Greater decline in memory and global neurocognitive function in HIV/hepatitis C co-infected than in hepatitis C mono-infected patients treated with pegylated interferon and ribavirin.

The human immunodeficiency virus (HIV), hepatitis C virus (HCV), and the treatment of HCV with pegylated interferon and ribavirin (IFN/RBV) have been associated with neurocognitive and psychiatric abnormalities. The goal of this research was to prospectively evaluate neurocognitive functioning among a group of HCV mono-infected and HIV/HCV co-infected patients during the first 24 weeks of IFN/RBV treatment while accounting for practice effects, normal variations in change over time, and variations in IFN/RBV treatment exposure. Forty-four HCV mono-infected and 30 HIV/HCV co-infected patients were enrolled in a prospective study of patients beginning on IFN/RBV for chronic HCV infection. Patients were administered a depression inventory, a measure of fatigue, a structured psychiatric interview, and a neurocognitive battery at baseline and 24 weeks after initiation of treatment. Analyses were conducted to explore possible associations between neurocognitive functioning and the following: HIV/HCV co-infection vs. HCV mono-infection, IFN and RBV treatment exposure, psychiatric status, liver disease stage, and other medical characteristics. At baseline, there were no significant differences between the two groups' neuropsychiatric or neurocognitive function other than the mono-infected group had significantly higher reports of fatigue (p = 0.033). Over the course of 24 weeks of treatment after controlling for practice effects, the HIV/HCV co-infected patients experienced significantly greater declines in memory (t(56) = 2.14, p = 0.037) and global neurocognitive functioning (t(53) = 2.28, p = 0.027). In a well-characterized sample of mono-infected and co-infected patients, it appears that persons with HIV/HCV co-infection are potentially more vulnerable to neurocognitive sequalae during HCV treatment.

Costs of telaprevir-based triple therapy for hepatitis C: $189,000 per sustained virological response.

UNLABELLED: In registration trials, triple therapy with telaprevir (TVR), pegylated interferon (Peg-IFN), and ribavirin (RBV) achieved sustained virological response (SVR) rates between 64% and 75%, but the clinical effectiveness and economic burdens of this treatment in real-world practice remain to be determined. Records of 147 patients who initiated TVR-based triple therapy at the Mount Sinai Medical Center (May-December 2011) were reviewed. Direct medical costs for pretreatment, on-treatment, and posttreatment care were calculated using data from Medicare reimbursement databases, RED Book, and the Healthcare Cost and Utilization Project database. Costs are presented in 2012 U.S. dollars. SVR (undetectable hepatitis C virus [HCV] RNA 24 weeks after the end of treatment) was determined on an intention-to-treat basis. Cost per SVR was calculated by dividing the median cost by the SVR rate. Median age of the 147 patients was 56 years (interquartile range [IQR] = 51-61), 68% were male, 19% were black, 11% had human immunodeficiency virus/HCV coinfection, 36% had advanced fibrosis/cirrhosis (FIB-4 scores ≥3.25), and 44% achieved an SVR. The total cost of care was $11.56 million. Median cost of care was $83,721 per patient (IQR = $66,652-$98,102). The median cost per SVR was $189,338 (IQR = $150,735-$221,860). Total costs were TVR (61%), IFN (24%), RBV (4%), adverse event management (8%), professional fees (2%), and laboratory tests (1%). CONCLUSIONS: TVR and Peg-IFN accounted for 85% of costs. Pharmaceutical prices and the low (44%) SVR rate, in this real-world study, were major contributors to the high cost per SVR.

Diabetes mellitus and advanced liver fibrosis are risk factors for severe anaemia during telaprevir-based triple therapy.

BACKGROUND & AIMS: Adding telaprevir to pegylated-interferon and ribavirin increased both response rates and side effects of hepatitis C virus (HCV) treatment. We identified variables associated with severe anaemia during telaprevir-based triple therapy. METHODS: An observational study was performed on 142 HCV-infected patients between June 2011 and March 2012. All subjects completed 12 weeks of telaprevir-based triple therapy or discontinued early because of anaemia. Severe anaemia was defined by a haemoglobin≤8.9 g/dl; advanced fibrosis was determined by Fib-4≥3.25. RESULTS: The 47 (33%) patients who developed severe anaemia were similar to those who did not in sex, race, and prior response to dual therapy, but they were more likely to have diabetes (23.4% vs. 6.3%, P<0.01), advanced fibrosis (46.8% vs. 29.5%, P=0.04) and a history of anaemia during previous dual therapy (29.7% vs. 11.4%, P=0.02). Patients developing severe anaemia were older (59 vs. 56 years, P=0.02), had lower baseline platelet counts (134 vs. 163×10(9) /L, P=0.04), haemoglobin (14.0 vs. 15.0 g/dl, P<0.01), estimated glomerular filtration rate (79 vs. 90 ml/min/1.73 m2, P=0.03) and a higher median ribavirin/weight ratio (14.9 vs. 13.2 mg/kg, P<0.01). In multivariable logistic regression, presence of diabetes (OR=5.61, 95% CI: 1.59-19.72), Fib-4≥3.25 (OR=3.09, 95% CI: 1.28-7.46), higher ribavirin/weight ratio (OR=1.31 per mg/kg, 95% CI: 1.13-1.52) and lower baseline haemoglobin (OR=0.57 per g/dl, 95% CI, 0.41-0.80) were independently associated with developing severe anaemia. CONCLUSIONS: Severe anaemia occurred in one-third of patients receiving telaprevir-based triple therapy. Risk was greater in patients with diabetes, advanced liver fibrosis, higher ribavirin/weight ratio and lower baseline haemoglobin.

Combination therapy with telaprevir for chronic hepatitis C virus genotype 1 infection in patients with HIV: a randomized trial.

BACKGROUND: Telaprevir (TVR) plus peginterferon-α2a (PEG-IFN-α2a) and ribavirin substantially increases treatment efficacy for genotype 1 chronic hepatitis C virus (HCV) infection versus PEG-IFN-α2a-ribavirin alone. Its safety and efficacy in patients with HCV and HIV-1 are unknown. OBJECTIVE: To assess the safety and efficacy of TVR plus PEG-IFN-α2a-ribavirin in patients with genotype 1 HCV and HIV-1 and to evaluate pharmacokinetics of TVR and antiretrovirals during coadministration. DESIGN: Phase 2a, randomized, double-blind, placebo-controlled study. (ClinicalTrials.gov: NCT00983853). SETTING: 16 international multicenter sites. PATIENTS: 62 patients with HCV genotype 1 and HIV-1 who were HCV treatment-naive and receiving 0 or 1 of 2 antiretroviral regimens were randomly assigned to TVR plus PEG-IFN-α2a-ribavirin or placebo plus PEG-IFN-α2a-ribavirin for 12 weeks, plus 36 weeks of PEG-IFN-α2a-ribavirin. MEASUREMENTS: HCV RNA concentrations. RESULTS: Pruritus, headache, nausea, rash, and dizziness were higher with TVR plus PEG-IFN-α2a-ribavirin during the first 12 weeks. During this period, serious adverse events occurred in 5% (2 in 38) of those receiving TVR plus PEG-IFN-α2a-ribavirin and 0% (0 in 22) of those receiving placebo plus PEG-IFN-α2a-ribavirin; the same number in both groups discontinued treatment due to adverse events. Sustained virologic response occurred in 74% (28 in 38) of patients receiving TVR plus PEG-IFN-α2a-ribavirin and 45% (10 in 22) of patients receiving placebo plus PEG-IFN-α2a-ribavirin. Rapid HCV suppression was seen with TVR plus PEG-IFN-α2a-ribavirin (68% [26 in 38 patients] vs. 0% [0 in 22 patients] undetectable HCV RNA levels by week 4). Two patients had on-treatment HCV breakthrough with TVR-resistant variants. Patients treated with antiretroviral drugs had no HIV breakthroughs; antiretroviral exposure was not substantially modified by TVR. LIMITATION: Small sample size and appreciable dropout rate. CONCLUSION: In patients with HCV and HIV-1, more adverse events occurred with TVR versus placebo plus PEG-IFN-α2a-ribavirin; these were similar in nature and severity to those in patients with HCV treated with TVR. With or without concomitant antiretrovirals, sustained virologic response rates were higher in patients treated with TVR versus placebo plus PEG-IFN-α2a-ribavirin.

Insulin resistance predicts re-treatment failure in an efficacy study of peginterferon-α-2a and ribavirin in HIV/HCV co-infected patients.

BACKGROUND & AIMS: Few studies evaluated the efficacy of HCV re-treatment and the predictors of response in HIV/HCV co-infected patients. The role of insulin resistance as a predictor of response in this population is unknown. The aim of this study is to evaluate the safety and efficacy of pegylated interferon-α-2a and ribavirin in re-treatment of HIV/HCV co-infected patients, predictors of sustained virological response, including insulin resistance, and the relationship between insulin resistance and liver histology. METHODS: This prospective, multi-centered study included HIV/HCV co-infected patients with prior interferon-based treatment failure. Patients received pegylated interferon-α-2a and ribavirin for 48 weeks. Serum HCV RNA was measured 24 weeks post treatment to assess sustained virological response. Insulin resistance was defined as HOMA-IR >2. Correlations between baseline insulin resistance and steatosis, and/or cirrhosis were determined. RESULTS: Sustained virological response was achieved in 14/96 (15%) patients. 35% of patients with HOMA-IR < 2 (6/17) achieved sustained virological response vs 14% (5/36) of those with HOMA-IR between 2-4, and 7% (3/41) of those with HOMA-IR > 4 (p = 0.01). In multivariable analysis, insulin resistance and log10 HCV RNA were negatively associated with sustained virological response [AOR 0.17; 95% CI 0.05-0.64, p = 0.009, and AOR 0.36; 95% CI 0.14-0.93, p = 0.04, respectively]. Steatosis and cirrhosis correlated with insulin resistance (p = 0.02 and 0.03, respectively) but neither independently predicted sustained virological response. Discontinuations due to severe adverse events occurred in 8% of cases, and 2 patients died of unrelated causes. CONCLUSIONS: In HIV/HCV co-infected patients undergoing re-treatment, sustained virological response rate is low; those patients without insulin resistance are significantly more likely to achieve sustained virological response.

A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin.

BACKGROUND & AIMS: A sustained virologic response (SVR) to therapy for hepatitis C virus (HCV) infection is defined as the inability to detect HCV RNA 24 weeks after completion of treatment. Although small studies have reported that the SVR is durable and lasts for long periods, it has not been conclusively shown. METHODS: The durability of treatment responses was examined in patients originally enrolled in one of 9 randomized multicenter trials (n = 1343). The study included patients who received pegylated interferon (peginterferon) alfa-2a alone (n = 166) or in combination with ribavirin (n = 1077, including 79 patients with normal alanine aminotransferase levels and 100 patients who were coinfected with human immunodeficiency virus and HCV) and whose serum samples were negative for HCV RNA (<50 IU/mL) at their final assessment. Patients were assessed annually, from the date of last treatment, for a mean of 3.9 years (range, 0.8-7.1 years). RESULTS: Most patients (99.1%) who achieved an SVR had undetectable levels of HCV RNA in serum samples throughout the follow-up period. Serum samples from 0.9% of the patients contained HCV RNA a mean of 1.8 years (range, 1.1-2.9 years) after treatment ended. It is not clear if these patients were reinfected or experienced a relapse. CONCLUSIONS: In a large cohort of patients monitored for the durability of an SVR, the SVR was maintained for almost 4 years after treatment with peginterferon alfa-2a alone or in combination with ribavirin. In patients with chronic hepatitis C infection, the SVR is durable and these patients should be considered as cured.

A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update.

Chronic HBV infection is an important public health problem worldwide and in the United States. A treatment algorithm for the management of this disease, published previously by a panel of U.S. hepatologists, has been revised on the basis of new developments in the understanding of the disorder, the availability of more sensitive molecular diagnostic tests, and the licensure of new therapies. In addition, a better understanding of the advantages and disadvantages of new treatments has led to the development of strategies for reducing the rate of resistance associated with oral agents and optimizing treatment outcomes. This updated algorithm was based primarily on available evidence by using a systematic review of the literature. Where data were lacking, the panel relied on clinical experience and consensus expert opinion. The primary aim of antiviral therapy is durable suppression of serum HBV DNA to low or undetectable levels. Assays can now detect serum HBV DNA at levels as low as 10 IU/mL and should be used to establish a baseline level, monitor response to antiviral therapy, and survey for the development of drug resistance. Interferon alfa-2b, lamivudine, adefovir, entecavir, peginterferon alfa-2a, telbivudine, and tenofovir are approved as initial therapy for chronic hepatitis B and have certain advantages and disadvantages. Although all of these agents can be used in selected patients, the preferred first-line treatment choices are entecavir, peginterferon alfa-2a, and tenofovir. Issues for consideration for therapy include efficacy, safety, rate of resistance, method of administration, and cost.

Baseline factors prognostic of sustained virological response in patients with HIV-hepatitis C virus co-infection.

OBJECTIVE: To identify baseline characteristics predictive of a sustained virological response (SVR) in patients with HIV-hepatitis C virus (HCV) co-infection treated with interferon-based therapy. DESIGN/METHODS: A stepwise multiple logistic regression analysis was used to explore the prognostic factors associated with SVR [undetectable HCV-RNA (< 50 IU/ml) at the end of untreated follow-up in week 72]. RESULTS: In all patients (n = 853), in addition to the HCV therapy received, the factors most predictive of SVR were baseline HCV-RNA [< or = versus > 400 000 IU/ml; odds ratio (OR) 4.77; 95% confidence interval (CI) 3.15-7.22; P < 0.0001] and HCV genotype (OR 2.87; 95% CI 2.00-4.12; P < 0.0001). HIV treatment (with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor; P = 0.034), race (P = 0.027), and body mass index (P = 0.039) were also weak predictors of HCV treatment response. CONCLUSIONS: In the AIDS PEGASYS Ribavirin International Co-infection Trial (APRICOT), the predictors of SVR among HIV-HCV co-infected patients treated with peginterferon alfa-2a plus ribavirin were similar to those in patients with HCV mono-infection. The HCV genotype and pretreatment HCV-RNA level had the greatest influence on SVR.

Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients.

BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent and is associated with substantial morbidity and mortality among persons infected with the human immunodeficiency virus (HIV). We compared the efficacy and safety of pegylated interferon alfa-2a (peginterferon alfa-2a) plus either ribavirin or placebo with those of interferon alfa-2a plus ribavirin for the treatment of chronic HCV infection in patients who were also infected with HIV. METHODS: A total of 868 persons who were infected with both HIV and HCV and who had not previously been treated with interferon or ribavirin were randomly assigned to receive one of three regimens: peginterferon alfa-2a (180 microg per week) plus ribavirin (800 mg per day), peginterferon alfa-2a plus placebo, or interferon alfa-2a (3 million IU three times a week) plus ribavirin. Patients were treated for 48 weeks and followed for an additional 24 weeks. The primary end point was a sustained virologic response (defined as a serum HCV RNA level below 50 IU per milliliter at the end of follow-up, at week 72). RESULTS: The overall rate of sustained virologic response was significantly higher among the recipients of peginterferon alfa-2a plus ribavirin than among those assigned to interferon alfa-2a plus ribavirin (40 percent vs. 12 percent, P<0.001), or peginterferon alfa-2a plus placebo (40 percent vs. 20 percent, P<0.001). Among patients infected with HCV genotype 1, the rates of sustained virologic response were 29 percent with peginterferon alfa-2a plus ribavirin, 14 percent with peginterferon alfa-2a plus placebo, and 7 percent with interferon alfa-2a plus ribavirin. The corresponding rates among patients infected with HCV genotype 2 or 3 were 62 percent, 36 percent, and 20 percent. Neutropenia and thrombocytopenia were more common among patients treated with regimens that contained peginterferon alfa-2a, and anemia was more common among patients treated with regimens containing ribavirin. CONCLUSIONS: Among patients infected with both HIV and HCV, the combination of peginterferon alfa-2a plus ribavirin was significantly more effective than either interferon alfa-2a plus ribavirin or peginterferon alfa-2a monotherapy.

Treatment of acute hepatitis C in an HIV-positive man with pegylated interferon and ribavirin for 24 weeks.

An epidemic of acute hepatitis C is emerging among HIV-infected men who have sex with men (MSM), with a growing number of cases reported in the MSM population in the United States and Europe. We report a case of a 47-year-old HIV-infected MSM who sexually contracted acute hepatitis C and was treated with pegylated interferon and ribavirin for 24 weeks. After 4 weeks of therapy, the patient's HCV RNA level became undetectable and remained undetectable 1 year after the 24-week treatment course.

Cost-effectiveness of peginterferon alfa-2a (40kDa) plus ribavirin in patients with HIV and hepatitis C virus co-infection.

BACKGROUND: A multinational trial (APRICOT) showed that peginterferon alfa-2a (40kDa) plus ribavirin is efficacious for treatment of HIV-HCV co-infection. The cost-effectiveness of treating these patients with peginterferon alfa-2a/ribavirin has yet to be explored from a US societal perspective. OBJECTIVE: To predict the cost-effectiveness of peginterferon alfa-2a/ribavirin with interferon/ribavirin (IFN/RBV) or no treatment in HIV-HCV co-infected patients. STUDY DESIGN: A Markov model was constructed with liver progression estimates based on published literature. Sustained virological response and baseline characteristics of the reference case were based on APRICOT. Quality of life and costs in 2004 US dollars (US$) were based on literature estimates and discounted at 3%. RESULTS: Peginterferon alfa-2a/ribavirin compared with IFN/RBV or no treatment is predicted to increase quality-adjusted life-years (QALYs) by 0.73 and 0.94 years, respectively, in HCV-genotype-1 patients. The incremental cost-effectiveness ratio of peginterferon alfa-2a/ribavirin compared with IFN/RBV and no treatment for all patients is respectively US$ 2,082 and 5,187/QALY gained. CONCLUSIONS: Anti-HCV treatment is predicted to decrease the risk of cirrhosis and increase quality-adjusted survival of HIV-HCV co-infected patients compared with IFN/RBV and no treatment. Peginterferon alfa-2a/ribavirin's cost per QALY gained relative to these options falls within the cost-effectiveness level of many health technologies commonly adopted in the US.

Sustained virologic response with short-course ribavirin and peginterferon treatment in 2 patients coinfected with HIV and HCV genotype 1.

The current recommendation for the duration of treatment of patients infected with chronic hepatitis C virus (HCV) genotype 1 is 48 weeks; however, the standard regimen of peginterferon plus ribavirin bears significant adverse effects, which make completion of treatment exceedingly difficult. Reported here are 2 cases of HIV-HCV-coinfected genotype-1 patients who discontinued treatment early (after 3 and 8 weeks) because of adverse effects yet had a sustained virologic response with undetectable HCV viral loads at follow-up.

Treatment of hepatitis C virus in HIV patients: a review.

BACKGROUND: Survival in HIV infection has improved dramatically in the last decade due to antiretroviral therapy (ART). Due to shared routes of transmission, HCV is found in approximately 30% of HIV infected patients. HCV infection has emerged as a major issue in this population as manifest by a major increase in liver-related mortality. ART-associated hepatotoxicity has been demonstrated to occur more frequently in co-infected individuals and may be severe or fatal in some instances. Thus treatment of HCV has become a priority in HIV infected individuals. OBJECTIVES: The main aims of this review are to summarise and illustrate the current evidence based management of anti-HCV therapy in HIV-infected patients. METHODS: A systematic review of the literature was performed using Pubmed and Medline searches. CONCLUSION: All HIV-infected patients should be screened for HCV infection via anti-HCV antibody and HCV RNA polymerase chain reaction. If HCV infection is present, treatment should be considered in those patients with evidence of liver inflammation and fibrosis. Recent studies have demonstrated the safety and efficacy of anti-HCV therapy in HIV-infected individuals with pegylated interferon and ribavirin combination therapy. HCV genotype is predictive of response to therapy and increasing the duration of therapy to 48 weeks has proven to be more effective in patients with genotypes 2 and 3. HCV treatment with interferon based therapy is associated with many unique side effects and toxicities in this population of which the clinician must be aware.

Interferon-induced depression and cognitive impairment in hepatitis C virus patients: a 72 week prospective study.

OBJECTIVES: This study assessed the rates and course of depressive symptomatology and neurocognitive deficits in hepatitis C virus (HCV) patients undergoing interferon treatment, and explored possible predictors of depression and neurocognitive deficits. DESIGN: In order to obtain objective assessments of depression, and to evaluate cognitive impairment, a 72-week prospective study, comprising 48 weeks of treatment and 24 weeks of post-treatment follow-up was utilized. METHODS: A total of 50 HCV patients were assessed at baseline, and 14 times during pegylated interferon plus ribavirin treatment. Patients were also assessed on four timepoints after the termination of treatment. All patients have previously been treated for hepatitis C infection with interferon and were judged to be treatment resistant in these treatments. Depression was assessed using the Center for Epidemiological Studies Depression (CES-D) questionnaire, and patients were interviewed regarding problems with memory, attention and concentration. RESULTS: Eighty-two per cent of interferon-treated patients developed severe enough depressive symptoms to meet the CES-D criteria for possible major depressive disorder (MDD). Possible MDD onset was most frequent by the first week of treatment, and almost all possible MDD cases were observed by week 8. More severe depressive symptoms at baseline were associated with higher depressive symptoms during interferon treatment. Thirty per cent of patients complained about cognitive problems. In half of these patients cognitive impairments were still reported after the termination of treatment. There was no association between depression during interferon treatment and subjective cognitive complaints. CONCLUSIONS: The findings suggest that depression and cognitive impairments are frequent and persistent side-effects of interferon treatment in treatment-resistant patients.

Current status of the use of growth factors and other adjuvant medications in patients receiving peginterferon and ribavirin.

Hepatitis C virus (HCV) is the most common chronic infection in the United States, affecting almost 3.9 million Americans. The most effective treatment for chronic HCV infection is combination antiviral therapy with peginterferon and ribavirin. However, combination therapy is also associated with significant adverse effects and is contraindicated in certain patient populations. Hematological adverse effects are common and are a frequent cause of dose reduction and interruption or discontinuation of therapy. Currently there are no approved treatments for the hematological adverse events associated with HCV therapy. However, emerging data suggest that utilization of hematopoietic growth factors can provide a useful adjunct to treatment and optimize sustained virologic response rates.

Acute HIV seroconversion in a patient receiving pegylated interferon for treatment of hepatitis C.

Hepatitis C is diagnosed frequently in persons with HIV infection. However, the diagnosis of HIV infection during treatment of hepatitis C has not been reported. We present a case of acute HIV seroconversion in a patient who was not responding to interferon therapy for treatment of hepatitis C.

HIV/HCV coinfection in clinical practice.

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) frequently co-exist due to shared routes of transmission. In the past, the impact of HCV on overall morbidity and mortality of coinfected patients was minimal due to the poor prognosis of HIV. However, since the introduction of highly active antiretroviral therapy (HAART), HCV has become a significant pathogen in this population. HIV clearly exacerbates HCV infection and accelerates progression to cirrhosis, end-stage liver disease, and hepatocellular carcinoma. There is debate over whether HCV influences the natural history of HIV. Given the high prevalence of coinfection and the accelerated liver damage, HCV treatment has become a priority in these patients. There are new data on pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy for HCV in coinfected patients. The therapy is well tolerated and safe, although it appears to be slightly less effective than in monoinfected patients. The risk of HAART-related hepatotoxicity is greater in coinfected patients and therefore requires special consideration and close monitoring.

Pegylated-IFNα2a for HIV/hepatitis C virus coinfected patients: out with the old, in with the new.

INTRODUCTION: Liver disease is a major burden in patients co-infected with HIV and hepatitis C virus (HCV). From the time of its approval, pegylated-IFNα-2a (pegIFN-α2a) has played a major role in treatment of HCV in HIV/HCV co-infection. AREAS COVERED: This article briefly summarizes the epidemiology of HCV/HIV co-infection, the pharmacokinetic, and pharmacodynamic properties of pegIFN-α2a. Results from clinical trials investigating therapies containing pegIFN-α2a for HIV/HCV co-infected patients will be discussed with a focus on efficacy and safety. EXPERT OPINION: PegIFN-α2a has improved rates of sustained virologic response for co-infected patients. In combination with direct-acting antivirals (DAA), the disparity between mono- and co-infected patients is beginning to disappear. For the first time, IFN-free regimens are available in clinical practice. It is unlikely that pegIFN-α2a will continue to be a critical component in treatments for HCV in the general co-infected population.

The pharmacokinetic evaluation of boceprevir for treatment of hepatitis C virus.

INTRODUCTION: Boceprevir is an NS3/NS4A serine protease inhibitor that was approved for use in Hepatitis C virus (HCV) genotype 1 patients by the US Food and Drug Administration (FDA) in May 2011. The approval of this protease inhibitor marked a major paradigm shift in the treatment of HCV, as it was one of the first of many new small molecules specifically designed and approved for HCV. AREAS COVERED: In this article, the authors summarize boceprevir's pharmacokinetic and pharmacodynamic properties. In addition, they review Phase II and III trials of boceprevir as well as its clinical efficacy, dosing and safety. EXPERT OPINION: Boceprevir is a potent protease inhibitor for the treatment of genotype 1 HCV. It has a well-tolerated side-effect profile and increases the likelihood of SVR in naïve and previously treated patients. The impending release of newer more efficacious direct-acting antivirals may limit the use of boceprevir for patients infected with HCV.

Update on combinations of DAAs with and without pegylated-interferon and ribavirin: triple and quadruple therapy more than doubles SVR.

Monotherapy is an ineffective way to treat hepatitis C and it leads to rapid development of resistance. An increasing number of drugs are currently being developed for the treatment of hepatitis C. This allows combination strategies that can overcome the development of resistance and improve sustained virologic response rates. This article focuses on the 2 main strategies in development: quadruple combination therapies, including pegylated-interferon and triple/quadruple pegylated-interferon free combination therapies. If the first combinations are leading to extremely high sustained virologic responses, the second ones offer hope that the era of pegylated-interferon will end soon.