Pharmacokinetics, Tolerability, and Safety of Doravirine and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living with HIV: Week 24 Results from IMPAACT 2014
Issued Date
2023-02-01
Resource Type
ISSN
15254135
eISSN
10779450
Scopus ID
2-s2.0-85146140094
Pubmed ID
36215957
Journal Title
Journal of Acquired Immune Deficiency Syndromes
Volume
92
Issue
2
Start Page
153
End Page
161
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Acquired Immune Deficiency Syndromes Vol.92 No.2 (2023) , 153-161
Suggested Citation
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. Pharmacokinetics, Tolerability, and Safety of Doravirine and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living with HIV: Week 24 Results from IMPAACT 2014. Journal of Acquired Immune Deficiency Syndromes Vol.92 No.2 (2023) , 153-161. 161. doi:10.1097/QAI.0000000000003116 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82432
Title
Pharmacokinetics, Tolerability, and Safety of Doravirine and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living with HIV: Week 24 Results from IMPAACT 2014
Author(s)
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.
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.
Author's Affiliation
Siriraj Hospital
Skaggs School of Pharmacy & Pharmaceutical Sciences
FHI 360
Frontier Science & Technology Research Foundation, Inc.
Harvard T.H. Chan School of Public Health
University of Colorado School of Medicine
St. Jude Children's Research Hospital
Children's Hospital and Regional Medical Center
National Institute of Child Health and Human Development (NICHD)
National Institute of Allergy and Infectious Diseases (NIAID)
University of the Witwatersrand, Johannesburg
University of Washington
Merck & Co., Inc.
David Geffen School of Medicine at UCLA
Boston Medical Center
Chiang Mai University
AMS-CMU & IRD Research Collaboration
NIAID/DAIDS
Merck
Frontier Science Foundation
University of Colorado
St. Jude CRS
NICHD
Chiangrai Prachanukroh Hospital
Chiangrai Prachanukroh Hospital
Skaggs School of Pharmacy & Pharmaceutical Sciences
FHI 360
Frontier Science & Technology Research Foundation, Inc.
Harvard T.H. Chan School of Public Health
University of Colorado School of Medicine
St. Jude Children's Research Hospital
Children's Hospital and Regional Medical Center
National Institute of Child Health and Human Development (NICHD)
National Institute of Allergy and Infectious Diseases (NIAID)
University of the Witwatersrand, Johannesburg
University of Washington
Merck & Co., Inc.
David Geffen School of Medicine at UCLA
Boston Medical Center
Chiang Mai University
AMS-CMU & IRD Research Collaboration
NIAID/DAIDS
Merck
Frontier Science Foundation
University of Colorado
St. Jude CRS
NICHD
Chiangrai Prachanukroh Hospital
Chiangrai Prachanukroh Hospital
Other Contributor(s)
Abstract
Background: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.