A Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Dolutegravir in Neonates Exposed to HIV-1
Rationale
New antiretroviral drugs (ARVs) are crucial for neonatal use, serving both as HIV transmission prophylaxis and treatment for newborns with HIV. Dolutegravir, a potent ARV with a robust resistance barrier, is widely employed across age groups but not in newborns due to formulation challenges. While the DTG DT formulation is simpler, it’s limited in delivering doses under 5 mg accurately. To address this, a DTG liquid suspension was developed for the IMPAACT 2023 PK study, offering flexibility in dosing.
Before DTG can be applied in neonates, its safety and pharmacokinetics (PK) in this group must be studied thoroughly to propose a safe dosage. This study aims to provide PK and initial safety data to establish a recommended neonatal DTG dose using either the DTG DT formulation or the liquid suspension. Data from Cohort 1 will guide dosing strategies for chronic use in Cohort 2, potentially highlighting weight-related considerations for the DTG DT.
Commercialization of the study products hinges on the gathered data. The liquid formulation is designed to be commercialized if deemed necessary, ensuring availability for neonates if the DTG DT is unsuitable. Depending on the study’s outcomes, either the DT or the liquid formulation, or both, could be indicated for HIV-1 treatment in neonates alongside other ARV agents.
Dolutegravir will complement the standard care regimen for newborns in HIV prevention or treatment. This study’s design aligns with previous studies examining ARV PK and safety in neonates, ensuring careful PK sampling and follow-up in line with standard ARV prophylaxis guidelines.
Cohort 1 infants will receive single DTG doses to inform dosing strategies for Cohort 2, with specific protocols for DTG-naïve and DTG-exposed infants. Maternal data will guide ARV regimens and assess perinatal transmission risks. Cohort 2 will receive chronic DTG doses based on PK analyses, either with the DTG DT formulation or the liquid suspension.
This study aims to establish safe and effective DTG dosing in neonates, contributing significantly to HIV management in this vulnerable population.
Investigators
- Dr Muneerah Khan
- Dr Mrinmayee Dhar
- Prof Lee Fairlie
- Dr Faeezah Patel
- Dr Elizea Horn
- Dr Pemphero Chisela
- Lucky Mondlane
- Othusitse Segalo
- Tiffany Seef
Latest Update
April 2024
For more about IMPAACT 2023 please email rhicomms@wrhi.ac.za
