ABSTRACT
BACKGROUND & AIMS: The first generation protease inhibitors, boceprevir (BOC) and telaprevir (TVR), are both CYP3A4 inhibitors, which predispose drug-drug interactions (DDIs). The aim of this study was to evaluate the prevalence of potential DDIs, the management of outpatient medication and its impact on adherence and efficacy to antiviral treatment in hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients receiving BOC and TVR. METHODS: The usual medication starting with BOC or TVR was screened by the pharmacist of the multidisciplinary support programme (MSP) for potential DDIs. Recommendations were made to avoid significant DDIs, and changes in the baseline medication were recorded. Adherence to antiviral treatment was considered as 80/80/95% of total doses. Sustained virological response was assessed at week 12 (SVR12). RESULTS: At least one potential DDI was found in 70 (64.8%) patients, 45 (54.2%) being HCV-monoinfected and 25 (100%) HIV/HCV-coinfected (P < 0.01). Baseline treatment modifications were required in 38 (35.2%) patients. Adherence and SVR12 were higher in patients without DDIs (86.8%) and (67.6%) compared to those with DDIs (62.8%) (P = 0.021) and (47.2%) (P = 0.097) respectively. CONCLUSIONS: More than half of the patients were at risk of presenting DDIs, leading to changes in the baseline medication in one-third of the patients. Drug interactions are frequent in patients with lower adherence.
Subject(s)
Antiviral Agents/therapeutic use , Coinfection/drug therapy , HIV Infections/drug therapy , Hepatitis C, Chronic/drug therapy , Oligopeptides/therapeutic use , Proline/analogs & derivatives , Protease Inhibitors/therapeutic use , Adult , Aged , Drug Interactions , Drug Therapy, Combination , Female , Follow-Up Studies , Genotype , Hepacivirus , Humans , Interferon-alpha/therapeutic use , Logistic Models , Male , Middle Aged , Multivariate Analysis , Polyethylene Glycols/therapeutic use , Proline/therapeutic use , Recombinant Proteins/therapeutic use , Ribavirin/therapeutic useABSTRACT
BACKGROUND & AIMS: Since the International Ascites Club published the diagnostic criteria of refractory ascites (RA) and hepatorenal syndrome (HRS), there have been few studies assessing the natural history of ascites. The aims of this study were to define the natural history of cirrhotic ascites and to identify prognostic factors for dilutional hyponatremia (DH), RA, HRS, and survival. METHODS: Two hundred sixty-three consecutive cirrhotic patients were followed for 40.9 +/- 2.6 months after their first significant ascites. RESULTS: During follow-up 74 (28.1%) patients developed DH, 30 (11.4%) RA (diuretic-resistant in 2 cases and diuretic-intractable because of the development of diuretic-induced complications in 28 cases), and 20 (7.6%) HRS (type 1, 7; type 2, 13). The 5-year probability of DH, RA, and HRS development was 37.1%, 11.4%, and 11.4%, respectively. The probability of survival at 1 and 5 years was 85% and 56.5%, respectively. The independent predictors for survival were baseline age, baseline Child-Pugh score, and DH development. The 1-year probability of survival after developing DH, RA, and type 2 HRS was 25.6%, 31.6%, and 38.5%, respectively. In contrast, the mean survival was only 7 +/- 2 days in those patients developing type 1 HRS. CONCLUSIONS: (1) The survival of cirrhotic patients with first episode of ascites is relatively high, and it is mainly influenced by age and Child-Pugh score at the time of ascites decompensation, as well as by DH development. (2) The probability of RA and HRS development is relatively low, but they are associated with a poor prognosis.
