Effectiveness and safety of darunavir and lopinavir for treating children and adolescents living with HIV: a systematic review

INTRODUCTION: Darunavir and lopinavir solid formulations are recommended protease inhibitors for treating HIV. An evidence review of their effectiveness/efficacy and safety in young populations was needed to inform the 2025 World Health Organization guidelines. METHODS: We conducted a systematic review of publications reporting efficacy/effectiveness and/or safety of darunavir and/or lopinavir solid formulations in children and/or adolescents with HIV aged 0ƒ_”19 years, with at least 6 months follow-up. Sources included MEDLINE, Embase, Cochrane Library, recent HIV conferences and trial registries. Data were synthesized narratively. RESULTS: We screened 4,196 abstracts and 421 papers. Thirteen studies (including two randomized controlled trials (RCTs)) on darunavir were identified in 1,895 children/adolescents (2% treatment-naA_ve). Among treatment-experienced participants on ritonavir-boosted darunavir, 86% (198/229) and 95% (143/150) had viral suppression (<ƒ_%50 or <ƒ_%400 copies/mL) at 48 weeks in the RCTs and 29% (4/14)-100% (12/12) across seven other studies (Nƒ_%=ƒ_%736), respectively. Participants in the four studies (Nƒ_%=ƒ_%184) with <ƒ_%70% suppression were heavily treatment-experienced and unsuppressed at darunavir start. Grade 3/4 adverse events (clinical/laboratory) occurred in 0%-30% of participants on ritonavir-boosted darunavir (seven studies, Nƒ_%=ƒ_%515; 8ƒ_"9% in two large RCTs), and adverse events leading to discontinuation or treatment modification in 0%-10% (10 studies, Nƒ_%=ƒ_%974; 2ƒ_"3% in two RCTs). Three grade 3/4 adverse events in one study were drug related. Twenty-nine studies (including four randomized trials) on ritonavir-boosted lopinavir solid formulations were identified in 3,605 children/adolescents (17% treatment-naA_ve). Among treatment-experienced children/adolescents at 48ƒ_"52 weeks, viral suppression was 80% (179/223) in one RCT and 53% (448/852)-100% (12/12) across five other studies (Nƒ_%=ƒ_%1305). Across all populations, grade 3/4 adverse events were reported in 8%-60% of participants (four studies, Nƒ_%=ƒ_%1405; 8ƒ_"13% in two large RCTs), and events leading to discontinuation or treatment modification in 0%-9% (seven studies, Nƒ_%=ƒ_%905; 2ƒ_"3% in two RCTs). Five participants experienced drug-related grade 3/4 adverse events (five studies, Nƒ_%=ƒ_%1107). Lipid levels were significantly greater with lopinavir versus other regimens (five studies). CONCLUSIONS: Darunavir was safe in treatment-experienced children and adolescents, and viral suppression was high in RCTs; data were limited in treatment-naA_ve populations. Viral suppression with lopinavir solid formulations was variable. Lopinavir was generally well-tolerated but compared unfavourably with other drugs in terms of lipid outcomes. PROSPERO NUMBER: CRD42020204432. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-12511-z

• Population(s)
  • Children or Youth (less than 18 years old)
  • General HIV+ population
• Prevention, Engagement and Care Cascade
  • Engagement and Care Cascade
• Engagement and Care Cascade
  • Treatment
• Health Systems
  • Governance arrangements