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Hovilpri (pritelivir)

Refractory mucocutaneous herpes simplex virus infection in immunocompromised adults

Also known as AIC316
Last updated
239 sources

Product information and disease descriptionPlace of product in therapyDisease description

Clinical presentation - signs and symptoms

12 evidence topics · 23 sources

Overall pattern: mucocutaneous lesions that are more extensive and persistent in immunocompromised hosts

“Most R/R HSV infections manifest with mucocutaneous lesions, including herpetic gingivostomatitis and herpes genitalis.” (opens the source at this quote in a new tab)

“Mucocutaneous infections resulting from herpes simplex virus (HSV) in hematopoietic cell transplant (HCT) recipients tend to be more aggressive, extensive, and persistent compared to immunocompetent individuals due to impaired immunity, cytopenia, poor nutritional status, graft-versus-host disease, and immunosuppressants” (opens the source at this quote in a new tab)

“Although in healthy patients clinical signs and symptoms of HSV infection are usually mild and self-limiting, HSV-infections in immunocompromised patients are frequently more aggressive, persistent, and even life-threatening.” (opens the source at this quote in a new tab)

“Compared with immunocompetent persons, SOT recipients shed HSV more frequently, have more severe clinical manifestations, and are slower to respond to therapy.” (opens the source at this quote in a new tab)

“Immunocompromised patients can have prolonged or severe episodes of genital, perianal, or oral herpes. Lesions caused by HSV are common among persons with HIV infection and might be severe, painful, and atypical” (opens the source at this quote in a new tab)

Distribution of lesion sites in the seven-center United States transplant cohort
Site or serotypeRecipients, N (%) of 125
Herpes simplex virus type 1“89 (71.2)”
Oral or facial“103 (82.4)”
Genital or perianal“23 (18.4)”
Other cutaneous“5 (4.0)”
System involvement“15 (12.0)”

“Eighty-two percent of patients had orofacial infections, and 18% of patients had genital and/or perineal infections. Eight patients (6.4%) had cutaneous lesions in ≥2 noncontiguous sites.” (opens the source at this quote in a new tab)

“More than 75% of the patients presented with refractory orofacial lesions caused by HSV-1.” (opens the source at this quote in a new tab)

Distribution of lesion sites and virus type in the five-center United States foscarnet cohort
CharacteristicEpisodes, No. (%) of 31
HSV-1“18 (58)”
HSV-2“14 (45)”
Oral“15 (48)”
Anogenital“12 (39)”
Oral and anogenital“3 (10)”
Other“1 (3)”

“There were slightly more HSV episodes due to HSV type 1 than HSV type 2, and there were more episodes exclusively involving oral mucosa than other sites or multiple sites.” (opens the source at this quote in a new tab)

Orolabial and oropharyngeal lesions

“Oral lesions were observed in all 18 cases, primarily on the tongue (n = 12) and lips (n = 11).” (opens the source at this quote in a new tab)

“The most involved oral site was the tongue (12 patients), followed by the lips (11 patients), buccal mucosa (six patients), hard palate (three patients), and soft palate (two patients). Details of the specific oral site were not recorded for four patients.” (opens the source at this quote in a new tab)

“Lesions were noted on the lining mucosa of all 18 patients, with only three patients demonstrating coexisting masticatory mucosal lesions (hard palate). This is in contrast to immunocompetent patients, who typically demonstrate HSV lesions on the masticatory mucosa.” (opens the source at this quote in a new tab)

“Twelve patients had oral/labial HSV infections identified as HSV1, and six patients had genital/perineal HSV infections identified as HSV2.” (opens the source at this quote in a new tab)

“All patients presented with hemorrhagic oral mucositis refractory to treatment dose ACV.” (opens the source at this quote in a new tab)

“Three cases corresponded to HSV-1, all with oral or facial involvement, and two cases to HSV-2, both perirectal” (opens the source at this quote in a new tab)

“The sites of mucocutaneous HSV lesions are the oro-facial region in 85-90% of cases and the genital area in 10-15% (I).” (opens the source at this quote in a new tab)

Genital and perianal lesions

“HSV-1 and HSV-2 are significant causes of proctitis in men with HIV who have sex with men and may occur in the absence of external anal ulcers.” (opens the source at this quote in a new tab)

“Perirectal HSV lesions are more likely to be resistant to acyclovir compared to lesions at other locations.” (opens the source at this quote in a new tab)

“Both clinical and subclinical reactivations of genital herpes are more frequent in people living with HIV and may lead to persistent and progressive anogenital mucocutaneous lesions” (opens the source at this quote in a new tab)

“Features can be atypical in nature and larger, deeper and hypertrophic lesions can occur.” (opens the source at this quote in a new tab)

“Twelve patients were men, nine patients were of African origin. All patients reported previous acyclovir exposure and median CD4 count was 183 cells/mm(3) Ten patients presented exclusively with cutaneous lesions.” (opens the source at this quote in a new tab)

“Three people living with HIV (PLHIV) had resistant anogenital HSV-2 infections.” (opens the source at this quote in a new tab)

“Among PLHIV, infections included recurrent genital herpes and atypical pseudo-tumoral lesions, managed with foscarnet or adjunctive topical cidofovir or imiquimod.” (opens the source at this quote in a new tab)

Chronic ulcerative lesions

“In profoundly immunocompromised people (CD4 counts <100 cells/mm3), extensive, deep, nonhealing ulcerations can occur.” (opens the source at this quote in a new tab)

“Chronic herpes simplex virus (CHSV) and chronic varicella zoster virus (CVZV) are defined as atypical mucocutaneous wart-like and/or ulcerative HSV or VZV infections, persisting for at least 1 month. Both are commonly associated with HIV infection and may occasionally present with other types of immunosuppression.” (opens the source at this quote in a new tab)

“Treatment is frequently complicated by resistance to thymidine kinase (TK)-dependent antivirals, including acyclovir, valacyclovir and famciclovir.” (opens the source at this quote in a new tab)

“Herpes simplex virus causes mucocutaneous disease early in the course HIV infection and ulcerative lesions at any site in advanced HIV infection.” (opens the source at this quote in a new tab)

“Acyclovir resistance is usually seen in patients with large, untreated, ulcerative lesions of herpes simplex virus and in patients with chronic, verrucous lesions of varicella-zoster virus.” (opens the source at this quote in a new tab)

Hypertrophic, pseudotumoral, and tumoral lesions

“From 110 reported patients, the following data were available: the patients' ages ranged from 7 to 76 years; the majority was male (62.73 %-69/110) and immunosuppression was found in 97.25 % (106/109, missing 1) cases, of whom 88 were HIV- related.” (opens the source at this quote in a new tab)

“Lesions size varied from 0.2-13 cm, settling in the anogenital region in 76.36 % (84/110) patients” (opens the source at this quote in a new tab)

“Type 2 HSV was detected in 86.07 % (68/79, missing 31) lesions.” (opens the source at this quote in a new tab)

“In patients with human immunodeficiency virus (HIV) infection, genital herpetic lesions may be extensive and tend to persist for longer periods; in addition, atypical hypertrophic, ulcerative, or pseudotumor forms have been reported, frequently showing resistance to acyclovir (ACV) treatment.” (opens the source at this quote in a new tab)

“All patients developed chronic, hypertrophic HSV-2 anogenital lesions with multilesional presentation in 7 cases and involvement of 2 anatomical sites in 6 of them.” (opens the source at this quote in a new tab)

“Detection of HSV-2 by culture and/or polymerase chain reaction was positive for all patients, with evidence for ACV-resistant strains in 6 of 8 cases. In addition, viral resistance to ACV was found only in HSV-2 isolated from ulcerative lesions, whereas purely pseudotumoral ones harbored sensitive strains.” (opens the source at this quote in a new tab)

“Hypertrophic herpes simplex (HHS) often has atypical presentations, such as a hypertrophic mass or ulcers, with chronic courses. This situation poses a diagnostic challenge and results in delayed treatment.” (opens the source at this quote in a new tab)

Necrotizing cutaneous lesions

“We report three cases of necrotizing cutaneous HSV infection in immunocompromised patients with underlying hematologic malignancies or prior chemoradiation, all presenting with atypical and refractory manifestations of the disease.” (opens the source at this quote in a new tab)

Pain

“Resistant HSV lesions can be painful, large, multifocal, and prolonged, leading to substantial patient discomfort.” (opens the source at this quote in a new tab)

“Acyclovir-resistant HSV infection is a rare clinical problem typically seen in the immunocompromised population, where it can cause painful protracted mucocutaneous disease associated with significant morbidity and mortality” (opens the source at this quote in a new tab)

“84.13 % (53/63, missing 47) complained of pain and multiple recurrences were found in 44.94 % (40/89, missing 21) cases.” (opens the source at this quote in a new tab)

“the intense and incapacitating discomfort that is characteristic of R/R HSV lesions” (opens the source at this quote in a new tab)

Lesion size

“The initial size of the HSV lesion was recorded in only 9 of 31 episodes. The median size reported was 81.0 mm2, but there was a wide range (4–4900 mm2).” (opens the source at this quote in a new tab)

Visceral, ocular, and disseminated disease

“Rarely, R/R HSV infections have manifested with systemic or invasive diseases such as encephalitis, pneumonitis, or hepatitis” (opens the source at this quote in a new tab)

“Fifteen patients had systemic involvement (respiratory tract, gastrointestinal tract, central nervous system, and cornea).” (opens the source at this quote in a new tab)

Site of system involvementRecipients, N (%) of 125
Respiratory“4 (3.2)”
Gastrointestinal (esophagitis)“6 (4.8)”
Central nervous system“1 (0.8)”

“Five of the patients had symptoms associated with HSV infection beyond the oral cavity, including the lung (three patients), eyes (two patients), esophagus (two patients), brain (one patient), vagina (one patient), and skin (one patient). HSV was cultured from the bloodstream of three patients and yielded positive results in all 3.” (opens the source at this quote in a new tab)

“Viremia (HSV DNAemia) was present in four (80%) cases, with clearance of viremia in response to antiviral therapy in only two.” (opens the source at this quote in a new tab)

“Seven patients were infected with resistant HSV-1 strains, including five solid organ transplant (SOT) recipients, one patient with pemphigus vulgaris receiving immunosuppressive therapy, and one immunocompetent individual.” (opens the source at this quote in a new tab)

“with three SOT recipients exhibiting multisite disease.” (opens the source at this quote in a new tab)

“Esophageal HSV disease is present in about 10% of patients with upper gastro-intestinal symptoms (II).” (opens the source at this quote in a new tab)

“Uncommon HSV disease manifestations are pneumonia (2-3% of patients in the absence of prophylaxis), hepatitis, meningitis, encephalitis, and bone marrow suppression (III).” (opens the source at this quote in a new tab)

“Other clinical syndromes associated with HSV, such as esophagitis, hepatitis, pneumonitis, and disseminated infection are relatively rare, and manifest mostly in immunocompromised hosts.” (opens the source at this quote in a new tab)

“However, viremia may herald visceral infection, particularly with multiple-organ involvement or disseminated disease, which can be associated with high mortality in severely immunosuppressed patients.” (opens the source at this quote in a new tab)

Onset during antiviral prophylaxis

“All patients were on HSV prophylaxis at the onset of the index episode” (opens the source at this quote in a new tab)

“Seventeen of the 18 patients were on valacyclovir or parenteral acyclovir for prophylaxis before diagnosis. The median duration of previous acyclovir exposure was 12 months (range: 2–28 months).” (opens the source at this quote in a new tab)

“All patients were on prophylactic acyclovir (or its prodrug, valacyclovir) prior to R/R HSV diagnosis. The median cumulative exposure to (val)acyclovir prior to presentation with R/R HSV was 30 months (range: 18-51 months).” (opens the source at this quote in a new tab)