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Schürmann D, Jackson Rudd D, Schaeffer A, et al. Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. J Acquir Immune Defic Syndr. 2022;89(2):191-198doi: 10.1097/QAI.0000000000002834.
Schürmann, D., Jackson Rudd, D., Schaeffer, A., De Lepeleire, I., Friedman, E. J., Robberechts, M., Zhang, S., Liu, Y., Kandala, B., Keicher, C., Däumer, M., Hofmann, J., Grobler, J. A., Stoch, S. A., Iwamoto, M., & Ankrom, W. (2022). Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. Journal of acquired immune deficiency syndromes (1999), 89(2), 191-198. https://doi.org/10.1097/QAI.0000000000002834
Schürmann, Dirk, et al. "Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week." Journal of acquired immune deficiency syndromes (1999) vol. 89,2 (2022): 191-198. doi: https://doi.org/10.1097/QAI.0000000000002834
Schürmann D, Jackson Rudd D, Schaeffer A, De Lepeleire I, Friedman EJ, Robberechts M, Zhang S, Liu Y, Kandala B, Keicher C, Däumer M, Hofmann J, Grobler JA, Stoch SA, Iwamoto M, Ankrom W. Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week. J Acquir Immune Defic Syndr. 2022 Feb 01;89(2):191-198. doi: 10.1097/QAI.0000000000002834. PMID: 34654041; PMCID: PMC8740605.
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J Acquir Immune Defic Syndr. 2022 Feb 01;89(2):191-198. doi: 10.1097/QAI.0000000000002834.

Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week.

Journal of acquired immune deficiency syndromes (1999)

Dirk Schürmann, Deanne Jackson Rudd, Andrea Schaeffer, Inge De Lepeleire, Evan J Friedman, Martine Robberechts, Saijuan Zhang, Yang Liu, Bhargava Kandala, Christian Keicher, Martin Däumer, Jörg Hofmann, Jay A Grobler, S Aubrey Stoch, Marian Iwamoto, Wendy Ankrom

Affiliations

  1. Charité Research Organisation GmbH, Berlin, Germany.
  2. Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  3. Merck & Co., Inc., Kenilworth, NJ.
  4. MSD, Brussels, Belgium.
  5. Seq-IT GmbH & Co. KG, Kaiserslautern, Germany; and.
  6. Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

PMID: 34654041 PMCID: PMC8740605 DOI: 10.1097/QAI.0000000000002834

Abstract

BACKGROUND: MK-8507 is a novel HIV-1 non-nucleoside reverse transcriptase inhibitor being developed for treatment of HIV-1 infection. MK-8507 has high antiviral potency in vitro and pharmacokinetic (PK) properties that support once-weekly dosing.

SETTING: A phase 1, open-label, proof-of-concept study was conducted in treatment-naive adults with HIV-1 infection to assess monotherapy antiviral activity.

METHODS: In 3 sequential panels, participants aged 18-60 years with baseline plasma HIV-1 RNA ≥10,000 copies/mL and CD4+ T-cell count >200/mm3 received a single oral dose of 40, 80, or 600 mg MK-8507 in the fasted state. Participants were assessed for HIV-1 RNA for at least 7 days, PKs for 14 days, and safety and tolerability for 21 days postdose.

RESULTS: A total of 18 participants were enrolled (6 per panel). The mean 7-day postdose HIV-1 RNA reduction ranged from ∼1.2 to ∼1.5 log10 copies/mL across the doses assessed. One patient had a viral rebound associated with emergence of an F227C reverse transcriptase variant (per chain-termination method sequencing) 14 days postdose; this variant was found in a second participant by ultra-deep sequencing as an emerging minority variant. MK-8507 PKs were generally dose-proportional and similar to observations in participants without HIV-1 infection in prior studies; mean MK-8507 half life was 56-69 hours in this study. MK-8507 was generally well tolerated at all doses.

CONCLUSIONS: The robust antiviral activity, PK, and tolerability of MK-8507 support its continued development as part of a complete once weekly oral regimen for HIV-1 treatment; combination therapy could mitigate the emergence of resistance-associated variants.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

References

  1. Diabetes Metab Syndr Obes. 2016 Jun 28;9:201-5 - PubMed
  2. Clin Transl Sci. 2016 Aug;9(4):192-200 - PubMed
  3. Curr Opin HIV AIDS. 2015 Jul;10(4):219-25 - PubMed
  4. J Antimicrob Chemother. 2020 Apr 1;75(4):1026-1030 - PubMed
  5. Antimicrob Agents Chemother. 2012 Nov;56(11):5938-45 - PubMed
  6. HIV Med. 2018 Aug;19 Suppl 3:5-23 - PubMed
  7. Clin Ther. 2015 Aug;37(8):1813-21.e1 - PubMed
  8. Front Pharmacol. 2017 Nov 23;8:831 - PubMed
  9. Antimicrob Agents Chemother. 2012 Jun;56(6):3101-6 - PubMed
  10. J Infect Dis. 2005 Feb 1;191(3):339-47 - PubMed
  11. Infect Dis Rep. 2013 Jun 06;5(Suppl 1):e5 - PubMed
  12. PLoS Med. 2016 Nov 29;13(11):e1002183 - PubMed
  13. AIDS. 2002 May 3;16(7):1051-8 - PubMed
  14. Clin Ther. 2001 Aug;23(8):1296-310 - PubMed
  15. Br J Clin Pharmacol. 2015 Feb;79(2):182-94 - PubMed
  16. Nat Med. 2000 Nov;6(11):1290-2 - PubMed
  17. Antimicrob Agents Chemother. 2003 Nov;47(11):3393-9 - PubMed
  18. Clin Infect Dis. 2019 Feb 1;68(4):535-544 - PubMed
  19. Int J Environ Res Public Health. 2019 Dec 09;16(24): - PubMed
  20. Antivir Ther. 2016;21(5):405-12 - PubMed
  21. AIDS. 2001 Jun 15;15(9):1181-3 - PubMed
  22. Patient Prefer Adherence. 2016 Jul 22;10:1299-307 - PubMed
  23. Lancet. 2013 Nov 2;382(9903):1525-33 - PubMed
  24. J Acquir Immune Defic Syndr. 2012 Jan 1;59(1):39-46 - PubMed
  25. JAMA Netw Open. 2020 Jun 1;3(6):e207954 - PubMed

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