Melvin A.J.Yee K.L.Gray K.P.Yedla M.Wan H.Tobin N.H.Teppler H.Campbell H.McCarthy K.Scheckter R.Aurpibul L.Ounchanum P.Rungmaitree S.Cassim H.McFarland E.Flynn P.Cooper E.Krotje C.Townley E.Moye J.Best B.M.Beck J.Sise T.Kapogiannis B.G.George K.Morgan P.Woolwine-Cunningham Y.Leblanc R.Trabert K.Mendell J.Alvero C.Farhad M.Pasyar S.Muresan P.Patel N.English A.Heince R.Jones S.McLaud D.Hays S.C.Dunn J.Navarro K.Robson A.Ndiwani H.Mathiba R.Violari A.Ramsagar N.Chotirosniramit N.Khamrong C.Jantong J.Cressy T.R.Sukrakanchana P.O.Thaweesombat Y.Kaewmamuang K.Vanprapar N.Chokephaibulkit K.Kongstan N.Lermankul W.Mahidol University2023-05-192023-05-192023-02-01Journal of Acquired Immune Deficiency Syndromes Vol.92 No.2 (2023) , 153-16115254135https://repository.li.mahidol.ac.th/handle/20.500.14594/82432Background:We studied the pharmacokinetics (PK) and safety of 100-mg doravirine and doravirine/lamivudine/tenofovir disoproxil fumarate fixed-dose combination (100/300/300 mg DOR FDC) treatment in adolescents with HIV-1.Methods:Adolescents ages 12 to younger than 18 years were enrolled in 2 sequential cohorts. Cohort 1 evaluated intensive PK and short-term safety of 100-mg single-dose doravirine in adolescents ≥35 kg. Cohort 2 participants either initiated treatment with DOR FDC (antiretroviral (ARV)-naïve) or switched to DOR FDC from a previous ARV regimen (virologically suppressed). The first 10 Cohort 2 participants had intensive PK evaluations, and safety, sparse PK, and HIV RNA were assessed through week 24.Results:Fifty-five adolescents, median age 15.0 years and baseline weight 51.5 kg, were enrolled. Nine participants completed Cohort 1 PK assessments (8 of the 9 participants weighed ≥45 kg) and 45 initiated study drug in Cohort 2. The doravirine geometric mean (GM) AUC0-∞was 34.8 Mhour, and the GM C24was 514 nM after a single dose, with a predicted steady-state GM C24,ss,predof 690 nM. Cohort 2 enrolled adolescents weighing ≥45 kg. Plasma concentrations of doravirine, tenofovir, and lamivudine achieved by Cohort 2 participants were similar to those reported in adults. No drug-related serious or grade 3 or 4 adverse events occurred. Forty-two of 45 participants (93.3%; 95% CI: [81.7, 98.6]) achieved or maintained HIV-1 RNA <40 copies/mL.Conclusions:Doravirine and DOR FDC achieved target PK in adolescents with HIV-1. DOR FDC was well-tolerated and maintained excellent virologic efficacy through 24 weeks, offering a favorable option for adolescents.MedicineArticleSCOPUS10.1097/QAI.00000000000031162-s2.0-851461400941077945036215957