The antiretroviral dolutegravir (Tivicay PD, ViiV Healthcare) is now the first second-generation integrase strand transfer inhibitor (INSTI) available for use with other antiretroviral agents in newborns with HIV, following the FDA's August 26 approval of the drug for infants under 4 weeks old weighing at least 2 kg. 

"This is a welcome expansion of our treatment options for newborns with HIV," Carlos Oliveira, MD, PhD, a pediatric infectious diseases specialist at Yale Medicine and medical director of the Yale pediatric HIV/AIDS program, New Haven, Connecticut, told Medscape Medical News. While other effective antiretroviral therapy (ART) regimens existed that could be started at birth, the ability to now use dolutegravir from the first days of life is a particular advantage, he said, as it "is one of our preferred HIV medications for older children and adolescents because it is highly effective and generally well tolerated." 

Michelle C. Collins-Ogle, MD, a pediatric and adolescent HIV physician at Children's Hospital at Montefiore and associate professor of pediatrics at Montefiore Einstein, The Bronx, New York, agreed, telling Medscape that it's "it's exciting news that we have another option to treat newborns who are living with HIV." The last new HIV medication approved for babies was Triumeq — a combination of abacavir, dolutegravir, and lamivudine in dispersible tablets — but it was only approved aged 3 months and older in infants weighing at least 6 kg.

"This represents a meaningful step forward for care of newborns," Collins-Ogle said. As in most adults, newborns with HIV require a combination of three active antiretrovirals, she said. The current gold standard of treatment is a combination of sidovudine, lamivudine, and nevirapine. "As of today, newborns can be offered a more robust treatment regimen," she said.

Tivicay and Tivicay PD, manufactured by ViiV Healthcare, were already approved for adults and children aged 4 weeks and older, respectively, but fewer options existed for infants under 4 weeks. If not diagnosed and treated early, HIV progresses rapidly in infants, with about half those born with perinatal infections dying by age 2 and 80% dying before age 5. 

Risk for perinatal HIV transmission in the US was 0.9% in 2019, down from 1.6% in 2010. Though more recent data are sparse, an estimated 3915 women with HIV had live births in 2014, according to the CDC, with no more than 5000 likely giving birth annually in subsequent estimates. Fewer than 50 infants a year are diagnosed with HIV in the US each year, a number that has been declining with increased options and access for viral suppression during pregnancy in the past decade. 

The FDA priority review approval decision was based on the IMPAACT 2023 study, a phase 1, multi-center, open-label cohort trial funded by the National Institutes of Health that assessed the safety, tolerability, and pharmacokinetics of dolutegravir in children under 4 weeks old. In the trial, 48 newborns who weighed at least 2 kg received dolutegravir starting at birth and continuing for up to 6 weeks, along with standard-of-care ART, with follow-up through 16 weeks old. 

The results showed similar efficacy from Tivicay PD in newborns as that seen in adults, with a comparable safety profile. 

"Previous available regimens for treating newborns were more complicated to prepare and involve complex dosing schedules. Tivicay PD is easy to prepare and is well tolerated," Diana F. Clarke, PharmD, an assistant professor of pediatrics at Boston University School of Medicine and lead investigator of the IMPAACT 2023 study, told Medscape. "We can now offer these mothers hope that with more potent, safer drugs to treat HIV-1 infection starting at birth, the most effective therapies will result in the best possible outcomes for their infants." 

Parents were willing to have their children participate in the study even knowing that their babies may not necessarily receive direct benefit but that "information learned in this study could benefit other babies in the future," Clarke said, adding that very few participants withdrew consent or were lost to follow-up.

"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 pediatric patients," Clarke said.

"Dolutegravir also has a high barrier to resistance," Oliveira said. "That is particularly important in pediatric HIV care because children will need treatment throughout their lives, and preserving future treatment options is extremely important."

Based on the trial and pharmacokinetics data, the federal pediatric HIV guidelines had already been updated in June to make the preferred regimen in full-term infants under 1 month old with HIV infection to be a backbone of two nucleoside reverse transcriptase inhibitors plus dolutegravir. 

Dolutegravir's intended administration in infants is tablets for oral suspension, and it's contraindicated in patients taking dofetilide. 

"Integrase strand transfer inhibitors have been part of first-line therapy for adults, and now we can mirror this treatment standard with newborns," Collins-Ogle said. "With a disbursable tab formulation, it's easy to administer to newborns and babies."

Despite having a better treatment option now, "more work is still needed to provide parents a single combination formulation for their infants, like those already available for older children and adults," Oliveira said. 

"Babies can rapidly progress to AIDS, even with current treatments, and this new option will be meaningful," Collins-Ogle said. "We are hopeful that this more effective treatment can minimize the burden of HIV, improve viral suppression and lead to better clinical outcomes." 

Collins-Ogle is in the process of beginning a study with Merck for use of doravirine/islatravir in pediatric and adolescent patients with HIV. Oliveira had no disclosures. The IMPAACT 2023 study was a collaboration between ViiV Healthcare/GSK and the IMPAACT network funded by the National Institutes of Health. 

Tara Haelle is a science/health journalist based in Dallas.