By Michael Gwarisa
The U.S. Food and Drug Administration (FDA) has approved a new formulation of the HIV medicine dolutegravir for use in newborns from birth through four weeks of age, expanding treatment options for one of the most vulnerable groups at risk of HIV infection.
The approval covers Tivicay PD tablets for oral suspension for babies weighing at least 2 kilogrammes. The medicine is to be used in combination with other antiretroviral drugs.
Tivicay and Tivicay PD, both manufactured with the active ingredient dolutegravir, had previously been approved for adults and children older than four weeks.
The latest approval means dolutegravir can now be used from the first days of life in eligible newborns, an important development in efforts to prevent and treat HIV in infants.
HIV attacks the body’s immune system and, without treatment, can lead to acquired immunodeficiency syndrome (AIDS). Although there is currently no cure for HIV, antiretroviral therapy can suppress the virus and allow people living with HIV to live longer, healthier lives.
Evidence from newborn study
The FDA’s decision was supported by data from the IMPAACT 2023 study, together with pharmacokinetic modelling.
The Phase I study evaluated the safety, tolerability and pharmacokinetics of dolutegravir in newborns born to mothers living with HIV-1.
A total of 48 newborns who had been exposed to HIV-1 and weighed at least 2 kilogrammes were enrolled. The infants received Tivicay PD from birth for up to six weeks alongside standard antiretroviral medicines used to prevent mother-to-child transmission of HIV.
The infants were subsequently followed until 16 weeks of age.
The study found that dolutegravir concentrations in newborns were similar to levels associated with effectiveness in adults. The safety profile observed in the newborns was also consistent with what has been seen in older children and adults receiving the medicine.
The findings provided evidence to support the use of dolutegravir during the first weeks of life.
The IMPAACT 2023 study was conducted as a multicentre, open-label, non-comparative Phase I dose-finding study. It involved mother-infant pairs from Brazil, South Africa, Thailand and the United States.
The mothers did not receive the study drug and left the study after completing the initial assessment, while the infants were followed through 16 weeks of life.
Assessing dosing in the first weeks of life
Researchers examined how newborns absorbed, distributed and processed dolutegravir, with the aim of identifying a dosing regimen that would achieve appropriate drug levels while maintaining safety.
The study included infants whose mothers had and had not received dolutegravir close to delivery. This distinction was important because exposure to dolutegravir during pregnancy could affect the amount of medicine present in the newborn after birth.
The research used two dosing approaches.
In the first cohort, infants received two doses of dolutegravir approximately seven days apart. The second cohort received repeated dosing through four or six weeks of age, depending on the duration of standard antiretroviral prophylaxis used at the study site.
The study included both breastfed and formula-fed infants.
Researchers conducted detailed pharmacokinetic assessments after dosing, collecting blood samples at several points to determine how the drug behaved in the infants’ bodies.
Safety assessments included clinical examinations, laboratory tests and monitoring for adverse events, including serious events and deaths. Infants were followed through 16 weeks.
Safety considerations
The FDA said patients should not receive Tivicay or Tivicay PD if they have previously experienced an allergic reaction to dolutegravir or if they are taking dofetilide, a medicine used to treat certain heart rhythm problems.
Serious allergic reactions have been reported in people taking dolutegravir, and patients receiving the medicine should be monitored for signs of liver damage.
The FDA also noted that immune reconstitution syndrome has been reported in people receiving combination antiretroviral therapy. The condition can occur when the immune system begins to recover and responds strongly to infections that were previously present.
Caregivers and healthcare providers should also consider other medicines being taken by a newborn or child because some medicines can interact with dolutegravir. Such interactions can reduce the effectiveness of HIV treatment or increase the risk of side effects.
Importantly, Tivicay tablets and Tivicay PD tablets for oral suspension cannot be substituted for each other on a milligram-for-milligram basis.
Implications for infant HIV care
The approval comes against the backdrop of continued efforts to eliminate mother-to-child transmission of HIV.
Babies born to mothers living with HIV can be exposed to the virus during pregnancy, childbirth or breastfeeding. Providing effective antiretroviral medicines around the time of birth is therefore a critical component of preventing new infant HIV infections.
For newborns who acquire HIV despite prevention efforts, access to appropriate treatment from the earliest possible age is also essential.
Dolutegravir has become an important component of HIV treatment because of its potent antiviral activity and high barrier to resistance. Extending an appropriate formulation to newborns provides healthcare workers with another option during a period when medication dosing can be particularly challenging.
The Tivicay PD formulation is designed to be administered as an oral suspension, making it suitable for newborns who cannot swallow conventional tablets.
The FDA granted Tivicay PD priority review for this newborn population, reflecting the importance of making medicines available for serious conditions where treatment options may be limited.
The approval does not mean that every newborn exposed to HIV should automatically receive dolutegravir. Its use depends on the infant’s clinical circumstances, weight, HIV exposure or infection status, other antiretroviral medicines and applicable treatment or prevention guidelines.
Healthcare providers must determine the appropriate regimen and dosing for each infant.
