Product information and disease description Place of product in therapy Disease description

Natural history, survival, and mortality

25 evidence topics · 16 sources

Clinical significance of resistant isolates by immune status

“Even when drug-resistant HSV is isolated from an immunocompetent patient, this virus, with rare exceptions, is cleared normally without adverse clinical outcome.” (opens the source at this quote in a new tab)
“Although drug-resistant HSV is more commonly isolated from immunocompromised patients (4%-7% of isolates) and is more likely to be clinically significant, the prevalence of drug-resistant HSV even among these patients, has been stable over the past 2 decades.” (opens the source at this quote in a new tab)

Seven-center United States cohort of 125 hematopoietic cell transplant recipients with refractory infection: design and follow-up

“This multicenter, retrospective study was conducted in 7 academic transplant centers in the United States.” (opens the source at this quote in a new tab)
“Refractory HSV cases were identified at each institution through review of institutional databases and electronic medical records for patients transplanted from 2009 through 2024.” (opens the source at this quote in a new tab)
“Adult (≥18 years) HCT with laboratory-confirmed mucocutaneous HSV infection (by polymerase chain reaction, viral culture, or immunohistochemistry) were eligible if they did not improve after ≥7 days of appropriately dosed anti-HSV therapy and received second line therapies or high-dose IV acyclovir unless at physicians' or patients' discretion they were not deemed candidates for second line therapy.” (opens the source at this quote in a new tab)
“Patients were followed up to 12 months from healing of the index HSV episode or until death or censoring, whichever occurred first.” (opens the source at this quote in a new tab)
“One hundred and twenty-five patients were analyzed. Ninety patients (72%) received HCT from January 2017 through December 2024 (contemporary cohort).” (opens the source at this quote in a new tab)
“The index HSV episode was diagnosed at a median of 101 days from HCT (Q1, Q3: 28, 351; minimum: −8, maximum 4116).” (opens the source at this quote in a new tab)

Seven-center United States cohort: complete healing, death on therapy, and time to healing

“Sixty-nine patients (55.2%) achieved our primary endpoint of complete healing. Forty patients (32.0%) died on therapy and 16 patients (12.8%) were censored before healing.” (opens the source at this quote in a new tab)
“Complete healing was achieved at a median of 38 days (Q1, Q3: 26, 65; range: 257) from the treatment index date” (opens the source at this quote in a new tab)
“The cumulative incidence of healing was 16.2% at day 28, 31.2% at day 42, and 53.4% at day 90 from the treatment index date.” (opens the source at this quote in a new tab)
“The most frequent observed healing time was approximately 30.8 days (dashed vertical line).” (opens the source at this quote in a new tab)
“Sixteen patients were censored before compete lesion healing, including 4 patients treated with pritelivir and 12 patients who discontinued anti-HSV treatment or were lost to follow up before healing.” (opens the source at this quote in a new tab)

Seven-center United States cohort: sensitivity analyses of time to healing

“Among patients excluding those treated with pritelivir (N = 121), the median time to healing was 38 days (Q1, Q3: 26, 65), with cumulative incidence of healing of 16.6% at day 28, 31.8% at day 42 and 53.9% at day 90.” (opens the source at this quote in a new tab)
“In the contemporary cohort (2017–2024; N = 90), the median time to healing was 37.5 days (Q1, Q3: 23, 63), with cumulative incidence of healing of 19.1% at day 28, 30.6% at day 42 and 52.6% at day 90.” (opens the source at this quote in a new tab)
“Among patients excluding the 14 patients who only received NUC therapy (N = 111), the median time to healing was 38 days (Q1, Q3: 26, 65), with cumulative incidence of 16.2% at day 28, 31.2% at day 42, and 53.4% at day 90.” (opens the source at this quote in a new tab)
“The median follow-up time among censored patients was 76 days (Q1, Q3: 35.5, 97.5), exceeding the median time to healing in the overall cohort (38 days; Q1, Q3: 26, 65), indicating that censored observations contributed substantial follow-up time and were unlikely to bias the estimates of time to healing.” (opens the source at this quote in a new tab)

Seven-center United States cohort: recurrence and death within 1 year after healing

“Sixty-nine patients achieved complete healing of the index HSV episodes. These patients were followed for HSV recurrence for up to 1 year after healing, death, or last follow up. At 1 year, 22 patients (31.9%) died and 27 patients (39.1%) had 1 or more recurrent HSV episode(s).” (opens the source at this quote in a new tab)
“The time to first recurrence was a median of 61 days (Q1, Q3: 29, 97; minimum, maximum: 10, 298). Of a total of 30 recurrent episodes, 7 had acyclovir resistance testing and acyclovir resistance was confirmed in 5 episodes.” (opens the source at this quote in a new tab)
“Recurrent HSV was defined as appearance of new, laboratory-confirmed HSV lesions >7 days after complete healing of the index episode until death or last follow up, up to 1 year from healing of the index refractory episode.” (opens the source at this quote in a new tab)

Seven-center United States cohort: authors' explanation of prolonged healing and recurrence

“Thus the prolonged time to healing may reflect not only persistent HSV replication but also impaired tissue repair associated with cytotoxic chemotherapy, mucositis, systemic corticosteroid exposure, and chronic graft-versus-host disease” (opens the source at this quote in a new tab)
“Thirty-nine percent of patients had recurrent HSV infections during the follow-up period, suggesting persistent immune deficits.” (opens the source at this quote in a new tab)

Five-center United States foscarnet cohort of 29 immunocompromised adults with 31 episodes: design and population

“This is a multicenter retrospective study in which each of 5 participating centers identified adult patients (aged ≥18 years) treated with foscarnet for HSV infection between 1 January 2012 and 31 December 2017.” (opens the source at this quote in a new tab)
“All subjects were immunocompromised, the majority of whom had a hematologic malignancy. No patient in the cohort had received a solid organ transplant, and 9 (31%) were PWH. Among the 19 patients (66%) with hematologic malignancy, 16 had undergone allogeneic HCT and 1 had undergone autologous HCT.” (opens the source at this quote in a new tab)
“Most episodes were due to resistant or refractory HSV; of the 18 HSV episodes where genotypic or phenotypic resistance testing was performed, 15 (83%) were confirmed as acyclovir resistant. Of the remaining 13 episodes where genotypic and phenotypic testing was not performed, refractory status could be determined in 10 episodes, of which 7 were refractory (70%).” (opens the source at this quote in a new tab)

Five-center United States foscarnet cohort: healing and time to healing

“Of the 31 episodes of HSV that were treated with foscarnet, 15 (48%) were reported to heal by the end of or after foscarnet therapy” (opens the source at this quote in a new tab)
“The median time to lesion healing was 38 days (range, 9–1088 days), which included healing even after foscarnet was stopped. Seven episodes (23%) healed within 28 days. Among the 16 episodes not reported as healing, 14 (45%) did not resolve after foscarnet therapy and information was not available after foscarnet therapy on 2 episodes.” (opens the source at this quote in a new tab)

Five-center United States foscarnet cohort: recurrence after healing

“Among the 15 episodes that resolved, 8 (53%) of these recurred at a median of 229 days (range, 31–1030 days).” (opens the source at this quote in a new tab)

Five-center United States foscarnet cohort: deaths

“Nine study subjects had 13 adverse events leading to death, none of which were considered to be related to foscarnet. Most adverse events leading to death were due to disorders of the respiratory system or infection.” (opens the source at this quote in a new tab)
“Adverse events leading to death occurred in 9 subjects, none of which were judged to be related to foscarnet therapy, but highlight the vulnerability of this patient population” (opens the source at this quote in a new tab)

Single-center United States cohort of 18 allogeneic transplant recipients with plaque-reduction-confirmed resistance: timing after transplant

“The median time from transplant to the first episode of acyclovir-resistant HSV infection was bimodal, with early presentation at a median of 10.5 days (IQR: 1–31 days) and late presentation at a median of 89.5 days (IQR: 41–735 days)” (opens the source at this quote in a new tab)
“Nine cases of acyclovir-resistant HSV infection (50%) occurred pre-engraftment, seven had a diagnosis of GvHD requiring systemic corticosteroids at least 1 month before diagnosis of the acyclovir-resistant HSV infection” (opens the source at this quote in a new tab)

Single-center United States transplant cohort: clinical response at 2 weeks and duration of therapy

“Clinical response to therapy was defined as total resolution or significant improvement of the HSV infection within 2 weeks of therapy.” (opens the source at this quote in a new tab)
“Five (28%) patients had a clinical response within two weeks of therapy, and 13 (72%) patients had slow or no clinical responses at 2 weeks (i.e., had no clinical improvement and/or had new lesions).” (opens the source at this quote in a new tab)
“Treatment with antiviral therapy was prolonged, reaching a median of 80 days in patients with good clinical responses and 100 days in patients with poor clinical responses.” (opens the source at this quote in a new tab)

Single-center United States transplant cohort: recurrence

“Recurrent HSV infection occurred in four patients (22%), all of whom had foscarnet-resistant HSV infection, an underlying diagnosis of GvHD, and were treated with parenteral or topical cidofovir therapy.” (opens the source at this quote in a new tab)

Single-center United States transplant cohort: 1-year mortality and causes of death

“Of the whole cohort, nine patients (50%) died within 1 year after HSV infection, and none of those nine had clinical responses. Causes of death included bacterial infections (n=4), heart failure (n=1), graft failure with diffuse alveolar hemorrhage (n=1), unknown causes (n=2), and HSV hepatitis with disseminated infection (n=1).” (opens the source at this quote in a new tab)
“There was one death related to resistant HSV infection in a patient with disseminated HSV infection and hepatitis.” (opens the source at this quote in a new tab)

Israeli hematology cohort of 18 participants with plaque-reduction-confirmed resistance: time to resistance diagnosis

“The time between treatment of the underlying disease and the detection of ACV resistance varied considerably across patients. The average duration was approximately 333 days (median 151.5 days).” (opens the source at this quote in a new tab)
“Seventeen of the 18 patients had undergone allogenic hematopoietic cell transplantation (HCT), and the remaining patient had undergone chemotherapy as monotherapy.” (opens the source at this quote in a new tab)

Israeli hematology cohort: mortality and survivor follow-up

“Eleven patients died within less than 6 months (median 3 months) from diagnosis of ACV resistance. While the direct cause of death was not recorded, oral lesions associated with HSV infection were documented in close proximity to the date of death in eight of these patients.” (opens the source at this quote in a new tab)
“They all died while on antiviral therapy.” (opens the source at this quote in a new tab)

Single-center United States series of 5 allogeneic transplant recipients classified by the consensus definitions: response and mortality

“The median time from transplant to R/R HSV was 642 days (range: 95-981 days).” (opens the source at this quote in a new tab)
“Protracted courses of antivirals (foscarnet followed by cidofovir, or foscarnet alone) were required, with a median duration of therapy of five weeks (range: two to nine weeks); and although clinical improvement was noted in all the patients, complete healing and resolution of the infection were achieved in none.” (opens the source at this quote in a new tab)
“Three-month mortality was 80%, and none of the patients survived 12 months from the R/R HSV diagnosis, although none of the deaths were directly attributed to the HSV infection. Causes of death included acute respiratory failure, procedure-related mortality, septic shock, and elective hospice with withdrawal of care.” (opens the source at this quote in a new tab)

Prospective Japanese transplant cohort of 268 recipients: 100-day death rates by shedding of acyclovir-resistant virus

“Herpes simplex virus type 1 was isolated in 39 of 268 (15%) HSCT patients within 100 days after transplantation. Acyclovir-resistant HSV-1 emerged in 11 of these 39 patients (28%).” (opens the source at this quote in a new tab)
“The 100-day death rates of HSCT patients without HSV-1 shedding, those with only ACV-sensitive HSV-1 shedding, and those with ACVr HSV-1 shedding were 31%, 39%, and 64%, respectively.” (opens the source at this quote in a new tab)
“Seven of the 11 patients died within 100 days after HSCT; death was attributable to infections other than HSV-1 (n = 4) or treatment-related complications (n = 3).” (opens the source at this quote in a new tab)
“Herpes simplex virus type 1, including ACVr HSV-1, shedding was associated with poorer outcome in HSCT patients, even if HSV disease did not always occur.” (opens the source at this quote in a new tab)

United Kingdom transplant series of 8 recipients with resistant HSV-1: recurrence, persistence, and death

“Foscarnet (FOS) treatment was initiated in all 8 patients (pending laboratory confirmation of ACV resistance) with some effect but associated with significant toxicity burden. Four patients presented again with recurrent HSV infection or no resolution. Three with recurrent HSV died from other causes while suffering from persistent oral HSV lesions.” (opens the source at this quote in a new tab)

French transplant series of 14 recipients with severe resistant HSV-1: response to foscarnet and cidofovir

“Fourteen cases of severe acyclovir-resistant herpes simplex virus type 1 (HSV-1) infection, 7 of which showed resistance to foscarnet, were diagnosed among 196 allogeneic stem cell transplant recipients within a 29-month period.” (opens the source at this quote in a new tab)
“In vitro resistance to acyclovir or foscarnet was associated with clinical failure of these drugs; however, in vitro susceptibility to foscarnet was associated with complete response in only 5 of 7 patients. No strain from any of the 7 patients was resistant in vitro to cidofovir; however, only 3 of 7 patients achieved complete response.” (opens the source at this quote in a new tab)

United Kingdom cohort of 75 allogeneic transplant recipients: clinical failure of acyclovir and foscarnet

“Sixteen patients developed HSV disease following transplantation.” (opens the source at this quote in a new tab)
“Seven patients did not respond to acyclovir, and 3 patients failed to respond to foscarnet.” (opens the source at this quote in a new tab)
“Clinical as well as in vitro resistance to antiviral drugs is common in patients with severe GVHD and is associated with a poor outcome.” (opens the source at this quote in a new tab)

Haploidentical transplant series: healing coincided with T-cell recovery

“HSV reactivation occurred in all 7 evaluable HSV-1- or HSV-2-seropositive patients, at a median of 40 days after transplantation.” (opens the source at this quote in a new tab)
“Second-line therapy produced only partial responses, and in vitro evidence of foscarnet resistance developed rapidly in all 3 patients treated with foscarnet. Healing of lesions coincided with T-cell recovery.” (opens the source at this quote in a new tab)
“Furthermore, immune reconstitution is necessary for eradication of infection.” (opens the source at this quote in a new tab)

German series of 6 transplant recipients with resistant HSV-1 stomatitis: mortality

“Among 214 consecutive HCT patients, 6 developed severe ACVr HSV-1 stomatitis (WHO grade III n = 1, WHO grade IV n = 5). All 6 patients suffered from relapse of acute myeloid leukemia (AML) after HCT.” (opens the source at this quote in a new tab)
“Five of the 6 patients died due to progression of leukemia. Only 1 patient survived.” (opens the source at this quote in a new tab)

French series including 5 solid organ transplant recipients: time to resistance detection and response to foscarnet

“The mean time to resistance detection in SOT recipients was 172 days post-transplantation, including three cases occurring despite antiviral prophylaxis.” (opens the source at this quote in a new tab)
“Consequently, four SOT recipients received second-line treatment with foscarnet, with clinical improvement of lesions observed in three cases, while treatment was discontinued in one due to nephrotoxicity.” (opens the source at this quote in a new tab)

Risk of dissemination from chronic mucocutaneous infection

“With few exceptions, CHSV and CVZV infections do not constitute significant risk factors for disseminated cutaneous or systemic infection.” (opens the source at this quote in a new tab)

“Disseminated HSV infection is rare, even in profoundly immunosuppressed people, such as recipients of hematopoietic stem cell transplant” (opens the source at this quote in a new tab)