Evaluation of low dose famciclovir as herpes simplex virus and varicella zoster virus prophylaxis in cytomegalovirus low-risk solid organ transplant recipients.

OBJECTIVE: Famciclovir is a recommended option for herpes simplex virus (HSV) and varicella-zoster virus (VZV) prophylaxis in cytomegalovirus (CMV) low-risk solid organ transplant (SOT) recipients in current guidelines; however there is currently no data evaluating its use in SOT recipients. We conducted a multicenter provider survey on antiviral prophylaxis in CMV low-risk SOT recipients and evaluated the efficacy and safety of once daily famciclovir antiviral prophylaxis. METHODS: Two-part analysis consisting of a national provider survey and a retrospective chart review of 78 kidney transplant recipients at a single institution. RESULTS: Providers from 45 transplant centers within the United States responded to the survey. Across all organs, acyclovir 400 mg twice daily was utilized by the majority of respondents (70.4%), with most using prophylaxis for a duration of 3 months (68.8%). No respondents reported use of famciclovir at their institution. In the retrospective review there were no documented cases of HSV/VZV/CMV infection during the 3 months of famciclovir prophylaxis, and only one patient (1.3%) later developed VZV infection at 12 months post-transplant. One patient (1.3%) required premature discontinuation of famciclovir due to concern for acute interstitial nephritis. CONCLUSION: Nationwide, the most common antiviral prophylaxis used in CMV low-risk SOT recipients is acyclovir 400 mg twice daily. Among patients receiving once daily famciclovir for CMV low-risk antiviral prophylaxis, there was no HSV/VZV/CMV infection while on prophylaxis. Once daily famciclovir may provide an effective and convenient once daily dosing regimen for antiviral prophylaxis in CMV low-risk SOT recipients.

Immediate administration of antiviral therapy after transplantation of hepatitis C-infected livers into uninfected recipients: Implications for therapeutic planning.

The practice of transplanting hepatitis C (HCV)-infected livers into HCV-uninfected recipients has not previously been recommended in transplant guidelines, in part because of concerns over uncontrolled HCV infection of the allograft. Direct-acting antivirals (DAAs) provide an opportunity to treat donor-derived HCV-infection and should be administered early in the posttransplant period. However, evidence on the safety and efficacy of an immediate DAA treatment approach, including how to manage logistical barriers surrounding timely DAA procurement, are required prior to broader use of HCV-positive donor organs. We report the results of a trial in which 14 HCV-negative patients underwent successful liver transplantation from HCV-positive donors. Nine patients received viremic (nucleic acid testing [NAT]-positive) livers and started a 12-week course of oral glecaprevir-pibrentasvir within 5 days of transplant. Five patients received livers from HCV antibody-positive nonviremic donors and were followed using a reactive approach. Survival in NAT-positive recipients is 100% at a median follow-up of 46 weeks. An immediate treatment approach for HCV NAT-positive liver transplantation into uninfected recipients is safe and efficacious. Securing payer approval for DAAs early in the posttransplant course could enable need-based allocation of HCV-positive donor organs irrespective of candidate HCV status, while averting chronic HCV allograft infection.

Pre-emptive pangenotypic direct acting antiviral therapy in donor HCV-positive to recipient HCV-negative heart transplantation: an open-label study.

BACKGROUND: Low donor heart availability underscores the need to identify all potentially transplantable organs. We sought to determine whether pre-emptive administration of pangenotypic direct-acting antiviral therapy can safely prevent the development of chronic hepatitis C virus (HCV) infection in uninfected recipients of HCV-infected donor hearts. METHODS: Patients were recruited for this an open-label, single-centre, proof-of-concept study from Nov 1, 2017, to Nov 30, 2018. Following enrolment, the recipient's status on the heart transplantation waiting list was updated to reflect a willingness to accept either an HCV-positive or HCV-negative heart donor. Patients who underwent transplantation with a viraemic donor heart, as determined by nucleic acid testing (NAT), received pre-emptive oral glecaprevir-pibrentasvir before transport to the operating room followed by an 8-week course of glecaprevir-pibrentasvir after transplantation. Patients receiving HCV antibody-positive donor hearts without detectable circulating HCV RNA were followed using a reactive approach and started glecaprevir-pibrentasvir only if they developed viraemia. The primary outcome was achievement of sustained virological response 12 weeks after completion of glecaprevir-pibrentasvir therapy (SVR12). Patients were followed from study enrolment to 1 year after transplantation. This is an interim analysis, initiated after all enrolled patients reached the primary outcome. Results reflect data from Nov 1, 2017, to May 30, 2019. This trial is registered with ClinicalTrials.gov, number NCT03208244. FINDINGS: 55 patients were assessed for eligibility and 52 consented to enrolment. 25 patients underwent heart transplantation with HCV-positive donor hearts (20 NAT-positive, five NAT-negative), three of whom underwent simultaneous heart-kidney transplantation. All 20 recipients of NAT-positive hearts tolerated glecaprevir-pibrentasvir and showed rapid viral suppression (median time to clearance 3·5 days, IQR 0·0-8·3), with the subsequent achievement of SVR12 by all 20. The five recipients of NAT-negative grafts did not become viraemic. Median pre-transplant waiting time for patients following enrolment in the HCV protocol was 20 days (IQR 8-57). Patient and allograft survival were 100% at a median follow-up of 10·7 months (range 6·5-18·0). INTERPRETATION: Pre-emptive administration of glecaprevir-pibrentasvir therapy results in expedited organ transplantation, rapid HCV suppression, prevention of chronic HCV infection, and excellent early allograft function in patients receiving HCV-infected donor hearts. Long-term outcomes are not yet known. FUNDING: American Association for the Study of Liver Diseases, National Institutes of Health, and the Massachusetts General Hospital.

Utilization of increased risk for transmission of infectious disease donor organs in solid organ transplantation: Retrospective analysis of disease transmission and safety.

The inadequate supply of transplantable organs necessitates new approaches to organ availability. Serologies and nucleic acid testing (NAT) for hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) are used in microbiologic screening of potential organ donors. Organs from donors considered at "high risk" (Centers for Disease Control and Prevention, CDC 1994) or "increased risk" (U.S. Public Health Service, PHS 2013) for transmission of viral infection to recipients may provide an expanded source of organs for transplantation. We review a single-center experience with 257 adult organ recipients of organs from donors meeting either CDC 1994 or PHS 2013 risk criteria between 2011 and 2016. Tracking these transplants required modification of the Transplant Center electronic database to identify all recipients of increased-risk donor (IRD) organs, documentation of informed consent, and microbiologic testing data. No transmissions of HIV, HBV, or HCV were identified by NAT or clinically. Nine patients developed positive serologic assays for one of the tested viruses; all recipients were retested and remain negative by NAT. Notably, post-transplant HBV core serologies reverted to negative on re-testing; these positive serologies are likely false positives caused by receipt of blood products. Use of IRD organs can be performed safely with appropriate informed consent and rigorous pre- and post-transplant microbiological testing.

Attitudes and Perceptions of the Human Papillomavirus Vaccine in Caribbean and African American Adolescent boys and Their Parents.

STUDY OBJECTIVE: Human papillomavirus (HPV) is the most common sexually transmitted infection in the world. The prevalence of HPV in men ranges from 20% to 65% and is high at all ages. HPV vaccine has high efficacy in preventing HPV infection, cervical cancer, and genital warts. The study objectives were to describe attitudes and perceptions toward acceptability of HPV vaccination among inner-city Caribbean and African American adolescent boys and their parents and to identify and discuss correlates that may be associated with these factors. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional survey, administered in a general adolescent medicine clinic. Participants were recruited from a convenience sample of adolescent boys aged 13 to 19 years currently under care at an adolescent medicine clinic. RESULTS: Responses of 101 adolescent boys and 35 parents were analyzed. Consistent condom use was associated with less interest in HPV vaccination; those reporting consistent condom use had an 88% decreased odds of being interested in HPV vaccination compared with those reporting inconsistent condom uses. Interest in receiving the HPV vaccine was significantly associated with having increased numbers of sexual partners. CONCLUSION: Overall, most adolescent males (65%) were interested in receiving the HPV vaccine and a majority believed their parents would allow the vaccination (77.2%). Parental knowledge that the majority of cervical and rectal cancers are caused by HPV increased the odds of parents believing their sons need HPV vaccination; however, it is not statistically significant.