OPTImizing Malaria And HIV Treatment in a Shifting Landscape in Africa (OPTIMAH)

Yale University

Status and phase: Enrolling; Phase 4

Conditions: Malaria; Hiv

Treatments: Drug: artesunate-amodiaquine (AS-AQ); Drug: Artemether-lumefantrine (AL)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06967519

2R01HD068174-11A1 (U.S. NIH Grant/Contract)

2000039347

Details and patient eligibility

About

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.

Full 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

Enrollment: 380 estimated patients

Sex: All

Ages: 5 to 17 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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380 participants in 4 patient groups

CLHIV on DTG- Kampala (Cohort 1)

Experimental group

Description:

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

Treatment:

Drug: Artemether-lumefantrine (AL)

Drug: artesunate-amodiaquine (AS-AQ)

HIV-uninfected children- Kampala (Cohort 2)

No Intervention group

Description:

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

CLHIV on DTG- Busia (Cohort 3)

Experimental group

Description:

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

Treatment:

Drug: Artemether-lumefantrine (AL)

Drug: artesunate-amodiaquine (AS-AQ)

HIV-uninfected children- Busia (Cohort 4)

No Intervention group

Description:

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