OPTImizing Malaria And HIV Treatment in a Shifting Landscape in Africa

NCT06967519 | Recruiting Phase 4

• 2 other identifiers: 20000393472R01HD068174-11A1
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Malaria; Hiv

Outcome Measures

Primary Outcomes (4)

• Change in Body Mass Index (BMI)

  Change in BMI from baseline and 2 years in kg/m² (Cohort 1 + 3 vs Cohort 2 + 4)

  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)

  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)

  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.

  28 days and 42 days

Secondary Outcomes (11)

• Average change in glucose sensor readings

  every 6 months up to 2 years

• Change in insulin resistance (HOMA-IR)

  baseline and 2 years

• Change in Body Mass Index (BMI)

  baseline and 2 years

• Pharmacokinetic parameters

  immediately post drug exposure (Day 1)

• Change in HIV viral load

  every 6 months up to 2 years

Other Outcomes (3)

• Time to resistance

  up to 2 years

• K13 mutations

  up to 2 years

• Prevalence of mutations in malaria transporters

  During treatment of malaria episodes over 2 years

Study Arms (4)

CLHIV on DTG- Kampala (Cohort 1)

EXPERIMENTAL

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

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

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)

Interventions

Artemether-lumefantrine (AL) DRUG

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

CLHIV on DTG- Busia (Cohort 3); CLHIV on DTG- Kampala (Cohort 1)

artesunate-amodiaquine (AS-AQ) DRUG

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

CLHIV on DTG- Busia (Cohort 3); CLHIV on DTG- Kampala (Cohort 1)

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

Baylor- Uganda

Kampala, Uganda

RECRUITING

Infectious Disease Research Collaboration (IDRC)

Kampala, Uganda

RECRUITING

MeSH Terms

Conditions

Malaria; Acquired Immunodeficiency Syndrome

Interventions

Artemether, Lumefantrine Drug Combination; amodiaquine, artesunate drug combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Sunil Parikh, M.D., MPH

  Yale School of Public Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sunil Parikh, MD, MPH

CONTACT

1-203-737-7906; sunil.parikh@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 23, 2025
• First Posted: May 13, 2025
• Study Start: December 18, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

UG (2)