ) in people with Malaria and Hiv, run by Yale University at 2 sites in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sunil Parikh, MD, MPH (1-203-737-7906, sunil.parikh@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Body Mass Index (BMI) (time frame: baseline and 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2026.