Background
Nucleoside reverse transcriptase inhibitors (NRTIs) in combination with boosted protease inhibitors (PIs) are a recommended treatment for children with HIV-1 with resistance or intolerability to integrase strand transfer inhibitors. In the US, emtricitabine/tenofovir alafenamide (F/TAF) is approved in combination with boosted PIs for adults and children weighing ≥35 kg. TAF has improved renal and bone safety compared with tenofovir disoproxil fumarate. An ongoing Phase 2/3 open-label trial is evaluating F/TAF in combination with cobicistat-boosted atazanavir (ATV/co) or darunavir (DRV/co) in children with HIV-1 (NCT02016924). We present efficacy and safety outcomes through Week 24 in children aged 2-<12 y and weighing 14-<40 kg.
Methods
Participants aged 6-<12 y, weighing 25-<40 kg, receive 200/25 mg F/TAF + ATV/co or DRV/co (Cohort 2); participants ≥2 y and 14-<25 kg receive 120/15 mg F/TAF + ATV/co or DRV/co (Cohort 3). Key inclusion criteria are CD4 count ≥200 cells/µL, estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2, and on two NRTIs plus a third agent with no regimen changes within 3 months. Virologic suppression was assessed by FDA Snapshot algorithm; bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry of spine and total body less head (TBLH).
Results
Twenty-three (Cohort 2) and 26 (Cohort 3) participants enrolled. At baseline, in Cohorts 2 and 3 respectively, 61% and 54% participants were female, 91% and 92% were Black, median age (range) was 10 (8-12) and 6 (3-10) y, median (quartile [Q] 1, Q3) CD4 counts were 876 (671, 1063) and 940 (705, 1259) cells/µL, median (Q1, Q3) CD4 % was 36 (31, 41) and 35 (30, 41), and 96% and 92% had HIV-1 RNA <50 copies/mL. At Week 24, CD4 counts were similar to baseline, and 96% in each cohort had HIV-1 RNA <50 copies/mL. Two participants in Cohort 3 experienced Grade 3/4 study drug–related treatment-emergent adverse events (TEAEs) of increased bilirubin, considered related to ATV; one was classified as a serious TEAE. No Grade 3/4 or serious study drug–related TEAEs were reported in Cohort 2. Changes in height, weight, and body mass index Z-scores; spine and TBLH BMD; and eGFR were not clinically significant (Table).
Conclusions
In this interim analysis, F/TAF in combination with ATV/co or DRV/co in children aged 2-<12 y and weighing 14-<40 kg was efficacious, with an acceptable safety profile and no renal, bone, or weight concerns, supporting further evaluation in pediatric populations.
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