OPTImizing Malaria And HIV Treatment in a Shifting Landscape in Africa

Обзор

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.

Подробное описание

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

Вмешательства

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

Первичные конечные точки

• Change in Body Mass Index (BMI) [Срок оценки: baseline and 2 years]
• Drug pharmacokinetic (PK) exposure [Срок оценки: baseline up to 2 years]
• Drug pharmacokinetic exposure [Срок оценки: baseline up to 2 years]
• Recurrence rate of malaria [Срок оценки: 28 days and 42 days]

Вторичные конечные точки (11)

• Average change in glucose sensor readings [Срок оценки: every 6 months up to 2 years]
• Change in insulin resistance (HOMA-IR) [Срок оценки: baseline and 2 years]
• Change in Body Mass Index (BMI) [Срок оценки: baseline and 2 years]
• Pharmacokinetic parameters [Срок оценки: immediately post drug exposure (Day 1)]
• Change in HIV viral load [Срок оценки: every 6 months up to 2 years]
• Malaria treatment outcome [Срок оценки: 28 days and 42 days]
• HIV genotypic resistance to DTG [Срок оценки: baseline and 2 years]
• Artemisinin PK concentration-time profile [Срок оценки: During treatment of malaria episodes over 2 years]
• Rate of parasite clearance [Срок оценки: During treatment of malaria episodes over 2 years]
• Rate of parasite clearance and HIV [Срок оценки: During treatment of malaria episodes over 2 years]
• Gametocyte quantity [Срок оценки: At the time of presentation with malaria up to 2 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Uganda · 2 центра

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

Идентификаторы

NCT: NCT06967519 · 2000039347 · 2R01HD068174-11A1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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