Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Feb 1;92(2):153-161.
doi: 10.1097/QAI.0000000000003116.

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

Ann J Melvin  1 , Ka Lai Yee  2 , Kathryn P Gray  3   4 , Mounika Yedla  4 , Hong Wan  2 , Nicole H Tobin  5 , Hedy Teppler  2 , Havilland Campbell  2 , Katie McCarthy  6 , Rachel Scheckter  6 , Linda Aurpibul  7 , Pradthana Ounchanum  8 , Supattra Rungmaitree  9 , Hassena Cassim  10 , Elizabeth McFarland  11 , Patricia Flynn  12 , Ellen Cooper  13 , Chelsea Krotje  14 , Ellen Townley  15 , Jack Moye  16 , Brookie M Best  17 ; IMPAACT 2014 study team
Affiliations

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

Ann J Melvin et al. J Acquir Immune Defic Syndr. .

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) AUC 0-∞ was 34.8 μM∙hour, and the GM C 24 was 514 nM after a single dose, with a predicted steady-state GM C 24,ss,pred of 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.

PubMed Disclaimer

Conflict of interest statement

K.L.Y., H.W., H.T. (now retired), and H.C. hold stock and are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD) [license holder Pifeltro and Delstrigo]. P.F. participates on a Merck safety monitoring committee for non-HIV drugs. For the remaining authors, no conflicts of interest were disclosed.

Figures

Figure 1:
Figure 1:
Plasma Concentrations in Adolescents and Adults Following Single Dose Administration of 100 mg Doravirine Tablets
See this image and copyright information in PMC

References

    1. Brady MT, Oleske JM, Williams PL, et al. Declines in mortality rates and changes in causes of death in HIV-1-infected children during the HAART era. J Acquir Immune Defic Syndr. 2010;53(1):86–94. - PMC - PubMed
    1. Chiappini E, Larotonda F, Lisi C, et al. Real-World Analysis of Survival and Clinical Events in a Cohort of Italian Perinatally HIV-1 Infected Children From 2001 to 2018. Front Pediatr. 2021;9:665764. - PMC - PubMed
    1. Kapogiannis BG, Soe MM, Nesheim SR, et al. Mortality trends in the US Perinatal AIDS Collaborative Transmission Study (1986–2004). Clin Infect Dis. 2011;53(10):1024–1034. - PMC - PubMed
    1. Bratholm C, Johannessen A, Naman E, et al. Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. J Antimicrob Chemother. 2010;65(9):1996–2000. - PMC - PubMed
    1. Salou M, Dagnra AY, Butel C, et al. High rates of virological failure and drug resistance in perinatally HIV-1-infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo. Journal of the International AIDS Society. 2016;19(1):20683. - PMC - PubMed

Publication types