NCT06967519

OPTImizing Malaria And HIV Treatment in a Shifting Landscape in Africa

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 380 (estimated)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 5 Years – 17 Years
• Healthy volunteers: Accepted

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). 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

Conditions

• Malaria
• Hiv

Interventions

Type	Name	Description
DRUG	Artemether-lumefantrine (AL)	Participants will receive the dispersible formulation of AL with contains 20 mg artemether, 120 mg of lumefantrine
DRUG	artesunate-amodiaquine (AS-AQ)	Children will receive the tablet formulations of Artesunate Amodiaquine using weight based dosing

Timeline

• Start date: 2025-12-18
• Primary completion: 2027-12-01
• Completion: 2027-12-01
• First posted: 2025-05-13
• Last updated: 2026-02-04

Locations

2 sites across 1 country: Uganda