Dolutegravir from birth: Q&A with IMPAACT 2023 lead investigator

The FDA has approved dolutegravir (Tivicay PD; ViiV Healthcare) for the treatment of HIV-1 in children weighing at least 2 kg, including eligible newborns, making it the first second-generation integrase strand transfer inhibitor (INSTI) approved for this population. The approval, announced August 26, 2026, after Priority Review, covers use in combination with other antiretroviral agents in pediatric patients who are treatment-naïve or who are treatment-experienced but INSTI-naïve.¹

The decision was supported by the National Institutes of Health-funded IMPAACT 2023 study and by pharmacokinetic modeling that incorporated additional pediatric data. Together, these data showed that dolutegravir reached therapeutic levels in term neonates, with a safety profile consistent with that seen in older pediatric and adult populations. The need for effective options early in life is significant: without early diagnosis and treatment, HIV can progress rapidly in infants, and about 50% of untreated infants with HIV die by age 2 years, according to UNICEF and UNAIDS figures cited by the company.¹

Contemporary Pediatrics spoke with Diana F. Clarke, PharmD, assistant professor of pediatrics at Boston University School of Medicine and lead investigator of IMPAACT 2023, about what the study showed, how modeling was used to set the newborn dosing regimen, practical considerations for pediatricians initiating therapy, and the questions that remain for preterm infants.²

This interview has been edited for length and clarity.

Contemporary Pediatrics: What did the IMPAACT 2023 study show about the pharmacokinetics and safety of dolutegravir in term newborns, and which findings were most important in supporting its use beginning at birth?

Clarke: The pharmacokinetic and safety results from IMPAACT 2023 support the use of dolutegravir from birth in full-term neonates. Dolutegravir plasma concentrations achieved using the approved dosing regimen are consistent with those associated with virologic efficacy in older infants, children, and adults, and were shown to have a similar safety profile as those observed in older patients.

The pharmacokinetic findings are consistent with our understanding of drug metabolism and elimination in infants. Drug elimination immediately after birth is typically slow and increases rapidly over the first few weeks and months of life. As a result, drugs need to be well studied in newborns before they can be safely used in this vulnerable population.

Contemporary Pediatrics: Why is having a dolutegravir-based regimen available from birth significant for infants with HIV, particularly given the importance of achieving viral suppression early in life?

Clarke: Dolutegravir is a preferred antiretroviral agent for use in combination with other drugs for the treatment of HIV-1 infection in pediatric and adult patients. Dolutegravir is a second-generation integrase strand transfer inhibitor (INSTI) with a high genetic barrier to resistance that has potent antiviral activity, is highly effective, and is well tolerated. Being able to initiate therapy with dolutegravir starting at birth will greatly simplify therapy and allow for the use of the most effective antiretroviral drugs available at this time for use in infants. We can now offer parents and caregivers the option to start potent, safer drugs at birth to control the virus and protect the immune system. This represents an important advance for the care of newborns, as early treatment with the most effective therapies results in the best possible outcomes.

Dolutegravir is available as a well-tolerated dispersible tablet that is easy to prepare and suitable for use in neonates. Generic dolutegravir dispersible tablets for pediatric patients are available for use in resource-limited settings. The results from IMPAACT 2023 and the PETITE-DTG study conducted in South Africa were used to support the most recent WHO HIV Dosing Guidelines for Prevention and Treatment in Paediatric Populations. DTG is now included as an option for term neonates with birthweight ≥2 kg.

Contemporary Pediatrics: The FDA approval was supported by IMPAACT 2023 data as well as pharmacokinetic modeling. How was modeling used to establish the dosing regimen for newborns, and how confident can clinicians be that these exposures are comparable with those seen in older children?

Clarke: An innovative, adaptive, model-informed design involving two cohorts of participants was used to facilitate conduct of the IMPAACT 2023 study. Pharmacokinetic (PK) modeling and simulations using initial dolutegravir drug concentrations observed from single dolutegravir doses administered to a small group of newborns enrolled in Cohort 1 were combined with PK data from older infants and children. This adaptive design allowed the protocol team to select an initial dose to study for chronic administration in newborns enrolled in Cohort 2 without exposing any newborns to potentially dangerous high dolutegravir plasma concentrations. Ongoing review of PK and safety results by the protocol team occurred in real time as data became available to ensure that PK targets were achieved and no unexpected toxicities occurred.

Contemporary Pediatrics: For pediatricians caring for newborns with HIV, what practical considerations should they keep in mind when initiating Tivicay PD, including dosing, administration, drug interactions, and monitoring for adverse events?

Clarke: Dolutegravir is limited to use in term infants (≥37 weeks of gestation and weight ≥2 kg) or preterm infants with a postmenstrual age ≥37 weeks at the time of treatment initiation. Every other day dosing during the first 2 weeks of life may be challenging for some caregivers. Additional education and/or dosing calendars, telephone reminders, or other adherence tools may be helpful to ensure that the medication is being properly administered.

Contemporary Pediatrics: Now that dolutegravir is available for eligible newborns weighing at least 2 kg, what unanswered questions remain about its use in the youngest patients, and what additional long-term safety or efficacy data would you like to see?

Clarke: The chronic dosing regimen evaluated in IMPAACT 2023 is not recommended for preterm infants. Preterm neonates have impaired bilirubin-albumin binding, lower UGT1A1 activity, and greater physiologic variability in drug clearance, increasing susceptibility to bilirubin-induced neurologic dysfunction from drug displacement interactions with drug accumulation. Because clinical assays to measure unbound unconjugated bilirubin are not available, accurately assessing bilirubin toxicity is not possible in preterm infants when integrase inhibitors are administered in this population. Safe and effective use of dolutegravir in preterm infants will require careful evaluation of pharmacokinetic and safety data from dedicated studies in preterm infants.

References

ViiV Healthcare. Helping close a critical HIV treatment gap. Press release. ViiV 1. Healthcare. Published August 26, 2026. Accessed October 7, 2026. https://viivhealthcare.com/en-us/media-center/news/press-releases/2026/august/helping-close-a-critical-hiv-treatment-gap/

2. Clarke DF. Interview with Contemporary Pediatrics on dolutegravir and the IMPAACT 2023 study. Published October 8, 2026.