Assistance Publique-Hôpitaux de Paris, Université Sorbonne Paris Nord, Paris, France.
AP-HP, Centre National de Référence Herpèsvirus (Laboratoire Associé), Hôpital Pitié-Salpêtrière, Service de Virologie, and Sorbonne Université, INSERM, UMR-S 1136, Institut Pierre Louis d'Épidémiologie et de Santé Publique (iPLESP), Paris, France.
Rev Med Virol. 2024 Sep;34(5):e2574. doi: 10.1002/rmv.2574.
Herpes simplex virus (HSV) infections in allogeneic haematopoietic stem cell transplantation (HSCT) recipients pose significant challenges, with higher incidence, severity, and risk of emergence of resistance to antivirals due to impaired T-cell mediated immunity. This literature review focuses on acyclovir-refractory/resistant HSV infections in HSCT recipients. The review addresses the efficacy of antiviral prophylaxis, the incidence of acyclovir-refractory/resistant HSV infections, and the identification of risk factors and potential prognostic impact associated with those infections. Additionally, alternative therapeutic options are discussed. While acyclovir prophylaxis demonstrates a significant benefit in reducing HSV infections in HSCT recipients and, in some cases, overall mortality, concerns arise about the emergence of drug-resistant HSV strains. Our systematic review reports a median incidence of acyclovir-resistant HSV infections of 16.1%, with an increasing trend in recent years. Despite limitations in available studies, potential risk factors of emergence of HSV resistance to acyclovir include human leucocyte antigen (HLA) mismatches, myeloid neoplasms and acute leukaemias, and graft-versus-host disease (GVHD). Limited evidences suggest a potentially poorer prognosis for allogeneic HSCT recipients with acyclovir-refractory/resistant HSV infection. Alternative therapeutic approaches, such as foscarnet, cidofovir, topical cidofovir, optimised acyclovir dosing, and helicase-primase inhibitors offer promising options but require further investigations. Overall, larger studies are needed to refine preventive and therapeutic strategies for acyclovir-refractory/resistant HSV infections in allogeneic HSCT recipients and to identify those at higher risk.
异基因造血干细胞移植（HSCT）受者的单纯疱疹病毒（HSV）感染带来了重大挑战，由于 T 细胞介导的免疫受损，HSV 感染的发生率、严重程度和抗病毒药物耐药风险更高。本文主要关注异基因 HSCT 受者中阿昔洛韦耐药/难治性 HSV 感染。本文回顾了抗病毒预防的疗效、阿昔洛韦耐药/难治性 HSV 感染的发生率，以及与这些感染相关的风险因素和潜在预后影响的识别，此外还讨论了替代治疗选择。虽然阿昔洛韦预防可显著降低 HSCT 受者 HSV 感染的发生率，并且在某些情况下降低总体死亡率，但人们对耐药性 HSV 株的出现表示担忧。我们的系统评价报告了阿昔洛韦耐药 HSV 感染的中位数发生率为 16.1%，近年来呈上升趋势。尽管受限于现有研究，阿昔洛韦耐药性 HSV 出现的潜在危险因素包括人类白细胞抗原（HLA）不匹配、髓系肿瘤和急性白血病以及移植物抗宿主病（GVHD）。有限的证据表明，阿昔洛韦耐药/难治性 HSV 感染的异基因 HSCT 受者的预后可能更差。替代治疗方法，如膦甲酸、更昔洛韦、局部更昔洛韦、优化阿昔洛韦剂量和解旋酶-引物抑制剂提供了有前途的选择，但需要进一步研究。总体而言，需要更大规模的研究来完善异基因 HSCT 受者中阿昔洛韦耐药/难治性 HSV 感染的预防和治疗策略，并确定那些风险更高的患者。
