# Optimizing ACT use for African children in the setting of HIV and malnutrition

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $540,524

## Abstract

Project Abstract
Although the artemisinin-combination therapies (ACTs) are the most important drugs for the
treatment of uncomplicated malaria, fundamental questions are unanswered including which
ACT choice and dose is best for HIV-infected and HIV-uninfected children. In our first funding
cycle we focused on artemether-lumefantrine as the most commonly prescribed ACT in Uganda
and generated striking results that showed the pharmacokinetic (PK) exposure of lumefantrine,
the compound most important for preventing new infections, can range by 10-fold depending on
which HIV antiretroviral (ART) an HIV-infected child is receiving. Likewise, the artemisinins were
also impacted, with efavirenz-based ART dramatically reducing both the artemisinins and
lumefantrine. The contrasting effects seen with various ART led to significant differences in
malaria clinical outcomes. Moreover, we studied HIV-uninfected children and learned that
underweight children are also susceptible to important PK and pharmacodynamic (PD,
exposure-response) distinctions. For our renewal we will focus on three aims. First we will
determine the PK/PD of an extended artemether-lumefantrine dosing regimen in HIV-infected
children on efavirenz-based ART that is designed to improve the PK exposure and treatment
efficacy of this ACT regimen. Second, we will extend our studies to investigate, for the first time,
the PK of another first line ACT, dihydroartemisinin-piperaquine, in HIV-infected children, who
are on first-line ART. Third, we will determine the impact of specific classifications of
malnutrition on the PK/PD of artemether-lumefantrine and dihydroartemisinin-piperaquine in
HIV-uninfected young children and directly compare children who are underweight or stunted
(the two most common forms of malnutrition in Uganda) to children with normal growth indices.
Our overarching goal continues to be to inform the best treatment guidelines for young children
in Africa. HIV-infected and HIV-uninfected children will be enrolled for intensive PK studies, as
well as additional children for population PK studies to enhance association analyses with
clinical outcomes. As for our first funding cycle, this proposal will leverage the outstanding
infrastructure available in Tororo, Uganda and will benefit from the highly complementary
expertise of Drs. Aweeka and Parikh who will continue to serve as joint-PIs.

## Key facts

- **NIH application ID:** 10001360
- **Project number:** 5R01HD068174-10
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** FRANCESCA T. AWEEKA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $540,524
- **Award type:** 5
- **Project period:** 2010-12-23 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001360

## Citation

> US National Institutes of Health, RePORTER application 10001360, Optimizing ACT use for African children in the setting of HIV and malnutrition (5R01HD068174-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001360. Licensed CC0.

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