Challenges of aciclovir-resistant HSV infection in allogeneic bone marrow transplant recipients

Antón-Vázquez, Vanesa; Mehra, Varun; Mbisa, Jean L.; Bradshaw, Daniel; Basu, Tanya; Daly, Marie-Louise; Mufti, Ghulam J.; Pagliuca, Antonio; Potter, Victoria; Zuckerman, Mark

doi:10.1016/j.jcv.2020.104421

Cited by 24 publications

(13 citation statements)

References 26 publications

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“…Literature review demonstrates a prevalence of acyclovir resistance of 14%-46.5% within HSCT recipients with clinically confirmed HSV infection, [11][12][13] -which is markedly higher than in immunocompetent patients. Concomitant GvHD is reported to be an additional significant risk factor for the development of antiviral resistance.…”

Section: Discussionmentioning

confidence: 99%

Unusual oral presentation of acyclovir-resistant herpes simplex in an allogeneic haematopoietic stem cell transplant recipient

2021

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The early engraftment phase of allogeneic haematopoietic stem cell transplantation can be associated with a number of oromucosal infective complications. While the routine use of prophylactic acyclovir has reduced the incidence of herpes simplex virus (HSV) reactivation, there is an increasing prevalence of acyclovir resistance within this cohort of patients. The authors present a case of acyclovir-resistant HSV reactivation in a 26-year-old woman 7 days post T-deplete sibling allograft on a background of combined cyclophosphamide and total body irradiation myeloablative conditioning, successfully treated with foscarnet and cidofovir therapy and discuss the differential diagnoses for early/late engraftment oral disease.

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Section: Discussionmentioning

confidence: 99%

Unusual oral presentation of acyclovir-resistant herpes simplex in an allogeneic haematopoietic stem cell transplant recipient

2021

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“…In immunocompetent individuals, the prevalence of nucleoside analogues’ resistance in HSV is still low (below 1%), but in immunocompromised HSV-infected patients, it varies from 2.5% to over 30%. The resistance rate depends on the degree of immunosuppression and underlying illness (the highest in HSC recipients under prolonged antiviral therapy) [ 27 , 44 , 63 , 64 , 65 ].…”

Section: Antiviral Drugsmentioning

confidence: 99%

“…Other indications for the use of CDV are infections caused by HSV and VZV resistant to ACV and/or FOS. CDV also acts as an inhibitor of other viruses: adenoviruses (HAdVs), polyomaviruses, human papillomaviruses (HPVs), and orthomyxoviruses [ 18 , 28 , 64 , 70 ]. CDV has limited bioavailability (5 to 22%) and is therefore given intravenously.…”

Section: Antiviral Drugsmentioning

confidence: 99%

40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?

Majewska

Młynarczyk-Bonikowska

2022

IJMS

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Herpes simplex virus types 1 and 2 HSV1 and 2, namely varicella-zoster VZV and cytomegalovirus CMV, are among the most common pathogens worldwide. They remain in the host body for life. The course of infection with these viruses is often asymptomatic or mild and self-limiting, but in immunocompromised patients, such as solid organ or bone marrow transplant recipients, the course can be very severe or even life-threatening. Unfortunately, in the latter group, the highest percentage of infections with strains resistant to routinely used drugs is observed. On the other hand, frequent recurrences of genital herpes can be a problem even in people with normal immunity. Genital herpes also increases the risk of acquiring sexually transmitted diseases, including HIV infection and, if present in pregnant women, poses a risk to the fetus and newborn. Even more frequently than herpes simplex, congenital infections can be caused by cytomegalovirus. We present the most important anti-herpesviral agents, the mechanisms of resistance to these drugs, and the associated mutations in the viral genome. Special emphasis was placed on newly introduced drugs such as maribavir and brincidofovir. We also briefly discuss the most promising substances in preclinical testing as well as immunotherapy options and vaccines currently in use and under investigation.

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“…This strategy may benefit the antiviral treatment but can lead to an increased risk of GvHD. In addition, the administration of intravenous immunoglobulin G (IVIG) is discussed frequently in literature [ 4 , 104 , 107 ]. No evident superiority compared to standard treatment has been demonstrated yet, and IVIG cannot replace antiviral treatment in acyclovir-resistant HSV infections in immunocompromised patients [ 104 , 107 ].…”

Section: Optimized Hsv and CMV Treatment Guidelinesmentioning

confidence: 99%

“…In addition, the administration of intravenous immunoglobulin G (IVIG) is discussed frequently in literature [ 4 , 104 , 107 ]. No evident superiority compared to standard treatment has been demonstrated yet, and IVIG cannot replace antiviral treatment in acyclovir-resistant HSV infections in immunocompromised patients [ 104 , 107 ]. CMV-IVIG may benefit immunocompromised patients with CMV pneumonia [ 4 ].…”

Section: Optimized Hsv and CMV Treatment Guidelinesmentioning

confidence: 99%

Optimizing Antiviral Dosing for HSV and CMV Treatment in Immunocompromised Patients

et al. 2023

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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.

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Challenges of aciclovir-resistant HSV infection in allogeneic bone marrow transplant recipients

Cited by 24 publications

References 26 publications

Unusual oral presentation of acyclovir-resistant herpes simplex in an allogeneic haematopoietic stem cell transplant recipient

Unusual oral presentation of acyclovir-resistant herpes simplex in an allogeneic haematopoietic stem cell transplant recipient

40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?

Optimizing Antiviral Dosing for HSV and CMV Treatment in Immunocompromised Patients

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