The FDA has approved dolutegravir (Tivicay PD; ViiV Healthcare) tablets for oral suspension to treat HIV infection in newborns from birth to younger than 4 weeks who weigh at least 2 kg, when used with other antiretroviral agents. The approval expands the age range for the drug, which was previously limited to patients aged 4 weeks and older. This addition moves treatment into the first weeks of life, a period where age-appropriate options have historically been limited.
Newborn Dosing Based on Clinical Study
The decision follows findings from the phase 1 IMPAACT 2023 study (NCT05406583), a multicenter, open-label, noncomparative dose-finding study evaluating the safety, tolerability, and pharmacokinetics of dolutegravir in full-term newborns exposed to HIV-1. The study aimed to identify a neonatal dosing regimen that achieves pharmacokinetic exposures associated with effective use in older populations. According to the FDA, 48 newborns weighing at least 2 kg received dolutegravir beginning at birth and continuing for up to 6 weeks in addition to standard-of-care antiretroviral medications used to prevent mother-to-child HIV transmission. The infants were followed through 16 weeks of age.
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Dolutegravir concentrations observed in the newborns were comparable with drug exposures associated with efficacy in adults. The safety profile reported in newborns was similar to that previously observed in older pediatric patients and adults. The study data was supplemented by pharmacokinetic modeling and additional pediatric data to support the indication.
While the new formulation provides a treatment option for very young infants, the transition to adult dosing schedules is often complex. The agency notes that the drug is a second-generation integrase strand transfer inhibitor that blocks the strand-transfer step required for integration of viral DNA into host cells. Before the expanded approval, use of dolutegravir in the United States began at 4 weeks of age. ViiV Healthcare noted during regulatory review that approval for newborns would make dolutegravir the first second-generation integrase inhibitor available for this age group.
Guidance and Formulation Considerations
The National Institutes of Health (NIH) pediatric HIV guidance published before the FDA action had already incorporated neonatal dolutegravir based on the emerging pharmacokinetic data. The guidelines recommend dolutegravir with zidovudine plus either lamivudine or emtricitabine as a preferred initial regimen for full-term infants with HIV who weigh at least 2 kg. NIH guidelines describe the agent as a preferred integrase inhibitor that can be initiated at birth in eligible infants and continued as children grow, although dosing changes according to age and weight. Contemporary pediatric HIV guidance emphasizes initiating antiretroviral therapy promptly after diagnosis and recommends multidrug therapy for infants and children starting treatment.
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Pharmacists should note that the drug is supplied as tablets for oral suspension and should not be treated as interchangeable with conventional Tivicay tablets on a milligram-per-milligram basis. This distinction is particularly relevant during transitions between pediatric formulations or when medication histories are reconciled across inpatient and outpatient settings. The expanded indication places additional emphasis on accurate preparation and administration of the pediatric formulation.
Clinicians and pharmacists should also review concomitant medications because drug interactions can alter dolutegravir exposure or increase the risk of adverse effects. The drug is contraindicated in patients with a previous hypersensitivity reaction to the drug and in patients receiving dofetilide. Serious hypersensitivity reactions and hepatic adverse events have been reported, and immune reconstitution syndrome can occur after combination antiretroviral therapy is initiated.
