1748. Incidence of Cytomegalovirus Disease and Viral Replication Kinetics in Intermediate Risk Liver Transplant Recipients Managed According to a Preemtive Therapy Algortihm

Background Cytomegalovirus (CMV) is an important opportunistic pathogen in liver transplant recipients (LTR). Risk of invasive disease is determined by CMV donor/recipient (D/R) serostatus, immunosuppression, and use of antiviral prophylaxis. Viral replication kinetics that can predict the development of CMV disease in transplant recipients are a high maximal viral load (VL) and a fast replication velocity. At our institution LTR at intermediate risk for CMV disease (CMV D/R+) are managed following a preemptive therapy algorithm (the pre-established cutoff for treatment initiation is 4,000 IU/mL). The primary endpoint of this study was to determine the incidence of early CMV disease in CMV D/R+ LTR. Secondary endpoints were to calculate the period of maximal VL and viral kinetic parameters. Methods We performed a retrospective observational study of CMV D/R+ LTR. Patients were followed for 6 months after transplantation. We calculated the incidence of CMV disease. Viral kinetic parameters calculated were the VL duplication time (Td) and the basic reproductive number (R0). For the assessment of viral kinetics we used the maximal VL of 10 patients who had a VL determined within the previous week. Results Forty CMV D/R+ LTR were included. The median age was 52 years, 65% were women. The mean MELD score was 18, 83% of patients had decompensated cirrhosis. No patient developed CMV disease during the first 6 months after LT. Nineteen patients (47%) had CMV DNAemia, but only 8 (20%) required antiviral therapy. The highest VLs were observed during the second month after transplant. The median duplication time was 2.14 days. The median R0 was 1.46. Conclusion Although limited by our sample size, our algorithm appears useful for discriminating the patients who need antiviral treatment from those who will only have asymptomatic DNAemia. The study population VL, Td and R0 behave as described by other groups, which emphasizes the need for frequent monitoring. This is a challenge for CMV prevention in resource-limited countries. Disclosures All authors: No reported disclosures.

Plasma Hepatitis E Virus Kinetics in Solid Organ Transplant Patients Receiving Ribavirin

Hepatitis E virus (HEV) infection causes chronic hepatitis in solid organ transplant (SOT) recipients. Antiviral therapy consists of three months of ribavirin, although response rates are not optimal. We characterized plasma HEV kinetic patterns in 41 SOT patients during ribavirin therapy. After a median pharmacological delay of three (range: 0–21) days, plasma HEV declined from a median baseline level of 6.12 (3.53–7.45) log copies/mL in four viral kinetic patterns: (i) monophasic (n = 18), (ii) biphasic (n = 13), (iii) triphasic (n = 8), and (iv) flat-partial response (n = 2). The mean plasma HEV half-life was estimated to be 2.0 ± 0.96 days. Twenty-five patients (61%) had a sustained virological response (SVR) 24 weeks after completion of therapy. Viral kinetic patterns (i)–(iii) were not associated with baseline characteristics or outcome of therapy. A flat-partial response was associated with treatment failure. All patients with a log concentration decrease of plasma HEV at day seven of >15% from baseline achieved SVR. In conclusion, viral kinetic modeling of plasma HEV under ribavirin therapy showed, for the first time, four distinct kinetic profiles, a median pharmacologic delay of three days, and an estimated HEV half-life of two days. Viral kinetic patterns were not associated with response to therapy, with the exception of a flat-partial response.

Influenza Virus Infection Model With Density Dependence Supports Biphasic Viral Decay

Mathematical models that describe infection kinetics help elucidate the time scales, effectiveness, and mechanisms underlying viral growth and infection resolution. For influenza A virus (IAV) infections, the standard viral kinetic model has been used to investigate the effect of different IAV proteins, immune mechanisms, antiviral actions, and bacterial coinfection, among others. We sought to further define the kinetics of IAV infections by infecting mice with influenza A/PR8 and measuring viral loads with high frequency and precision over the course of infection. The data highlighted dynamics that were not previously noted, including viral titers that remain elevated for several days during mid-infection and a sharp 4-5 log10decline in virus within one day as the infection resolves. The standard viral kinetic model, which has been widely used within the field, could not capture these dynamics. Thus, we developed a new model that could simultaneously quantify the different phases of viral growth and decay with high accuracy. The model suggests that the slow and fast phases of virus decay are due to the infected cell clearance rate changing as the density of infected cells changes. To characterize this model, we fit the model to the viral load data, examined the parameter behavior, and connected the results and parameters to linear regression estimates. The resulting parameters and model dynamics revealed that the rate of viral clearance during resolution occurs 25 times faster than the clearance during mid-infection and that small decreases to this rate can significantly prolong the infection. This likely reflects the high efficiency of the adaptive immune response. The new model provides a well-characterized representation of IAV infection dynamics, is useful for analyzing and interpreting viral load dynamics in the absence of immunological data, and gives further insight into the regulation of viral control.