OPTImizing Malaria And HIV Treatment in a Shifting Landscape in Africa

Phase 4RecruitingNCT06967519

Yale University380 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Malaria Hiv

Interventions

Artemether-lumefantrine (AL)DRUG

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

artesunate-amodiaquine (AS-AQ)DRUG

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

Eligibility

Sex: ALLMin age: 5 YearsMax age: 17 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (2)

Baylor- Uganda

Kampala, Uganda

RECRUITING

Infectious Disease Research Collaboration (IDRC)

Kampala, Uganda

RECRUITING

Outcomes

Primary Outcomes

Change in Body Mass Index (BMI)

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

Time frame: 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)

Time frame: 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)

Time frame: 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.

Time frame: 28 days and 42 days

Secondary Outcomes

Average change in glucose sensor readings

Change in average of continuous glucose monitor readings over the last 10 days. (Cohorts 1 vs 2)

Time frame: every 6 months up to 2 years

Change in insulin resistance (HOMA-IR)

Change in HOMA-IR in those living with and without HIV. (Cohorts 1+3 vs 2+4)

Time frame: baseline and 2 years

Change in Body Mass Index (BMI)

Change in BMI in children living with HIV from baseline and 2 years in kg/m² (Cohort 1 vs 3)

Time frame: baseline and 2 years

Pharmacokinetic parameters

Central Contacts

Sunil Parikh, MD, MPH

CONTACT

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

Data from ClinicalTrials.gov

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