Table of Contents
Credits
Host: Sara Dong
Guests: Camille Kotton, Roy Chemaly
Writing: Sara Dong (with clinical case from literature, cited below)
Edited and Produced by Sara Dong
Our Guests
Camille Kotton, MD
Camille Nelson Kotton MD, FIDSA, FAST is the clinical director of the Transplant Infectious Disease and Immunocompromised Host Program at the Massachusetts General Hospital, and Associate Professor of Medicine, Harvard Medical School, Boston, Massachusetts. She was chair of The Infectious Disease Community of Practice of The American Society of Transplantation (2012-2018). From 2007-2013, she was the president of The Transplant Infectious Disease Section of The Transplantation Society. Highlights of her time as president include the development of international guidelines on CMV management after solid organ transplant, published in Transplantation (2010, 2013, 2018). She is the first transplant infectious disease specialist to be a councilor of The Transplantation Society (2020). Her clinical interests include cytomegalovirus, donor-derived infections, zoonoses, and travel and tropical medicine in the transplant setting. She is a voting member of the CDC Advisory Committee on Immunization Practices (ACIP) and is involved in national decisions regarding COVID-19 and other vaccines.
Roy Chemaly, MD
Dr Roy Chemaly is the G. P. Bodey, Sr Distinguished Professor in Infectious Diseases and the newly appointed Chairman of the Department of Infectious Diseases, Infection Control, & Employee Health at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Chemaly completed his training in infectious diseases and medical microbiology at the Cleveland Clinic Foundation in Cleveland, Ohio. During his fellowship, Dr. Chemaly completed a master’s degree in public health from Northeastern Ohio Universities in Rootstown, Ohio. Other leadership appointments include the positions of vice-chair and past chair of the Infection Control Committee, the past chair of the Quality and Safety Council of the Division of Internal Medicine, and the past Chief Infection Control Officer at the University of Texas MD Anderson Cancer Center, Houston, Texas.
Dr Chemaly devoted his career studying viral infections in immunocompromised patients, specifically those undergoing hematopoietic cell transplantation (HCT) for hematologic malignancies. He published extensively on mechanisms to treat and prevent viral infections in this population. He contributed in writing and updating the practice guidelines for respiratory viruses, including SARS-CoV-2, in leukemia and HCT and Cellular Therapy patients for three major professional societies; the American Society of Transplantation and Cellular Therapy (ASTCT), the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), and the European Congress for Infectious Complications in Leukemia-8 (ECIL-8). Dr. Chemaly’s work has been reported in numerous high-impact peer-reviewed journals including the New England Journal of Medicine, Blood, Journal of Infectious Diseases, Clinical Microbiology and Infection, and Clinical Infectious Diseases.
Furthermore, Dr Chemaly is very well known on the national and international stages as an expert in clinical and translational virology in immunocompromised hosts. He is the co-chair of the Infection & Immune Reconstitution Working Committee of the ASTCT/CIBMTR, a member of the steering committee for the Transplant Associated Viral Infections (TAVI) that includes representation from the FDA, EMA, experts from national and international academic centers, and industry, the elected Vice-President of the International Immunocompromised Host Society (ICHS), and the chair for the working group on respiratory viruses (ESGREV) of the ESCMID. In addition, he is one of the founding members and past chair of the Transplant Infectious Diseases Special Interest Group of the ASTCT. He received numerous awards in 2022-2023 including the President’s Recognition of Faculty Excellence in Prevention Outreach, the Samuel J. Hassenbusch, M.D., Ph.D. Leadership and Institutional Service Award, the Gerald P. Bodey, Sr., Distinguished Professorship Award, all from the University of Texas MD Anderson Cancer Center, and finally the UT Healthcare COVID-19 Hero from the UT System Chancellor’s Council Executive Committee, Austin, Texas.
Culture
Camille shared the joy of traveling to visit and hear about the culture of different transplant programs around the world
Roy love the serenity of the first morning coffee to start the day
Consult Notes
We are back and live from IDWeek 2025!
Drs. Camille Kotton and Roy Chemaly join Febrile to discuss refractory Herpes Simplex Virus (HSV) infection in immunocompromised patients! This episode was recorded at an IDWeek 2025 affiliated event in Atlanta, GA on October 20, 2025.
You’ll find example cases and associated images referenced here:
- Shafat T, Ariza-Heredia EJ, Daher M, Chemaly RF. How we diagnose and manage refractory and resistant herpes simplex virus mucocutaneous infection after haematopoietic cell transplantation. Clin Microbiol Infect. 2025;31(5):761-772. doi:10.1016/j.cmi.2025.01.033
- Kotton BD, Kotton CN. Resistant herpes simplex virus infections – who, when, and what’s new?. Curr Opin Infect Dis. 2022;35(6):530-535. doi:10.1097/QCO.0000000000000889
What is refractory/resistant HSV?
- Defining refractory/resistant disease is important but for many years there was no standardized definition for refractory HSV infection
- Here is a key reference for this episode, a review of the literature and proposed definition for refractory/resistant HSV mucocutaneous infections for immunocompromised patients: Chemaly RF, Shafat T, Wald A, et al. Refractory and Resistant Herpes Simplex Virus Mucocutaneous Infections in Immunocompromised Patients: Literature Review and Proposed Definitions for Use in Clinical Trials. Clin Infect Dis. 2025;81(3):593-601. doi:10.1093/cid/ciae638
- A summary of definitions of refractory HSV mucocutaneous infection and antiviral drug resistance from that paper (available in Table 2) is available below. Although this was intended for clinical trials, it can also be used at the bedside
- Some additional summary references:
- Birkmann A, Saunders R. Overview on the management of herpes simplex virus infections: Current therapies and future directions. Antiviral Res. 2025;237:106152. doi:10.1016/j.antiviral.2025.106152
- Sallée L, Boutolleau D. Management of Refractory/Resistant Herpes Simplex Virus Infections in Haematopoietic Stem Cell Transplantation Recipients: A Literature Review. Rev Med Virol. 2024;34(5):e2574. doi:10.1002/rmv.2574
Mechanisms of antiviral resistance
- Acyclovir and valacyclovir are the primary drugs of choice for treatment and prevention of HSV infections in immunocompromised patients
- The antiviral activity depends on initial phosphorylation by a virus-encoded thymidine kinase (TK, encoded by UL23 gene) —> cellular kinases further phosphorylate the monophosphate to the active triphosphate form —> the active nucleotide analog is incorporated into the growing DNA strand by viral DNA polymerase (encoded by UL30) and prompts chain termination
- The primary mechanism of HSV-1/2 resistance is acquisition of mutation in the viral TK (95% of cases), resulting in absent or deficient viral TK, or a change in TK substrate specificity
- Here is a excellent figure summarizing the antiviral mechanisms:
Camille discussed the importance of making the diagnosis of refractory disease and then sending resistance testing. This testing can take several weeks to return though, so we still have to consider how to manage refractory disease prior to those results
Risk factors
Risk factors for refractory/resistant HSV infections in immunocompromised patients:
Roy and Camille discussed a proposed approach to the management of refractory and/or resistant HSV infection
Check out the algorithm below:
- We discussed the limitations of foscarnet alternative therapy, such as nephrotoxicity in particular
- Camille and Roy shared their experience with topical therapy (and the challenges of utilizing this as well including cost, compounding, potential toxicities)
- Camille and Roy also discussed pritelivir, an oral antiviral agent (helicase-primase complex inhibitor) that can address r/r HSV infections
- Roy mentioned the announcement of Phase 3 data where primary endpoint was met for pritelivir in immunocompromised patients with r/r mucocutaneous HSV: https://www.aicuris.com/press-release/aicuris-announces-pritelivir-met-primary-endpoint-in-immunocompromised-herpes-simplex-virus-infected-patients-in-phase-3-pivotal-trial/
- Camille is delivering a session at IDWeek 2025 on Phase 2 clinical data:
- Mon 10/20/25, 3:51-4:03PM in B213-214
- 233 – Efficacy and safety results from the Phase 2 clinical trial of pritelivir versus foscarnet for treatment of acyclovir-refractory and/or resistant mucocutaneous HSV infections in immunocompromised subjects
- The Early Access Program – still accepting patients: Study Details | NCT05844436 | Expanded Access Intermediate Size Treatment Protocol: Pritelivir for Immunocompromised Subjects with Treatment Resistant Herpes Simplex Virus Type 1 or 2 | ClinicalTrials.gov
- Some case reports of use of pritelivir:
- Purssell A, Leung K, Giguère P, Angel JB. Pritelivir for the Treatment of Nucleoside Analogue-Resistant Orolabial Herpes Simplex Virus 2 in a Person Living with HIV. J Assoc Med Microbiol Infect Dis Can. 2024;9(2):108-112. Published 2024 Jun 12. doi:10.3138/jammi-2023-0028
- Bussini L, Giardina AMF, Paolucci S, et al. Successful treatment and secondary prophylaxis with pritelivir for a recurrent multidrug-resistant herpes simplex virus 1 infection in an allogeneic haematopoietic stem cell transplant recipient. Clin Microbiol Infect. 2025;31(7):1234-1236. doi:10.1016/j.cmi.2025.04.011
- Bosetti D, Bernardi C, Maulini M, et al. Salvage Treatment of Refractory HSV Oral Lesions with Pritelivir in Allogeneic Hematopoietic Cell Transplant Recipients. Antimicrob Agents Chemother. 2023;67(4):e0173222. doi:10.1128/aac.01732-22
- Cannon L, Tholouli E, Ward C, Farooq H, Kingston M. Use of pritelivir in refractory aciclovir-resistant herpes simplex virus type 2. Int J STD AIDS. 2021;32(10):978-980. doi:10.1177/09564624211006568
- An additional review of pritelivir: Birkmann A, Bonsmann S, Kropeit D, et al. Discovery, Chemistry, and Preclinical Development of Pritelivir, a Novel Treatment Option for Acyclovir-Resistant Herpes Simplex Virus Infections. J Med Chem. 2022;65(20):13614-13628. doi:10.1021/acs.jmedchem.2c00668
- Don’t forget about reduction in immunosuppression !
Infographics
Goal
Listeners will be able to describe the epidemiology and management of refractory/resistant HSV infection in immunocompromised patients
Learning Objectives
After listening to this episode, listeners will be able to:
- Define and describe the epidemiology of refractory and/or resistant HSV in immunocompromised patients
- Describe the risk factors and outcomes associated with resistant/refractory HSV in immunocompromised patients
- Describe current treatment options for resistant/refractory HSV including their efficacy and safety/toxicity and why new treatments are needed
Disclosures
This episode was recorded at an IDWeek 2025 affiliated event in Atlanta, GA on October 20, 2025. Drs. Camille Kotton, Roy Chemaly, and Sara Dong were sponsored speakers by Aicuris Anti-infective Cures AG for this event, however this Febrile content was planned, produced, and reviewed solely by Febrile.
Citation
Kotton, C., Chemaly, R., Dong, S. “#124: Fulfilling an Unmet Need – Live from IDWeek 2025!”. Febrile: A Cultured Podcast. https://player.captivate.fm/episode/3383321f-ec92-4706-aa08-cbd9d3f1003e/