Hovilpri (Pritelivir) Oral Anti-HSV: Immunocompromised Adults With Acyclovir-Refractory Mucocutaneous Lesions, 63% Healing at 28 Days

　　1.Disease and Eligibility

　　HSV-1 and HSV-2 cause painful vesicular and erosive lesions on lips,nares,eyes,genitals,and other skin or mucous membranes,then establish latency with recurrent reactivation.Immunocompetent patients usually respond to acyclovir-class therapy.Immunocompromised populations—hematologic malignancy,stem-cell or solid-organ transplant,HIV,chemotherapy,or immunosuppressive therapy for autoimmune/inflammatory disease—have more frequent,severe,or prolonged outbreaks and higher risk of inadequate response or resistance.

　　Hovilpri is for adults who are immunocompromised with mucocutaneous HSV that did not respond to acyclovir,valacyclovir,or famciclovir,with or without confirmed resistance.It is not for routine immunocompetent recurrences,isolated systemic infection without mucosal/skin lesions,or automatic replacement of site-specific guidelines such as HSV encephalitis or keratitis unless an infectious disease team重新evaluates susceptibility and local therapy.

　　2.Mechanism and Clinical Value

　　Pritelivir inhibits the HSV helicase-primase complex required for viral DNA replication,a different target from thymidine kinase/DNA polymerase pathways used by acyclovir-class drugs.It can retain activity against some HSV-1/HSV-2 strains resistant through TK or DNA polymerase mutations and offers an oral option when intravenous therapy is undesirable.It does not eradicate latency and should not be presented as a cure;post-healing suppression depends on underlying immune recovery and virologic follow-up.

　　3.Key Trial Data

　　PRIOH-1 phase 3 part C(NCT03073967)was randomized,open-label,active-controlled,and superiority-designed,enrolling 101 immunocompromised adults with acyclovir-class-refractory mucocutaneous HSV.The pritelivir arm used a 400mg loading dose on day 1 followed by 100mg once daily;the comparator arm used investigator-selected therapy such as intravenous foscarnet,intravenous or topical cidofovir,or 5%imiquimod.Maximum treatment was 28 days,extended to 42 days if lesions improved but were not fully healed.

　　Primary endpoint—complete healing of all lesions by day 28—occurred in 63%with pritelivir versus 34%with comparators;adjusted difference 28.4%(95%CI 9.6–47.3,P=0.0047).By day 42,complete healing was about 82%versus 42%.Any-grade adverse events were about 22%with pritelivir and 54%with comparators;discontinuation for adverse events was about 2%versus 20%;headache was most common.These results apply to standard-therapy-refractory immunosuppressed patients,not to first-episode immunocompetent herpes.

　　4.Dosing and Safety Monitoring

　　Base maintenance on 100mg once daily after a 400mg loading dose per full prescribing information;modify for immune status,renal function,concurrent antivirals,and comparator switching.Extend to 42 days only for partial improvement,and stop once all lesions heal under specialist review.Do not add other antivirals,immunosuppressants,or oncology drugs without interaction assessment.

　　Safety priorities:

　　Headache is most common;persistent or severe headache requires exclusion of CNS infection or other causes.

　　In immunocompromised patients,watch for secondary bacterial infection,ocular involvement,and extensive oropharyngeal/esophageal lesions affecting nutrition.

　　Transplant recipients using tacrolimus,cyclosporine,or mTOR inhibitors need drug-level and renal monitoring;do not adjust empirically.

　　HIV patients need antiretroviral compatibility review to maintain viral suppression.

　　Hematology/chemotherapy patients need neutrophil,renal,and electrolyte monitoring;organ-transplant patients need graft-function monitoring.

　　Any rash,jaundice,oliguria,visual change,or mental-status change warrants urgent review.

　　5.Patient Counseling

　　This is not a universal“stronger herpes pill”but a targeted option for immunocompromised patients failing older oral antivirals or with resistance.Bring prior HSV culture/PCR,resistance testing,acyclovir-class treatment history,reason for immunosuppression,and all prescription lists.Record lesion count,discharge,pain,feeding,and temperature;reassess at 28 days,discuss extension if improving,and re-test for mixed infection or alternative viruses if no improvement.Do not use unapproved cross-border versions or stop immunosuppressive disease therapy solely because an oral antiviral is started.