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Review

Optimizing Antiviral Dosing for HSV and CMV Treatment in Immunocompromised Patients

by
Daan W. Huntjens
1,†,
Jacob A. Dijkstra
1,*,†,
Lisanne N. Verwiel
1,
Mirjam Slijkhuis
1,
Paul Elbers
2,
Matthijs R. A. Welkers
3,
Agnes I. Veldkamp
1,
Marianne A. Kuijvenhoven
1,
David C. de Leeuw
4,
Heshu Abdullah-Koolmees
1,5,6,
Maria T. Kuipers
4 and
Imke H. Bartelink
1,7
1
Pharmacy & Clinical Pharmacology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
2
Department of Intensive Care Medicine, Laboratory for Critical Care Computational Intelligence (LCCI), Amsterdam Medical Data Science (AMDS), Amsterdam Cardiovascular Science (ACS), Amsterdam Institute for Infection and Immunity (AII), Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
3
Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
4
Hematology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
5
Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Postbus 85500, 3508 GA Utrecht, The Netherlands
6
Clinical Pharmacy, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
7
Cancer Center Amsterdam, 1081HV Amsterdam, The Netherlands
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Pharmaceutics 2023, 15(1), 163; https://doi.org/10.3390/pharmaceutics15010163
Submission received: 8 December 2022 / Revised: 27 December 2022 / Accepted: 28 December 2022 / Published: 3 January 2023
(This article belongs to the Special Issue Dose Optimization and Targeting Strategies of Anti-infective Agents)
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Abstract

Herpes simplex virus (HSV) and cytomegalovirus (CMV) are DNA viruses that are common among humans. Severely immunocompromised patients are at increased risk of developing HSV or CMV disease due to a weakened immune system. Antiviral therapy can be challenging because these drugs have a narrow therapeutic window and show significant pharmacokinetic variability. Above that, immunocompromised patients have various comorbidities like impaired renal function and are exposed to polypharmacy. This scoping review discusses the current pharmacokinetic (PK) and pharmacodynamic (PD) knowledge of antiviral drugs for HSV and CMV treatment in immunocompromised patients. HSV and CMV treatment guidelines are discussed, and multiple treatment interventions are proposed: early detection of drug resistance; optimization of dose to target concentration by therapeutic drug monitoring (TDM) of nucleoside analogs; the introduction of new antiviral drugs; alternation between compounds with different toxicity profiles; and combinations of synergistic antiviral drugs. This research will also serve as guidance for future research, which should focus on prospective evaluation of the benefit of each of these interventions in randomized controlled trials.
Keywords: antiviral agents; therapeutic drug monitoring; immune deficiency; allogeneic transplantation; herpesvirus 1; human; herpesvirus 2; human; cytomegalovirus antiviral agents; therapeutic drug monitoring; immune deficiency; allogeneic transplantation; herpesvirus 1; human; herpesvirus 2; human; cytomegalovirus

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MDPI and ACS Style

Huntjens, D.W.; Dijkstra, J.A.; Verwiel, L.N.; Slijkhuis, M.; Elbers, P.; Welkers, M.R.A.; Veldkamp, A.I.; Kuijvenhoven, M.A.; de Leeuw, D.C.; Abdullah-Koolmees, H.; et al. Optimizing Antiviral Dosing for HSV and CMV Treatment in Immunocompromised Patients. Pharmaceutics 2023, 15, 163. https://doi.org/10.3390/pharmaceutics15010163

AMA Style

Huntjens DW, Dijkstra JA, Verwiel LN, Slijkhuis M, Elbers P, Welkers MRA, Veldkamp AI, Kuijvenhoven MA, de Leeuw DC, Abdullah-Koolmees H, et al. Optimizing Antiviral Dosing for HSV and CMV Treatment in Immunocompromised Patients. Pharmaceutics. 2023; 15(1):163. https://doi.org/10.3390/pharmaceutics15010163

Chicago/Turabian Style

Huntjens, Daan W., Jacob A. Dijkstra, Lisanne N. Verwiel, Mirjam Slijkhuis, Paul Elbers, Matthijs R. A. Welkers, Agnes I. Veldkamp, Marianne A. Kuijvenhoven, David C. de Leeuw, Heshu Abdullah-Koolmees, and et al. 2023. "Optimizing Antiviral Dosing for HSV and CMV Treatment in Immunocompromised Patients" Pharmaceutics 15, no. 1: 163. https://doi.org/10.3390/pharmaceutics15010163

APA Style

Huntjens, D. W., Dijkstra, J. A., Verwiel, L. N., Slijkhuis, M., Elbers, P., Welkers, M. R. A., Veldkamp, A. I., Kuijvenhoven, M. A., de Leeuw, D. C., Abdullah-Koolmees, H., Kuipers, M. T., & Bartelink, I. H. (2023). Optimizing Antiviral Dosing for HSV and CMV Treatment in Immunocompromised Patients. Pharmaceutics, 15(1), 163. https://doi.org/10.3390/pharmaceutics15010163

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