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

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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 0–19 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-naïve). Among treatment-experienced participants on ritonavir-boosted darunavir, 86% (198/229) and 95% (143/150) had viral suppression (< 50 or < 400 copies/mL) at 48 weeks in the RCTs and 29% (4/14)-100% (12/12) across seven other studies (N = 736), respectively. Participants in the four studies (N = 184) with < 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, N = 515; 8–9% in two large RCTs), and adverse events leading to discontinuation or treatment modification in 0%-10% (10 studies, N = 974; 2–3% 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-naïve). Among treatment-experienced children/adolescents at 48–52 weeks, viral suppression was 80% (179/223) in one RCT and 53% (448/852)-100% (12/12) across five other studies (N = 1305). Across all populations, grade 3/4 adverse events were reported in 8%-60% of participants (four studies, N = 1405; 8–13% in two large RCTs), and events leading to discontinuation or treatment modification in 0%-9% (seven studies, N = 905; 2–3% in two RCTs). Five participants experienced drug-related grade 3/4 adverse events (five studies, N = 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-naïve 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.

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