Antiviral Prophylaxis Research Articles

İmmunsupresif Tedavi Alan Hastalarda HBV Reaktivasyonu ve Antiviral Profilaksinin Değerlendirilmesi

Aim: Patients with chronic hepatitis B and people with a history of hepatitis B (HBV) infection are at risk of HBV reactivation (HBVr) when they receive immunosuppressive therapy. In this study, we aimed to evaluate the hepatitis B serology, risk groups and antiviral prophylaxis of patients receiving various immunosuppressive therapies due to rheumatological diseases.
 Material and Method: The study included 375 patients over 18 years of age who received tumor necrosis factor-α (TNF-α) inhibitor, tyrosine kinase inhibitor, steroids, methotrexate or anti-CD20 antibodies due to rheumatic diseases in a training and research hospital between May 2022 and May 2023. Hepatitis B surface antigen (HbsAg), hepatitis B surface antibody (anti-Hbs), hepatitis B core protein antibody (anti-Hbc IgG) serologies, immunosuppressive therapies and oral antivirals were retrospectively analyzed.
 Results: The average age of the 375 patients included in the study was 43.77±13.07 years. 193 (51.5%) of the patients were male. 11 patients were HbsAg positive, 150 patients were anti-Hbs positive, 19 patients were isolated anti-Hbc IgG positive, and 79 patients were both anti-Hbs and anti-Hbc IgG positive. According to serological findings, 109 (29%) patients had HBV exposure. All three test results of 194 (51.7%) patients were negative. A total of 85 (22.7%) patients received oral antiviral prophylaxis due to the use of immunosuppressive agents. In terms of HBVr, 16.5% were evaluated as high risk, 75.3% as moderate risk, and 8.2% as low risk. Out of 85 patients 79 received entecavir, 5 reveived tenofovir disoproxil fumarate (TDF) and 1 received tenofovir alafenamide fumarate (TAF). The mean duration for the immunosuppressive therapy was 6.41±4.20 years. The mean duration of oral antiviral prophylaxis among patients was 1.02±1.72 years. HBVr was not observed in any of our patients.
 Conclusion: Before patients receive immunosuppressive therapy, hepatitis B serologies and prophylaxis indication should be evaluated firstly. In addition, as a preventive medicine activity, hepatitis B vaccinations of unvaccinated patients should be completed as quickly as possible.

Varicella zoster virus reactivation reported with isatuximab use

Isatuximab is a CD38-directed antibody indicated for the treatment of relapsed or refractory multiple myeloma. The Division of Pharmacovigilance at the U.S. Food and Drug Administration (FDA) reviewed case reports from postmarketing sources, including the FDA Adverse Event Reporting System (FAERS), PubMed, and Embase, to investigate a potential association between isatuximab and the risk of varicella zoster virus (VZV) reactivation. We identified 20 reports of which 15 met our case definition and causality criteria. All 15 patients (80% male, median age = 60 years) received isatuximab for a hematologic neoplasm; eight (53%) for previously untreated multiple myeloma. All cases described additional risk factors for VZV reactivation, including concomitant proteasome inhibitor and/or immunomodulatory drug (n = 10, 67%) use. Based on this postmarket analysis, the U.S. Prescribing Information for isatuximab was updated to include this new safety information, including recommendations for antiviral prophylaxis.

Use of next-generation sequencing to detect mutations associated with antiviral drug resistance in cytomegalovirus.

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality among immunocompromised hosts, including transplant recipients. Antiviral prophylaxis or treatment is used to reduce the incidence of CMV disease in this patient population; however, there is concern about increasing antiviral resistance. Detection of antiviral resistance in CMV was traditionally accomplished using Sanger sequencing of UL54 and UL97 genes, in which specific mutations may result in reduced antiviral activity. In this study, a novel next-generation sequencing (NGS) method was developed and validated to detect mutations in UL54/UL97 associated with antiviral resistance. Plasma samples (n = 27) submitted for antiviral resistance testing by Sanger sequencing were also analyzed using the NGS method. When compared to Sanger sequencing, the NGS assay demonstrated 100% (27/27) overall agreement for determining antiviral resistance/susceptibility and 88% (22/25) agreement at the level of resistance-associated mutations. The limit of detection of the NGS method was determined to be 500 IU/mL, and the lower threshold for detecting mutations associated with resistance was established at 15%. The NGS assay represents a novel laboratory tool that assists healthcare providers in treating patients who are infected with CMV harboring resistance-associated mutations and who may benefit from tailored antiviral therapy.

Extended duration letermovir in allogeneic hematopoietic stem cell transplant

ObjectivesDespite the use of antiviral prophylaxis in recipients of allogeneic hematopoietic cell transplants (HCT), cytomegalovirus (CMV) is a common clinically significant infection and is associated with significant morbidity and mortality in this patient population. Based on current approval, letermovir is initiated within 28 days following allogeneic HCT for CMV seropositive recipients and continued through 100 days post-transplant. However, it is unknown whether patients who receive extended duration CMV prophylaxis with letermovir would result in less CMV reactivation and reactivation compared to those who do not. This study aimed to evaluate the efficacy of letermovir prophylaxis in CMV seropositive patients when continued for greater than 100 days post-allogeneic stem cell transplant. MethodsA single-center retrospective chart review was conducted on recipients of allogeneic HCT from November 2017 to July 2021. Patients were eligible for inclusion if they were at least 18 years of age, received an allogeneic HCT, CMV seropositive, and initiated letermovir between days 0–28 post-transplant. The primary endpoint of this study is to compare rates of CMV reactivation in patients who stopped letermovir prophylaxis at 100 days post-transplant (standard duration group) versus those who continued letermovir prophylaxis past day 100 (extended duration group). ResultsA total of 87 patients met the eligibility criteria for inclusion. The median duration of letermovir prophylaxis was 78 days in the standard duration group versus and 132 days in the extended duration group. There were more CMV reactivations in the standard duration group versus the extended duration group, 28% versus 19% respectively. CMV pneumonitis was observed in one of the patients in the standard duration group. All-cause mortality at day 200 post-transplant was similar between the two groups. ConclusionThe results of this study suggest that extended duration letermovir prophylaxis may be associated with less CMV reactivation compared to the standard duration of prophylaxis.

Hepatitis B virus infection in patients presenting for immunosuppressive cancer therapy with and without underlying HIV infection

IntroductionReactivation of hepatitis B virus (HBV) infection induced by immunosuppressive cancer therapy is associated with fulminant liver disease and death. While national guidelines recommend HBV screening and antiviral prophylaxis for patients with cancer prior to initiating immunosuppressive therapy, compliance with these measures is unclear. This study characterized the burden of HBV infection among patients diagnosed with gynecological or dermatological cancers, with or without underlying HIV infection, before initiating immunosuppressive therapy. MethodsBetween 2016 – 2018, we recruited study patients from the Dr George Mukhari Academic Hospital in Tshwane, South Africa. Demographic (age, sex) and clinical data (HIV test results, HIV antiviral regimen, type of cancer) were recorded using a standardized data collection form. All participants were tested for HBV surface antigen (HBsAg), and antibodies to the surface (anti-HBs) and core antigens (anti-HBc). For detection of HBV DNA, a nested polymerase chain reaction was used to amplify polymerase gene fragments which were Sanger-sequenced and analyzed using bioinformatics software. All statistical analyses were performed using R version 4.1.0 (2021-05-18) and R studio version 2022.07.2. ResultsStudy participants were predominantly female (96.3%, 103/107) with a median (IQR) age of 50 (17.5) years. Cervical cancer was the most frequent cancer diagnosis (72%). Over half (52.3%; 56/107) of the participants were HIV positive and all but four (92.9%) on highly active antiretroviral therapy at the time of enrollment. The prevalence of chronic hepatitis B in the study population was 11.2% [95% CI:6.2-19.1], increasing to 14.3% [95% CI:6.8-26.8] in the HIV positive sub-population. The overall prevalence of occult HBV infection was 20% [95% CI:12.8-29.7], 57.9% [95% CI:33.97-78.9] of whom tested negative for all serological markers. Phylogenetic inference showed that all polymerase gene sequences generated in this study were sub-genotype A2. Mutational analysis did not reveal any drug resistance-associated amino acid variations in this study. ConclusionThese findings suggest that chronic and occult HBV infections are more prevalent among cancer patients with or without underlying HIV infection compared to what has previously been reported for the general South African population. This underscores the need to scale-up universal HBV serological and molecular screening with timely institution of prophylaxis prior to initiating immunosuppressive cancer therapy.

Hepatitis B reactivation is a rare event among patients with resolved infection undergoing anti-CD20 antibodies in monotherapy without antiviral prophylaxis: results from the HEBEM study

IntroductionProspective data on the risk of hepatitis B reactivation (HBVr) among patients with resolved HBV infection undergoing anti-CD20 antibodies monotherapy is scarce. We aimed to assess the risk of HBVr in patients with resolved HBV infection treated with rituximab or ocrelizumab in monotherapy for multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) without antiviral prophylaxis.MethodsHEBEM is a prospective study that included all consecutive adults HBsAg-negative/anti-HBc-positive who initiated anti-CD20 antibodies for MS or NMOSD at Cemcat. Inclusion criteria encompassed undetectable HBV-DNA, absence of other immunosuppressants or antiviral therapy. Every 6 months HBsAg, ALT and HBV-DNA were performed to rule out HBVr (defined by 2-log increase in HBV-DNA or seroconversion to HBsAg+).ResultsFrom August/2019 to August/2022, 540 subjects initiated anti-CD20 antibodies, 28 (5.2%) were anti-HBc-positive and were included. Twenty-two received rituximab and 6 ocrelizumab. The majority (89.3%) had previously received ≥ 1 immunomodulatory drug, with corticosteroids (82.1%) and interferon (42.9%) as the most common. At inclusion, all presented normal transaminases and undetectable HBV-DNA. Median anti-HBs levels were 105.5 mIU/mL (IQR 0–609). Median follow-up was 3.1 years (2.1–4.0). Median number of cycles of anti-CD20 antibodies was 6 (3–7), with a cumulative dose of 8.5 g (5.8–11.2) of rituximab and 3 g (1.8–3.8) of ocrelizumab. Neither cases of HBVr nor changes in anti-HBs titers were observed per 83.6 patient-years treated with monotherapy with anti-CD20 antibodies.ConclusionsIn this cohort of patients with MS or NMOSD and resolved HBV infection, anti-CD20 monotherapy was not associated with detectable risk of HBV reactivation despite the lack of antiviral prophylaxis.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era.

Hepatitis due to hepatitis B virus (HBV) reactivation can be serious and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver. The expression of these silent genomes is controlled by the immune system. Suppression or ablation of immune cells, most importantly B cells, may lead to reactivation of seemingly resolved HBV infection. Thus, all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Patients found to be positive for HBsAg should be given prophylactic antiviral therapy. For patients with resolved HBV infection, there are two approaches. The first is pre-emptive therapy guided by serial HBV DNA monitoring, and treatment with antiviral therapy as soon as HBV DNA becomes detectable. The second approach is prophylactic antiviral therapy, particularly for patients receiving high-risk therapy, especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation. Entecavir and tenofovir are the preferred antiviral choices. Many new effective therapies for hematological malignancies have been introduced in the past decade, for example, chimeric antigen receptor (CAR)-T cell therapy, novel monoclonal antibodies, bispecific antibody drug conjugates, and small molecule inhibitors, which may be associated with HBV reactivation. Although there is limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, including Bruton's tyrosine kinase inhibitors, B-cell lymphoma 2 inhibitors, and CAR-T cell therapy. Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.

Herpes Zoster Infections in Solid-Organ Transplant Recipients.

Herpes zoster infections can be complicated and mortal in solid-organ transplant recipients. In our study, we investigated herpes zoster infections in solid-organ transplant recipients. UntilJune 2022, our center has performed 3342 kidney, 708 liver, and 148 heart transplants.Herpes zosterinfections were investigated in 1050 adult solid-organ transplant recipients from January 1, 2011, to June 31, 2022. We studied 44 patients diagnosed with herpes zoster infections. Of the 44 patients with herpes zoster, 32 had kidney, 7 had heart, and 5 had liver transplant procedures. Crude incidence rate was 5.2%.,with 9.7% being heart, 5.1% being kidney, and 3.9% being liver transplant recipients; 72.7% were male patients. The median age was 47.5 years, and 61% of patients were aged >45 years. Postherpetic neuralgia was significantly higher in patients older than 45 years (P = .006). The median duration to infection posttransplant was 16.5 months. The dermatomes of patients were 43.2% thoracic. Sacral dermatome involvement was significantly higher in heart transplant patients than in other transplant recipients (P = .015). We reviewed specific findings of the Tzanck test in 36.4% of the patients. There was concomitant infection in 15.9% of the patients, and 6.8% had pneumonia. Acute neuritis was more common in kidney transplant recipients (65.6%). The mean duration of acute neuritis/neuralgia was longest in liver transplant recipients (13.5 months; P = .047). Postherpetic neuralgia was detected as high as 24%. Early specific and supportive treatmentis important for transplant recipients with herpes zoster infections. Appropriate antiviral prophylaxis regimens and vaccination strategies for varicella zoster (chickenpox) and herpes zoster infections should be implemented in the vaccination schedule of solidorgan transplant candidates to prevent herpes zoster infections and complications.

Cytomegalovirus Disease as a Risk Factor for Invasive Fungal Infections in Liver Transplant Recipients under Targeted Antiviral and Antimycotic Prophylaxis.

We retrospectively analyzed the medical records of 214 adult liver transplant recipients (LTRs). Universal antiviral prophylaxis was utilized in recipients with CMV mismatch; intermediate- and low-risk patients received pre-emptive treatment. Six percent of patients developed CMV disease independent of their serostatus. The occurrence of CMV disease was associated with elevated virus load and increased incidence of leucopenia and IFIs. Furthermore, CMV disease was associated with higher one-year mortality and increased relapse rates within the first year of OLT. CMV disease causes significant morbidity and mortality in LTRs, directly affecting transplant outcomes. Due to the increased risk of IFIs, antifungal prophylaxis for CMV disease may be appropriate. Postoperative CMV monitoring should be considered after massive transfusion, even in low-risk serostatus constellations. In case of biliary complications, biliary CMV monitoring may be appropriate in the case of CMV-DNA blood-negative patients.

Hepatitis B virus reactivation in seronegative occult hepatitis B patient receiving ibrutinib therapy

BackgroundIbrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor approved for the treatment for several mature B-cell malignancies. Reactivation of hepatitis B virus (HBV) is a well-described complication in patients with chronic HBV infection or prior HBV exposure undergoing cytotoxic or immunosuppressive chemotherapy for hematologic malignancies. This phenomenon has been frequently reported with rituximab. However, published data on the risk of HBV reactivation induced by ibrutinib are scarce. Cases of HBV reactivation in hematologic patients receiving ibrutinib therapy have recently been described, but limited only to overt hepatitis B patients or seropositive occult hepatitis B patients.Case presentationWe report the first case of HBV reactivation during ibrutinib treatment in an asymptomatic 82-year-old woman with seronegative occult hepatitis B patient (i.e., negative for HBsAg, anti-HBc and anti-HBs). Four months after ibrutinib treatment, her liver function test (LFT) was deranged, with seroconversion to HBsAg positivity. Serum hepatitis B virus DNA was quantified to be 1.92 × 108 IU/ml. Antiviral treatment was initiated, and viral load was gradually suppressed with improvement in LFT.ConclusionsOur case illustrated that in populations with a high incidence of HBV exposure, systematic screening for HBV exposure is essential prior to ibrutinib treatment, followed by serial monitoring of serologic and molecular markers of hepatitis B. There is a need for an international consensus to support the recommendation of antiviral prophylaxis against HBV reactivation in patients using ibrutinib.

Utilization of hepatitis B surface antigen-positive donors in liver transplantation for recipients with hepatocellular carcinoma: a retrospective and propensity score matching analysis.

The use of extended criteria donor (ECD) grafts such as donor with infection of hepatitis B virus (HBV) is a potential solution for organ shortage. In this study, we aimed to evaluate the safety and long-term survival of utilization of hepatitis B surface antigen-positive (HBsAg+) donor livers in HCC patients using propensity score matching (PSM) analysis. Forty-eight donors with HBsAg-positive and 279 donors with HBsAg-negative were transplanted and enrolled in this study. PSM analysis were used to eliminate selection bias. Perioperative data and survival were collected and analyzed. PSM generated 44 patient pairs. When comparing intra- and post-operative data, no significant difference was found between groups (P>0.05). Patients with a HBsAg-positive donor had significantly worse progression-free survival (1-year: 65.9% vs. 90.9%; 3-year: 18.1% vs. 70.4%, P=0.0060) and overall survival (1-year: 84.1% and 95.4%; 3-year: 27.2% vs. 79.5%, P=0.0039). In multivariate analysis, donor HBsAg-positivity was an independent risk factor for survival and occurrence (P=0.005 and 0.025, respectively). In conclusion, with adequate antiviral prophylaxis and treatment, utilization of HBsAg positive liver grafts did not increase the incidence of early-stage complications. However, patient with an HBsAg-positive graft had poorer progression-free survival and overall survival.

A Systematic Review and Meta-analysis of Optimized CMV Preemptive Therapy and Antiviral Prophylaxis for CMV Disease Prevention in CMV High-Risk (D+R-) Kidney Transplant Recipients.

We conducted a systematic review and meta-analysis of PET with weekly CMV polymerase chain reaction monitoring for ≥3 mo and UP with 6 mo of valganciclovir. PubMed and Embase databases were reviewed from January 1, 2010, to April 1, 2022. Risk of bias was assessed with 3 instruments (Cochrane RoB, Cochrane RoBINS-I, and an instrument for assessing risk in observational studies). The primary outcome was CMV disease incidence by 1-y posttransplant. Secondary outcomes by 1-y were graft loss, acute allograft rejection, and mortality. Results were synthesized using generalized linear mixed model meta-analysis. PET studies were stratified into low-threshold (LT) and high-threshold (HT) PET based on the viral load threshold for initiation of antiviral therapy. Twenty-five studies met inclusion criteria (6 PET, 19 UP). CMV disease incidence was significantly higher in HT (0.30 [95% confidence interval (CI), 0.22-0.39]) versus LT PET (0.06 [95% CI, 0.03-0.12]). LT PET was associated with a significantly lower CMV disease incidence (0.06 [95% CI, 0.03-0.12]) versus UP (0.21 [95% CI, 0.17-0.27]). Incidence of graft loss, acute allograft rejection, or mortality was not significantly different between LT PET and UP (P > 0.05 for all comparisons). Receipt of lymphocyte-depleting antibodies was not associated with a significant difference in CMV disease incidence (odds ratio = 1.34 [95% CI, 0.80-2.25]). LT PET is associated with a significantly lower incidence of CMV disease compared to UP with similar rates of other clinical outcomes. These findings provide rationale and preliminary data for a randomized superiority trial of optimized LT-PET versus UP in donor seropositive recipient seronegative kidney transplant recipients.

Rapid Detection of Influenza Outbreaks in Long-Term Care Facilities Reduces Emergency Room Visits and Hospitalization: A Randomized Trial

ObjectivesTo assess whether the use of rapid influenza diagnostic tests (RIDTs) for long-term care facility (LTCF) residents with acute respiratory infection is associated with increased antiviral use and decreased health care utilization. DesignNonblinded, pragmatic, randomized controlled trial evaluating a 2-part intervention with modified case identification criteria and nursing staff–initiated collection of nasal swab specimen for on-site RIDT. Setting and ParticipantsResidents of 20 LTCFs in Wisconsin matched by bed capacity and geographic location and then randomized. MethodsPrimary outcome measures, expressed as events per 1000 resident-weeks, included antiviral treatment courses, antiviral prophylaxis courses, total emergency department (ED) visits, ED visits for respiratory illness, total hospitalizations, hospitalizations for respiratory illness, hospital length of stay, total deaths, and deaths due to respiratory illness over 3 influenza seasons. ResultsOseltamivir use for prophylaxis was higher at intervention LTCFs [2.6 vs 1.9 courses per 1000 person-weeks; rate ratio (RR) 1.38, 95% CI 1.24-1.54; P < .001]; rates of oseltamivir use for influenza treatment were not different. Rates of total ED visits (7.6 vs 9.8/1000 person-weeks; RR 0.78, 95% CI 0.64-0.92; P = .004), total hospitalizations (8.6 vs 11.0/1000 person-weeks; RR 0.79, 95% CI 0.67-0.93; P = .004), and hospital length of stay (35.6 days vs 55.5 days/1000 person-weeks; RR 0.64, 95% CI 0.0.59-0.69; P < .001) were lower at intervention as compared to control LTCFs. No significant differences were noted for respiratory-related ED visits or hospitalizations or in rates for all-cause or respiratory-associated mortality. Conclusions and ImplicationsThe use of low threshold criteria to trigger nursing staff–initiated testing for influenza with RIDT resulted in increased prophylactic use of oseltamivir. There were significant reductions in the rates of all-cause ED visits (22% decline), hospitalizations (21% decline), and hospital length of stay (36% decline) across 3 combined influenza seasons. No significant differences were noted in respiratory-associated and all-cause deaths between intervention and control sites.

Informing a target product profile for rapid tests to identify HBV-infected pregnant women with high viral loads: a discrete choice experiment with African healthcare workers

BackgroundElimination of mother-to-child transmission of hepatitis B virus (HBV) requires infant immunoprophylaxis and antiviral prophylaxis for pregnant women with high viral loads. Since real-time polymerase chain reaction (RT-PCR), a gold standard for assessing antiviral eligibility, is neither accessible nor affordable for women living in low-income and middle-income countries (LMICs), rapid diagnostic tests (RDTs) detecting alternative HBV markers may be needed. To inform future development of the target product profile (TPP) for RDTs to identify highly viremic women, we used a discrete choice experiment (DCE) and elicited preference and trade-off of healthcare workers (HCW) in Africa between the following four attributes of fictional RDTs: price, time-to-result, diagnostic sensitivity, and specificity.MethodsThrough an online questionnaire survey, we asked participants to indicate their preferred test from a set of two RDTs in seven choice tasks with varying levels of the four attributes. We used mixed multinomial logit models to quantify the utility gain or loss generated by each attribute. We attempted to define minimal and optimal criteria for test attributes that can satisfy ≥ 70% and ≥ 90% of HCWs, respectively, as an alternative to RT-PCR.ResultsA total of 555 HCWs from 41 African countries participated. Increases in sensitivity and specificity generated significant utility and increases in cost and time-to-result generated significant disutility. The size of the coefficients for the highest attribute levels relative to the reference levels were in the following order: sensitivity (β = 3.749), cost (β = -2.550), specificity (β = 1.134), and time-to-result (β = -0.284). Doctors cared most about test sensitivity, while public health practitioners cared about cost and midwives about time-to-result. For an RDT with 95% specificity, costing 1 US$, and yielding results in 20 min, the minimally acceptable test sensitivity would be 82.5% and the optimally acceptable sensitivity would be 87.5%.ConclusionsAfrican HCWs would prefer an RDT with the following order of priority: higher sensitivity, lower cost, higher specificity, and shorter time-to-result. The development and optimization of RDTs that can meet the criteria are urgently needed to scale up the prevention of HBV mother-to-child transmission in LMICs.

The risk of mother-to-child transmission of hepatitis B virus infection in Ethiopia: A systematic review and meta-analysis.

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is a predominant route of infection for children in Ethiopia. No study has so far reported a nationwide estimate of the risk of MTCT of HBV. We conducted a meta-analysis of surveys and estimated the pooled risk of MTCT of HBV in the context of human immunodeficiency virus (HIV) infection. We searched PubMed, EMBASE, Web of Science, Africa Index Medicus, and Google Scholar databases for peer-reviewed articles. The pooled risk of MTCT of HBV was estimated using the DerSimonian-Laird technique with logit transformed proportions and statistical heterogeneity was estimated using I2 statistic, which was explored by subgroup and meta-regression analyses. The overall pooled risk of MTCT of HBV in Ethiopia was 25.5% (95% CI, 13.4%-42.9%). In women without HIV infection, the risk of MTCT of HBV was 20.7% (95% CI 2.8%-70.4%), and 32.2% (95% CI 28.1%-36.7%) in women with HIV infection. After excluding the outlier study, the risk of MTCT of HBV in studies that included only HIV negative women was 9.4% (95% CI, 5.1%-16.6%). The risk of MTCT of HBV in Ethiopia widely varied by HBV/HIV coinfection. A sustainable control and elimination of HBV in Ethiopia requires improved access to birth-dose HBV vaccine and implement immunoglobulin prophylaxis for exposed infants. Given the limited health resources in Ethiopia, prenatal antiviral prophylaxis integrated with antenatal care may be a cost-effective approach to significantly reduce the risk of MTCT of HBV.

Single-cell analysis reveals HBV-specific PD-1+CD8+ TRM cells in tumor borders are associated with HBV-related hepatic damage and fibrosis in HCC patients

Immune checkpoint blockade (ICB) treatment of hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) infection may activate viral-specific T cells to attack HBV infected hepatocytes and thus induce immune-related liver injury. Therefore, it is important to deeply understand the impacts of HBV infection on HCC immune microenvironment in order to better design effective immunotherapies for HBV+ (HBV infected) HCC patients. Here, We performed cytometry by time-of-flight (CyTOF) analyses to characterize the distinct immune compositions of HCC tumors, tumor borders, and their associations with HCC/HBV related clinical characteristics. We identified 31 distinct immune clusters and found significant associations between immune signatures with clinicopathological features of HCC. We further revealed the HBV infection had more effects on shaping immune compositions in tumor borders than in tumors, with the significant enrichment of HBV-specific PD-1+CD8+ tissue-resident memory T (TRM) cells in tumor borders of HBV+ patients. We confirmed this subset with a more exhausted phenotype and respond more actively under anti-PD-L1 treatment, suggesting its involvement in immune-related liver injury induced by ICB treatment to HBV+ HCC patients. Our study shows it may be necessary to consider antiviral prophylaxis for HBV+ HCC patients receiving ICB treatment.

#5721 HEPATITIS B VIRUS REACTIVATION IN KIDNEY TRANSPLANT RECIPIENTS TREATED WITH BELATACEPT

Abstract Background and Aims Hepatitis B virus (HBV) reactivation in kidney transplant recipients may be associated with liver failure and graft loss, especially in anti-HBc antibody (HBcAb)-positive HBs antigen (HBsAg)-negative patients. Belatacept, a selective costimulation blocker, has been used in kidney transplantation for some time and has been associated with reactivation of other viruses as BK or CMV. However, there are few data on HBV reactivation among kidney recipients treated with belatacept. Method We performed a retrospective study in two French kidney transplantation centres including all transplant recipients receiving belatacept. Among HBcAb-positive patients, we analyzed HBV reactivation rate, outcomes and risks factors. Results 135 patients treated with belatacept were included, and 32 were HBcAb-positive. Seven patients reactivated HBV (21.9% of HBcAb-positive patients), including 5 HBsAg-negative patients (16.7%); reactivation occurred 54.8 (± 70.9) months after transplantation. There was no significant difference in survival between patients that reactivated HBV and patients that did not: 5-year patient survival of 100% (28.6; 100) and 83.4% (67.6; 100), respectively (p = 0.363) and 5-year graft survival of 100% (28.6; 100) and 79.8% (61.7; 100), respectively (p = 0.335). No factor, including HBsAb positivity and antiviral prophylaxis, was statistically associated with the risk of HBV reactivation. Conclusion Compared to the few studies that exist in this area, the HBV reactivation rate was high in patients treated with belatacept in our study. Our findings suggest that systematic antiviral prophylaxis for anti-HBc antibody (HBcAb)-positive HBs antigen (HBsAg)-negative patients should be considered and that there should be close monitoring of HBV serology and viral load in these patients to detect early HBV reactivation.

Virus-Specific T Cells From Cryopreserved Blood During an Emergent Virus Outbreak for a Potential Off-the-Shelf Therapy

During the first outbreak of an emergent virus, methods need to be developed to rapidly establish suitable therapies for patients with high risk of severe disease caused by the pathogen. Considering the importance of the T-cell response in controlling viral infections, adoptive cell therapy with virus-specific T cells has been used as a safe and effective antiviral prophylaxis and treatment for immunocompromised patients. The main objective of this study was to establish an effective and safe method to cryostore whole blood as starting material and to adapt a T-cell activation and expansion protocol to generate an off-the-shelf antiviral therapeutic option. Additionally, we studied how memory T-cell phenotype, clonality based on T-cell receptor, and antigen specificity could condition characteristics of the final expanded T-cell product. Twenty-nine healthy blood donors were selected from a database of convalescent plasma donors with a confirmed history of SARS-CoV-2 infection. Blood was processed using a fully automated, clinical-grade, and 2-step closed system. Eight cryopreserved bags were advanced to the second phase of the protocol to obtain purified mononucleated cells. We adapted the T-cell activation and expansion protocol, without specialized antigen-presenting cells or presenting molecular structures, in a G-Rex culture system with IL-2, IL-7, and IL-15 cytokine stimulation. The adapted protocol successfully activated and expanded virus-specific T cells to generate a T-cell therapeutic product. We observed no major impact of post-symptom onset time of donation on the initial memory T-cell phenotype or clonotypes resulting in minor differences in the final expanded T-cell product. We showed that antigen competition in the expansion of T-cell clones affected the T-cell clonality based on the T-cell receptor β repertoire. We demonstrated that good manufacturing practice of blood preprocessing and cryopreserving is a successful procedure to obtain an initial cell source able to activate and expand without a specialized antigen-presenting agent. Our 2-step blood processing allowed recruitment of the cell donors independently of the expansion cell protocol timing, facilitating donor, staff, and facility needs. Moreover, the resulting virus-specific T cells could be also banked for further use, notably maintaining viability and antigen specificity after cryopreservation.

Immune checkpoint inhibitors use and the incidence of hepatitis B virus reactivation or immune-related hepatitis in non-small cell lung cancer patients with chronic hepatitis B.

9086 Background: The safety and efficacy of immune-checkpoint inhibitors (ICIs) has not been thoroughly investigated in non-small cell lung cancer (NSCLC) patients with chronic hepatitis B (CHB) or occult hepatitis B infection (OBI). We analyzed incidence of hepatitis B virus (HBV) reactivation, immune-related hepatitis and jaundice in NSCLC patients treated with ICIs according to HBV DNA and hepatitis B serologic markers in real-world setting. Methods: A total of 1,277, consecutive NSCLC patients treated with ICIs from January 2015 to December 2020 at the Samsung Medical Center, Seoul, Korea were analyzed. Among them, 52 patients were hepatitis B surface antigen (+) (Group A, CHB), 759 patients were HBsAg (-)/anti-HBc IgG (+) (Group B, OBI), and 466 patients were HBsAg (-)/anti-HBc IgG (-) (Group C). Among 52 patients with CHB, 38 patients (73.1%) were receiving antiviral therapy. Primary endpoint was HBV reactivation, immune-related hepatitis and jaundice. Secondary endpoints include other immune-related adverse events, objective response rate, progression free survival (PFS) and overall survival (OS). Results: HBV reactivation was observed in two patients (0.2%) which was exclusively observed in Group A (CHB). Among CHB patients who were not receiving antiviral therapy, HBV reactivation was observed for 14.3% (2/14 patients). Incidence of immune-related hepatitis were 21.2%, 30.3% and 30.5% for Group A, Group B and Group C (p &gt; 0.05), respectively, and incidence of immune-related of jaundice was 3.8%, 4.0% and 2.8% for Group A, Group B and Group C (p &gt; 0.05), respectively. Incidence of ≥ grade 3 other immune-related adverse events, objective response rate, PFS, and OS were comparable among three group (p &gt; 0.05 for all comparison). Conclusions: In this large, real-world cohort study, safety and efficacy of ICIs were comparable in patients with CHB or OBI, suggesting similar outcomes can be expected with ICIs in patients with CHB or OBI. HBV reactivation was observed in patients with CHB without antiviral therapy indicating antiviral prophylaxis might be required for them. For patients with OBI, risk of HBV reactivation was null.

FRI-191 - What is the most effective strategy to identify HBV-infected pregnant women eligible for antiviral prophylaxis in Burkina Faso? A modelling study on different testing strategies

FRI-191 - What is the most effective strategy to identify HBV-infected pregnant women eligible for antiviral prophylaxis in Burkina Faso? A modelling study on different testing strategies