Efficacy, Safety, and Tolerability of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Results Through Week 96 from IMPAACT 2014.
HIV-1
MK-1439A
adolescents
doravirine
Journal
Journal of the Pediatric Infectious Diseases Society
ISSN: 2048-7207
Titre abrégé: J Pediatric Infect Dis Soc
Pays: England
ID NLM: 101586049
Informations de publication
Date de publication:
16 Dec 2023
16 Dec 2023
Historique:
received:
24
05
2023
accepted:
27
09
2023
medline:
18
12
2023
pubmed:
10
10
2023
entrez:
10
10
2023
Statut:
ppublish
Résumé
IMPAACT 2014 study is a phase I/II, multicenter, open-label, nonrandomized study of doravirine (DOR) co-formulated with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) as fixed-dose combination (DOR FDC) in adolescents with HIV-1. We report the efficacy, safety, and tolerability of DOR FDC through 96 weeks. Participants were adolescents aged 12 to <18 years who weighed at least 45 kg and who were either antiretroviral (ARV)-naïve or virologically suppressed without documented resistance mutations to DOR/3TC/TDF. The efficacy endpoint was the proportion of participants with HIV-1 RNA <40 copies/mL assessed at weeks 48 and 96 using the observed failure approach. Safety and tolerability outcomes were incidence of adverse events (AEs) and treatment discontinuations. A total of 45 adolescents, median age 15 (range, 12-17) years, 58% females, were enrolled and 2 (4.4%) participants were ARV naïve. Of the 45 participants, 42 (93.3%) completed the study and 41 (91.1%) completed the study treatment. At week 48, 41/42 (97.6%; 95% confidence interval [CI], 87.4-99.9) and week 96, 37/40 (92.5%; 95% CI, 79.6-98.4) participants had achieved or maintained HIV-1 RNA <40 copies/mL. There were no treatment-related discontinuations due to AEs and no drug-related AEs ≥grade 3 or deaths. We found once-daily dosing of DOR FDC to be safe and well tolerated for maintaining viral suppression through 96 weeks in adolescents living with HIV-1.
Sections du résumé
BACKGROUND
BACKGROUND
IMPAACT 2014 study is a phase I/II, multicenter, open-label, nonrandomized study of doravirine (DOR) co-formulated with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) as fixed-dose combination (DOR FDC) in adolescents with HIV-1. We report the efficacy, safety, and tolerability of DOR FDC through 96 weeks.
METHODS
METHODS
Participants were adolescents aged 12 to <18 years who weighed at least 45 kg and who were either antiretroviral (ARV)-naïve or virologically suppressed without documented resistance mutations to DOR/3TC/TDF. The efficacy endpoint was the proportion of participants with HIV-1 RNA <40 copies/mL assessed at weeks 48 and 96 using the observed failure approach. Safety and tolerability outcomes were incidence of adverse events (AEs) and treatment discontinuations.
RESULTS
RESULTS
A total of 45 adolescents, median age 15 (range, 12-17) years, 58% females, were enrolled and 2 (4.4%) participants were ARV naïve. Of the 45 participants, 42 (93.3%) completed the study and 41 (91.1%) completed the study treatment. At week 48, 41/42 (97.6%; 95% confidence interval [CI], 87.4-99.9) and week 96, 37/40 (92.5%; 95% CI, 79.6-98.4) participants had achieved or maintained HIV-1 RNA <40 copies/mL. There were no treatment-related discontinuations due to AEs and no drug-related AEs ≥grade 3 or deaths.
CONCLUSIONS
CONCLUSIONS
We found once-daily dosing of DOR FDC to be safe and well tolerated for maintaining viral suppression through 96 weeks in adolescents living with HIV-1.
Identifiants
pubmed: 37815035
pii: 7303744
doi: 10.1093/jpids/piad078
doi:
Substances chimiques
Anti-HIV Agents
0
Anti-Retroviral Agents
0
doravirine
913P6LK81M
Lamivudine
2T8Q726O95
RNA
63231-63-0
Tenofovir
99YXE507IL
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
602-609Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI068616
Pays : United States
Investigateurs
Justine Beck
(J)
Thucuma Sise
(T)
Bill G Kapogiannis
(BG)
Kathleen George
(K)
Patricia Morgan
(P)
Yvonne Woolwine-Cunningham
(Y)
Rebecca Leblanc
(R)
Kathleen Trabert
(K)
Jeanne Mendell
(J)
Carmelita Alvero
(C)
Mona Farhad
(M)
Sarah Pasyar
(S)
Petronella Muresan
(P)
Nehali Patel
(N)
Adrienne English
(A)
Ryan Heince
(R)
Sandra Jones
(S)
Ellen Cooper
(E)
Debra McLaud
(D)
Elizabeth McFarland
(E)
Shane Curran Hays
(SC)
Jennifer Dunn
(J)
Kacey Navarro
(K)
Amanda Robson
(A)
Hilda Ndiwani
(H)
Ruth Mathiba
(R)
Avy Violari
(A)
Nastassja Ramsagar
(N)
Nuntisa Chotirosniramit
(N)
Chintana Khamrong
(C)
Jiraporn Chantong
(J)
Angkana Srita
(A)
Tim R Cressey
(TR)
Praornsuda Sukrakanchana
(P)
Kanyanee Kaewmamuang
(K)
Yupawan Thaweesombat
(Y)
Nirun Vanprapar
(N)
Kulkanya Chokephaibulkit
(K)
Nantaka Kongstan
(N)
Watcharee Lermankul
(W)
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.