Bictegravir, emtricitabine, and tenofovir alafenamide efficacy, safety in children with HIV 2 years and up

Bictegravir, emtricitabine, and tenofovir alafenamide efficacy, safety in children with HIV 2 years and up | Image Credit: © ronstik - © ronstik - stock.adobe.com.

Data from a open-label, multicenter, multicohort, single-arm study conducted in the United States, South Africa, Thailand, and Uganda, and published in The Lancet HIV, demonstrated support for the use of coformulated, low-dose single-tablet bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) to treat HIV in children weighing between 30.86 lbs (14 kg) and 55.11 lbs (25 kg).¹

Single-tablet, fixed-dose combinations (FDCs) of antiretroviral therapy (ART) have made management of HIV simpler, and have associations with improved adherence, particularly important in pediatric populations, noted study authors.¹

The low-dose tablet bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) has been approved in the United States for children weighing 30.86 lbs to less than 55.11 lbs, with it bringing a preferred regimen recommendation from the US Department of Health and Human Services.¹

The investigators aimed to evaluate safety, efficacy, and pharmacokinetics of the low-dose coformulated bictegravir, emtricitabine, and tenofovir alafenamide regimen in virologically suppressed children with HIV aged 2 years and older, who weigh between 30.86 lbs and 55.11 lbs.¹

The phase 2/3 study was conducted at 24 centers in the aforementioned countries, with the most studies conducted in the United States (n = 10). The current study included 3 cohorts. Cohort 1 included participants aged 12 years to younger than 18 years who weighed 35 kg or more. Cohort 2 featured participants aged 6 years to younger than 12 years who weighed 25 kg or more. Forty-eight-week results from these cohorts were previously published by The Lancet Child & Adolescent Health. Investigators concluded in the publication that the regimen was “well tolerated and maintained virological suppression. Our data support the treatment of HIV in adolescents and children with this single-tablet regimen.”^1,2

The current study population made up cohort 3, virologically suppressed children with HIV aged at least 2 years and within the specified weight range. Virological suppression was defined as “plasma HIV RNA of less than 50 copies per mL (or undetectable, if the limit of detection of the local assay used was ≥50 copies per mL) for at least 6 months before screening,” wrote the investigators.¹

Eligible participants in this cohort were receiving a stable ART regimen of 2 nucleoside reverse transcriptase inhibitors, plus a third agent for at least 6 months before screening. These participants also had adequate haematological function, CD4 cell counts of at least 200 cells per μL, normal liver function, as well as normal renal function.¹

Participants who completed the 48 weeks of study treatment were given the option to receive the regimen in an open-label extension phase.¹

Primary outcomes were steady-state pharmacokinetics for bictegravir at week 2, measured by area under the curve at the end of dosing interval (AUC_tau) and observed drug concentration of the end of dosing interval (C_tau), as well as the safety and tolerability of coformulated bictegravir, emtricitabine, and tenofovir alafenamide. This was measured by the incidence of adverse events and laboratory abnormalities on, or after the first bictegravir, emtricitabine, and tenofovir alafenamide dose until the last participant’s week 24 visit, according to the investigators.¹

Secondary endpoints included the proportion of participants with less than 50 copies of HIV RNA per mL at weeks 24 and 48, changes from baseline in CD4 cell count and percentage at weeks 24 and 48.¹

Twenty-two participants were screened, completed the single-tablet regimen until week 48, and entered an extension phase. The geometric least squares mean (GLSM) ration for AUC_tau for bictegravir was 7.6% higher than adults (GLSM ratio 107.6%, 90% CI 96.7 – 119.7). C_tau was lower than adults (65.4%, 49.1-87.2). Both parameters were within target exposure found in adults, children, or both. By the end of week 24, grade 3-4 laboratory abnormalities occurred in 4 (18%) of participants, and in 6 participants (27%) by the end of week 48.¹

Three participants (14%) experienced drug-related adverse events at the end of week 24 and week 48, of which none were severe. No grade 3-4 adverse events, serious adverse events, or adverse events leading to discontinuation occurred by the end of week 24 or week 48.¹

As a result, the study investigators concluded that data “support the use of single-tablet coformulated bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) for treatment of HIV in children aged at least 2 years and weighing 14 kg to less than 25 kg.”¹

References:

1. Rodriguez CA, Natukunda E, Strehlau R, et al. Pharmacokinetics and safety of coformulated bictegravir, emtricitabine, and tenofovir alafenamide in children aged 2 years and older with virologically suppressed HIV: a phase 2/3, open-label, single-arm study. The Lancet HIV. Published April 12, 2024. Accessed April 15, 2024. https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(23)00327-2/abstract#articleInformation
2. Gaur AH, Cotton MF, Rodriguez CA, et al. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide in adolescents and children with HIV: week 48 results of a single-arm, open-label, multicentre, phase 2/3 trial. The Lancet Child & Adolescent Health. Published July 21, 2021. Accessed April 15, 2024. https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(21)00165-6/abstract