Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Solid-organ Transplant Recipients on Continuous Veno-venous Hemodialysis.

BACKGROUND: Optimal valganciclovir dosing for cytomegalovirus (CMV) prophylaxis in solid-organ transplant (SOT) patients on continuous veno-venous hemodialysis (CVVHD) is not known. Ganciclovir trough concentrations ≥0.60 µg/mL have been suggested for CMV prophylaxis. This study was conducted to determine if valganciclovir 450 mg enterally every 24 hours achieves ganciclovir trough concentrations ≥0.60 µg/mL in patients on CVVHD. METHODS: This single-center, prospective, open-label, pharmacokinetic study included adult SOT patients admitted to an intensive care unit from March 2018 to June 2019 on CVVHD. All patients were receiving valganciclovir 450 mg enterally every 24 hours for CMV prophylaxis prior to enrollment. Each patient had a peak and trough sample drawn at steady state. RESULTS: Ten SOT patients were included in the study (6 liver, 1 simultaneous liver-kidney, 2 bilateral lung, 1 heart). The mean ± SD age was 51.8 ± 14.0 years, and average body mass index was 27 ± 6.9 kg/m2. Ganciclovir trough concentrations ranged from 0.31 to 3.16 µg/mL, and 80% of participants have trough concentrations ≥0.60 µg/mL. No patients had documented neutropenia while on valganciclovir and CVVHD; 60% of patients had significant thrombocytopenia. CONCLUSIONS: Valganciclovir 450 mg enterally every 24 hours achieved ganciclovir trough concentrations ≥0.60 µg/mL in most patients on CVVHD, similar to those reported with intravenous ganciclovir for prophylaxis in this population. Based on these data, valganciclovir may require dosing every 24 hours to achieve concentrations equivalent to ganciclovir. Neutropenia did not occur in the study period. Thrombocytopenia was common and likely multifactorial.

Hepatitis C-positive donor liver transplantation for hepatitis C seronegative recipients.

BACKGROUND: The opioid crisis has led to an increase in hepatitis C virus-positive donors in the past decade. Whereas historically hepatitis C seropositive organs were routinely discarded, the advent of direct-acting antiviral agents has notably expanded the utilization of organs from donors with hepatitis C. There has been growing experience with liver transplantation (LT) from hepatitis C seropositive donors to hepatitis C seropositive recipients. However, data remain limited on LT from hepatitis C seropositive or hepatitis C ribonucleic acid positive donors to hepatitis C seronegative recipients. METHODS: We performed a retrospective study of 26 hepatitis C seronegative recipients who received hepatitis C seropositive donor livers followed by preemptive antiviral therapy with direct-acting antiviral treatment at the Johns Hopkins Hospital Comprehensive Transplant Center from January 1, 2017, to August 31, 2019. RESULTS: Twenty-five of the 26 recipients are alive with proper graft function; 20 of them received livers from hepatitis C nucleic acid testing positive donors. All 12 recipients who completed their direct-acting antiviral courses and have reached sufficient follow-up for sustained virologic response have achieved sustained virologic response. Nine of our recipients have either completed direct-acting antiviral treatment without sufficient follow-up time for sustained virologic response or are undergoing direct-acting antiviral treatment. One patient is awaiting antiviral treatment initiation pending insurance approval. Of note, 11 of 12 patients with sustained virologic response received a hepatitis C nucleic acid testing positive donor liver. CONCLUSION: Hepatitis C seronegative patients who receive a hepatitis C seropositive or hepatitis C nucleic acid testing positive liver allograft can enjoy good short-term outcomes with hepatitis C cure following direct-acting antiviral treatment.

Access to direct-acting antivirals for hepatitis C-negative transplant recipients receiving organs from hepatitis C-viremic donors.

PURPOSE: A barrier to using organs from hepatitis C virus (HCV)-viremic donors is the high cost of direct-acting antivirals (DAAs) and concerns about access for recipients after transplantation. The purpose of this study was to evaluate access, cost, and timing for HCV DAAs following transplantation. METHODS: This was a single-center, retrospective study of HCV-negative adult transplant recipients from June 2017 to December 2019 who received grafts from HCV-viremic and/or HCV-seropositive individuals and became HCV viremic after transplantation. RESULTS: Between June 2017 and December 2019, there were 60 HCV-negative transplant recipients who became viremic after receiving grafts from HCV-viremic or HCV-seropositive donors. Thirty-eight patients met the inclusion criteria (n = 25 with liver transplants, n = 6 with lung transplants, n = 4 with simultaneous liver and kidney transplants, and n = 3 with kidney transplants). Of these patients, 23 had commercial insurance, 13 had Medicare, and 2 had Medicaid. All patients ultimately received insurance coverage for treatment; however, 36 (95%) required prior authorization and 9 (24%) required appeals to obtain insurance coverage. The median time from DAA prescription to insurance approval was 6 days. The median time from transplantation to start of treatment was 29 days (range, 0-84 days). Patients with Medicaid insurance had a significantly longer time to insurance approval (31.5 vs 6 days, P = 0.007). The average out-of-pocket cost to patients was less than $10 a month after patient assistance. All patients who completed treatment and 12-week follow-up after treatment achieved a sustained virologic response (n = 36). CONCLUSION: In this study, all HCV-negative recipients who developed HCV following transplantation had access to DAA therapy, with the majority starting treatment in the first month after transplantation.