OPTImizing Malaria And HIV Treatment in a Shifting Landscape in Africa

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

380 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-31

Study Completion Date

2027-12-31

Brief Summary

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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.

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Detailed Description

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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

Conditions

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Malaria Hiv

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CLHIV on DTG- Kampala (Cohort 1)

CLHIV on DTG living in the low transmission malaria setting of Kampala

Group Type EXPERIMENTAL

Artemether-lumefantrine (AL)

Intervention Type DRUG

Participants will receive the dispersible formulation of AL with contains 20 mg artemether, 120 mg of lumefantrine

artesunate-amodiaquine (AS-AQ)

Intervention Type DRUG

Children will receive the tablet formulations of Artesunate Amodiaquine using weight based dosing

HIV-uninfected children- Kampala (Cohort 2)

HIV-uninfected children living in the low malaria transmission site of Kampala (control)

Group Type NO_INTERVENTION

No interventions assigned to this group

CLHIV on DTG- Busia (Cohort 3)

CLHIV on DTG living in the high malaria transmission site of Busia

Group Type EXPERIMENTAL

Artemether-lumefantrine (AL)

Intervention Type DRUG

Participants will receive the dispersible formulation of AL with contains 20 mg artemether, 120 mg of lumefantrine

artesunate-amodiaquine (AS-AQ)

Intervention Type DRUG

Children will receive the tablet formulations of Artesunate Amodiaquine using weight based dosing

HIV-uninfected children- Busia (Cohort 4)

HIV-uninfected children living in high malaria transmission site of Busia (control)

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Artemether-lumefantrine (AL)

Participants will receive the dispersible formulation of AL with contains 20 mg artemether, 120 mg of lumefantrine

Intervention Type DRUG

artesunate-amodiaquine (AS-AQ)

Children will receive the tablet formulations of Artesunate Amodiaquine using weight based dosing

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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

Minimum Eligible Age

5 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes