Use of SYMTUZA in Pediatric Patients

SUMMARY

• SYMTUZA is a complete regimen for the treatment of HIV-1 infected adults and adolescents aged 12 years and older with body weight at least 40 kg who are treatment-naïve or treatment-experienced with no darunavir (DRV) resistance-associated mutations (RAMs).¹
  • In adolescent patients aged 12 years and older weighing at least 40 kg, the recommended dosage is one tablet taken once daily (QD) with food.¹
  • No dose has been established for pediatric patients 3-11 years of age or weighing less than 40 kg.¹
  • SYMTUZA should not be used in pediatric patients below 3 years of age due to toxicity observed in juvenile rats dosed with darunavir (from 20 mg/kg-1000 mg/kg) up to days 23-26 of age.¹
• The pharmacokinetics (PK) of SYMTUZA in pediatric patients have not been investigated.
  • However, available PK data for the components of SYMTUZA indicate that there were no clinically relevant differences in exposure between adults and adolescents weighing at least 40 kg.
• The safety and efficacy of SYMTUZA in pediatric patients has not been investigated; however, the use of the components of SYMTUZA in adolescent patients aged 12-<18 years of age and weighing at least 40 kg is supported by 3 open-label clinical studies in HIV-1 infected pediatric patients.¹ Data from these studies showed that the overall safety profile in adolescents was similar to that observed in the adult population.
  • TMC114-C230 (DRV boosted with ritonavir [RTV]; n=12)
    • Please refer to the local DRV prescribing information for more information on this study.
  • GS-US-216-0128 (DRV boosted with cobicistat [COBI]; n=7)
    • Available data from this study are summarized below.²
    • Please contact Gilead Sciences for more information on this study.
  • GS-US-292-0106 (elvitegravir, cobicistat, emtricitabine [FTC], and tenofovir alafenamide [TAF]; n=50)
    • Please contact Gilead Sciences for more information on this study.
• A phase 1, single-dose study in adolescents found that 93% (25/27) of patients rated SYMTUZA as easy to swallow.³
• In a retrospective study evaluating the tolerability and efficacy of DRV/COBI in 15 children, DRV/COBI + 2 nucleoside reverse transcriptase inhibitors (NRTIs) maintained viral suppression in those suppressed at the time of switch; however, 8/15 patients discontinued therapy due primarily to tolerance or adherence issues.⁴

data with SYMTUZA

Crauwels et al (2018)³ evaluated the acceptability and swallowability of 2 placebo formulations equal in size and matching the fixed-dose combination products SYMTUZA (size, 22 mm X 10 mm) and DRV/COBI (size, 23 mm X 11.5 mm).

Study Design/Methods

• Phase 1, open-label, randomized, single-dose, crossover study that enrolled 27 HIV-1 infected adolescents 12 to <18 years old who weighed ≥40 kg.
  • Patients were stratified based on age: 12 to <15 years and 15 to <18 years.
  • Patients were virologically suppressed and had been on stable antiretroviral therapy for ≥3 months.
  • Patients’ ability and willingness to swallow a DRV 800 mg placebo tablet was assessed in the screening phase.
• On day 1, patients were randomly assigned to receive SYMTUZA placebo tablets (N=12) or DRV/COBI placebo tablets (N=15). At least 30 minutes later, they received the opposite regimen.
• A 7-point swallowability questionnaire and a 3-point acceptability questionnaire were completed by each patient following administration of the placebo tablets.
• The SYMTUZA data are presented below.

Results

• The median age was 14 years (range, 12 to 17), 52% of patients were male, the median body mass index was 21.1 kg/m², and 78% were currently taking a fixed-dose combination product.
• All patients swallowed the placebo tablets on their first attempt and reported no problems taking the tablets.
• The SYMTUZA placebo tablets were rated as easy to swallow by 93% (25/27) of patients.
• The acceptability of taking a SYMTUZA tablet every day over a long period was rated good by 52% (14/27) of patients and acceptable by 41% (11/27).

Additional Studies with DRV + COBI

McFarland Study (GS-US-216-0128)

McFarland et al (2017)² conducted a study in HIV-1–infected adolescents in order to determine pharmacokinetics (PK), safety, and efficacy of switching from DRV/RTV or atazanavir (ATV)/RTV to DRV + COBI or ATV + COBI, both in combination with 2 NRTIs.

Study Design/Methods

• Open-label switch study.
• HIV-1-infected, virologically-suppressed adolescents 12 to <18 years of age that were receiving DRV/RTV + 2 NRTIs or ATV/RTV + 2 NRTIs, had VL <50 copies/mL for ≥3 months, CD4+ count ≥200 cells/μL, and estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m² were eligible for inclusion.
• Patients received COBI 150 mg QD (adult dose), along with 1 of the following protease inhibitors (weight-based, QD dose): DRV 800 mg for ≥40 kg or 675 mg for 30 to <40 kg; ATV 300 mg for ≥40 kg or 200 mg for 20 to <40 kg.
• Other than PK, all other results were pooled.

Results

Baseline Characteristics

• There were 22 patients enrolled, eight (36%) who received DRV + COBI and 14 (64%) who received ATV + COBI.
• The median age was 14 years (range, 12-17 years).
• Median (quartile [Q] 1, Q3) duration of study drug exposure was 48 weeks (40, 61).

PK

• In the 7 DRV + COBI patients with PK data, the mean area under the curve for the dosing interval (AUC_tau) (% coefficient of variation [CV]) of DRV was found to be 81,200 (30) ng∙h/mL, compared to a historical value of 81,600 (32) ng∙h/mL in adult patients who received DRV 800 mg + COBI 150 mg QD in study GS-US-216-0130.
• The mean (%CV) DRV trough (C_tau) was 1310 (99) ng/mL, compared to a historical value of 1310 (74) ng/mL in adult patients.
• Median DRV exposures were also observed to be similar to those seen in adults, with the exception of a slightly lower C_tau level.
  • The median DRV C_tau level (494 ng/mL) was 9-fold above the half maximal inhibitory concentration (IC₅₀; 55 ng/mL).

Safety

• Study drug-related adverse events (AEs) were reported in 4/22 (18%) patients and were either grade 1 or 2. These included nausea (n=2), hyperlipidemia (n=2), decreased appetite (n=1), dyspepsia (n=1), and vomiting (n=1).
• Grade 3-4 AEs were reported in 3/22 (14%) and serious AEs were reported in 5/22 (23%); none were considered related to study drug.
• None of the patients discontinued treatment due to AEs, nor were any deaths reported.
• A small decline in median eGFR (-6.7 mL/min/1.73 m²) was noted and expected with COBI, which inhibits tubular secretion of creatinine.

Efficacy (Week 12)

• A total of 21/22 (95.5%) patients had VL<50 copies/mL (1 patient, who withdrew consent at week 8, had undetectable VL at withdrawal).
• Median (Q1, Q3) change in CD4+ cell count: -16 cells/μL (-254, 151).

Dalton Study

Dalton et al (2019)⁴ evaluated the tolerability and efficacy of DRV/COBI in 15 children.

Study Design/Methods

• This was a retrospective study using data from 2 National Health Service Trusts in the United Kingdom.

Results

• In 6/15 (40%) of the patients starting DRV/COBI, the only change in their regimen was the switch from RTV to COBI.
• At the time of data collection, 8/15 patients (53%) had stopped DRV/COBI (nausea/taste: n=3, poor adherence: n=3, simplification: n=1, and pill size: n=1).
• Patients who were suppressed at study entry maintained viral suppression.
• In patients with virological failure, no new HIV-1 associated resistance mutations were observed.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 15 September 2025.