Optimizing malaria and HIV treatment for children in Busia and Kampala

OPTImizing Malaria And HIV Treatment in a Shifting Landscape in Africa

We will test whether dolutegravir affects growth and how it interacts with common malaria medicines in children with and without HIV, following them for two years in Busia and Kampala.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 380 (estimated)
• Ages: 5 Years to 17 Years
• Sex: All
• Sponsor: Yale University (Academic / other)
• Locations: 2 sites (Kampala and 1 other locations)
• Trial ID: NCT06967519 on ClinicalTrials.gov

What this trial studies

The project follows four parallel, age-matched cohorts of children — HIV-positive on dolutegravir and HIV-negative — at a high-transmission site (Busia) and a low-transmission site (Kampala) for two years. All children enroll malaria-free and are followed longitudinally for malaria episodes, clinical outcomes, body composition, and metabolic measures. In Busia, children are randomized to receive either artemether-lumefantrine or artesunate-amodiaquine for malaria episodes in year one, with one arm switching to alternating regimens in year two; treatment arms may be adjusted if national guidelines change. The study will link dolutegravir exposure, antimalarial pharmacokinetics, and markers of ACT resistance to clinical outcomes for both HIV and malaria.

Who should consider this trial

Good fit: Ideal candidates are children and adolescents who live within about 30 km of the Busia or Kampala study clinics, are malaria-negative at enrollment, and include both HIV-positive children on dolutegravir for at least 14 days and HIV-negative, age-matched peers.

Not a fit: Adults, children with major comorbidities (for example active TB, chronic hepatitis, severe malnutrition), those who are pregnant at enrollment, already have malaria at enrollment, or are taking medications that strongly interact with study drugs are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the results could guide safer and more effective choices of antimalarial treatment for children on dolutegravir and inform policies to reduce harmful drug interactions and resistance.

How similar studies have performed: Some prior studies have shown antiretroviral–antimalarial interactions and metabolic effects of dolutegravir, but comprehensive pediatric data combining DTG with common ACTs across different transmission settings are limited, so this approach is relatively novel.

Eligibility criteria

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

Where this trial is running

Kampala and 1 other locations

• Baylor- Uganda — Kampala, Uganda (Recruiting)
• Infectious Disease Research Collaboration (IDRC) — Kampala, Uganda (Recruiting)

Study contacts

• Principal investigator: Sunil Parikh, M.D., MPH — Yale School of Public Health
• Study coordinator: Sunil Parikh, MD, MPH

Conditions Malaria; Hiv