Study Simplifies Dolutegravir Dosing for Children with HIV

A pharmacokinetic and safety substudy found that the 50 mg film-coated adult dose of dolutegravir given once daily is safe and effective for children with HIV weighing 20 kg or more.

An adult dose of dolutegravir (Tivicay) given once daily is safe and effective for children weighing 20 kg or more and could simplify speed up HIV treatment for children, according to a recent study.

The study, published in The Lancet HIV, examined 62 children ages 6 to 17 at 4 treatment centers in Uganda and Zimbabwe who were starting treatment for HIV in a pharmacokinetic and safety substudy within the multicenter, randomized ODYSSEY trial.

“The adult dolutegravir 50 mg filmcoated tablet given once daily provides adequate pharmacokinetic profiles in children weighing 20 kg or more with no safety signal of concern,” corresponding author Angela Colbers, PhD, department of pharmacy, Radboud Institute for Health Sciences, Netherlands, told Contagion®.

For children weighing 20 kg (44 lbs) to less than 25 kg (55 lbs) who are unable to swallow the adult tablets, an alternative dispersible tablet at a dose of 30 mg provided adequate pharmacokinetic profiles with no adverse safety signals.

The study also found that dolutegravir doses recommended by the European Medicines Authority for children weighing 20-40 kg (44-88 lbs) resulted in lower dolutegravir concentrations in the blood than expected. Those recommendations required 25 mg and 10 mg film-coated tablets, which aren’t readily available to low-resource areas.

“In HIV as well as in many other diseases in children, the drugs and the licensing of those drugs and the formulations often lag woefully behind adults,” study author Diana Gibb, MD, of the Medical Research Council Clinical Trials Unit at University College London, said in a conversation with The Lancet HIV.

About 1.7 million children under age 15 are living with HIV globally, with the vast majority in sub-Saharan Africa. In 2018, only about 56% of infected children had access to antiretroviral therapy.

“The advent of the integrase inhibitor class of drugs and dolutegravir in particular is really making a landmark change in the way that treatment might be given to adults and children because it can be well formulated into both adult formulations but also importantly into smaller children’s formulations,” Gibb said. “Ideally, we want scored, dispersible tablets and not too many formulations for children because that’s difficult for programs. The trial that we talked about in this paper nested a way of looking at minimizing formulations for children and getting the data we need for licensing and hopefully will make a big difference to the way children can access treatment for HIV.”

At the start of the trial, recommended treatments included 3 different formulations for childhood doses according to World Health Organized-recognized weight bands. The study found that 2 formulations were adequate to treat patients across all weight bands.

“For the new treatment regimen to have a good potential, it needs to be not just efficacious and safe but also practical to administer,” study author Anna Turkova, MD, of the Medical Research Council Clinical Trials Unit at University College London, said in The Lancet HIV conversation. “The pediatric market for antiretrovirals is small and fragmented, especially compared to the adult market. For the drug to be made available and accessible widely for children, we need a minimal number of formulations to be used across all weight bands.”

Earlier this year, the US Food and Drug Administration approved dolutegravir tablets and tablets for suspension (Tivicay PD) for the treatment of HIV-1 infection in pediatric patients as young as 4 weeks and as light as 3 kg (6.61 lbs).

ViiV Healthcare made regulatory submissions to both the FDA and the EMA late last year, seeking approval for the first 5 mg dispersible tablet formulation of the dolutegravir, as well as a dosing regimen to optimise the use of existing dolutegravir 50mg film coated tablets in pediatric HIV patients.

Research for the ODYSSEY trial is ongoing.

“We will provide dolutegravir dosing recommendations for younger children, and for children using rifampicin for tuberculosis treatment in combination with dolutegravir,” Colbers told Contagion®. “Furthermore, the results of the main Odyssey trial will be analyzed and made public, also including efficacy data of dolutegravir in children."