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 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.