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

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. 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. This registrational trial will generate data supporting the approval of fostemsavir for pediatric patients aged ≥6 years and weighing ≥20 kg. Protocol number: PENTA 22/ViiV 212,968. EudraCT: 2020-001029-30. Clinicaltrials.gov: NCT04648280; Registration date: 11 November 2020.