SHIELD study: a multicenter, open-label, single-arm trial to evaluate the safety, pharmacokinetics and antiviral activity of fostemsavir in combination with optimized background therapy (OBT) in children and adolescents with HIV who are failing their current combination antiretroviral therapy (cART) and have dual- or triple-class antiretroviral (ARV) resistance

BACKGROUND: Multi-drug resistant HIV-1 is a growing global concern in children, highlighting the need for new antiretroviral drugs. Fostemsavir, recently approved for adults with multi-drug resistant HIV-1 and limited treatment options, has not yet been evaluated in the pediatric population. The SHEILD protocol was developed to assess this missing research gap. METHODS: The SHIELD study is a multicenter, phase I/II, open-label, single-arm trial evaluates the safety, pharmacokinetics and antiviral activity of fostemsavir in combination with optimized background therapy (OBT) in children and adolescents with HIV-1 who are failing their current combination antiretroviral therapy and have at least dual-class resistance. Participants will receive weight-based fostemsavir dosing: 400 mg twice daily for participants ≥20 to < 35 kg, and 600 mg twice daily for those ≥35 kg. It is planned to recruit at least 28 evaluable participants, including at least 8 participants under 12 years old weighing ≥20 kg to < 35 kg, of whom at least 4 must weigh ≥20 to < 25 kg. Participants will be treated for a minimum of 24 weeks, with safety follow-up continuing to 48 weeks. It is planned that those children benefiting from fostemsavir treatment may continue for up to 156 weeks to assess long-term safety. DISCUSSION: This registrational trial will generate data supporting the approval of fostemsavir for pediatric patients aged ≥6 years and weighing ≥20 kg. TRIAL REGISTRATION: Protocol number: PENTA 22/ViiV 212,968. EudraCT: 2020-001029-30. Clinicaltrials.gov: NCT04648280; Registration date: 11 November 2020.