Background/Aims: Chronic hepatitis C (HCV) virus infection reactivates under immunosuppressive drugs and therefore has a negative impact on long-term survival of kidney transplant recipients. Treatment-induced clearance of hepatitis C virus (HCV) in kidney transplant candidates prevents virus reactivation after transplantation. Paritaprevir/Ritonavir/Ombitasvir with Dasabuvir (PrOD) represents a highly effective treatment regimen for HCV genotype 1 (GT1), also suitable for patients with end-stage renal disease (ESRD). Serious drug-drug interactions may represent a limiting factor of this regimen. The aim of this retrospective study was to evaluate safety, efficacy and drug-drug interactions management associated with PrOD treatment in the Czech real-world cohort. Methods: Emphasizing concomitant medication adjustment, we described the treatment course with PrOD regimen in 23 patients (4 with CKD4 and 19 on maintenance haemodialysis) infected with HCV GT1 (21 GT1b, 2 GT1a), 18 males and 5 females with an average age of 53.7 years. Six patients had compensated liver cirrhosis and 3 of them were liver transplant recipients. Results: All 23 patients completed the 12-week treatment and achieved sustained virological response 12 weeks after the treatment (SVR12 rate 100%). None of the patients presented with a significant decrease in haemoglobin level, white blood cell and platelet count during the treatment period. The most frequent adverse events were nausea, hypotension, diarrhoea, and hyperkalemia. Four patients presented with a serious adverse event unrelated to the antiviral drugs (salmonellosis, non-functional kidney graft rejection, early gastric cancer, renal cyst infection, initiation of haemodialysis). Concomitant medication had to be modified with the treatment initiation in 10 out of 23 (43.5%) patients (calcium channel blockers, ACE inhibitors, statins, diuretics, tacrolimus); four patients required further adjustment of antihypertensive drugs or tacrolimus dosage on-treatment. Conclusion: PrOD regimen demonstrated an excellent efficacy and good tolerability. Both prospective adjustment of concomitant medication and further on-treatment adjustment allowed for a safe treatment course.

The formation of poly(rU) complexes with diadenosine monophosphate (3 -5 ) and its four isopolar, nonisosteric phosphonate analogues was studied by means of Raman spectroscopic titration. A set of mixed samples containing the diadenosine monophosphate or monophosphonate and the poly(rU) at various concentration ratios was prepared. The room temperature spectra of mixed solutions were treated by factor analysis and decomposition of the Raman marker bands. For all the species studied, the results revealed an exclusive presence of the triplex-like complexes, i.e. complexes with a 1 : 2 stoichiometric ratio of the adenosine to uridine units, the Raman spectra of which exhibit all the features typical of the poly(rU)·poly(rA)·poly(rU) triple-helical structure. The individual molar fractions of the free ApA dimer, the free poly(rU) and the triplex-like complex do not fit classical equilibrium equation, because the binding ability of the adenosine dimers to poly(rU) falls significantly for small ApA molar fractions. This tendency is strongest for the natural diadenosine phosphate (3 -5 ) and weakest for two analogues in which the -CH 2 -group in the modified internucleotide linkage is situated closer to the 5 -position.