December 12, 2013

Online Hepatitis C Support Groups

There are some really good support groups on the internet. These are just a few links I have in my collection. If you have others that you would like to see added, please feel free to contact me.

 

Hepatitis C Family and Friends (Facebook Group)

Liver Failure Support Group (Delphi Forums) – Quick free registration

Hep Forums (Hep Magazine)

Daily Strength Hepatitis C Support Group – Quick free registration

HCV Support Forums (HCV Support,org) -- Quick free registration

Hep C Nomads (Based in the UK) --  Quick free registration

The UK Hepatitis C Forum -- Quick free registration

Hep C Friends --  Quick free registration

Hep C Vets (Facebook Group)

 

Updated December 12, 2013 9:42 pm EST

The Story Behind ‘Hepatitis C Research and News’

Small_HCV

My name is Patricia, I have been online giving support and raising awareness since 2002. I was diagnosed with HCV in 2002. Genotype 3a. Biopsy showed Stage 3 Grade 3, viral load 800,000IU. I treated the first time in 2002 with Pegintron + Ribavirin yet was pulled off Ribavirin within the first ten days due to very low counts (having to be transfused), I continued with Peg monotherapy for 9 months yet I did not respond. I was told that I could never take Ribavirin again that my body could not tolerate it. I was not ready to give up. I found a wonderful Hepatologist at Duke University, Dr. Andrew Muir. He told me that we would try again, but this time they would give me Procrit if my counts started to bottom, which they did after the first 9 weeks. I retreated with Pegasys + Ribavirin starting on January 13, 2005 my starting viral load was 3,124,000IU and by week 8 was undetected. I finished 43 of 48 weeks of treatment on November 3, 2005 stopping 5 weeks early after having had 2 blood transfusions and even with Procrit my counts still bottoming out. I achieved SVR as of May 2006.

I have been involved with HCV support since I was diagnosed, learning everything that I could about this insidious disease and trying to give back the support that was so freely given to me. I remember that day that I was diagnosed, how scared I was and so naive when it came to Hepatitis C, My hope over the years has been to keep others from feeling the way that I did.

I started this blog in June 2010, expanded to Twitter and Facebook later that year. Reaching out to learn as well as educate. In January 2012 I started a support group on Facebook “Hepatitis C Family and Friends” it is a safe haven where people can go and find the love and support from others that are going through the same things. It is definitely a group of ‘family’ and ‘friends’.

I am not a writer, yet my goal of this blog is to provide a place where people come and find the most up to date research and information on Hepatitis C, as well as HIV/HCV co-infection and other liver diseases. This year has been one of the most exciting in hepatitis C research since I have been involved with HCV awareness, so much promise in the pipeline coming with new drugs over the next few years.

As much as I enjoy what I do here on the internet and social media, I do hope and pray that someday soon, this blog will no longer be needed, for a cure has been found. Until then I will continue to provide you with the latest research and news.

Patricia Emory
Hepatitis C Research and News

Updated December 12, 2013 9:08 pm EST

Hepatitis C Virus Serosorting in People Who Inject Drugs

Provided by NATAP

Download the PDF here

Download the PDF here

The Journal of Infectious Diseases Dec 15 2013

" These complexities have the potential to result in incorrect perceptions or interpretations of HCV infectiousness. Thus, serosorting is even less likely to be effective as a preventive strategy among PWID to avoid HCV than the parallel sexual behaviors observed among MSM to avoid HIV-1......In an ideal world, all results would be at the point of care and rapidly obtained to enhance the provider's ability to counsel and refer patients. "

"Future studies should examine in more detail the consequences and potential utility of HCV testing and counseling, including the understanding that PWID and others have of their HCV testing results, and how they interpret and use these in decision making and risk assessments. Prospective studies in PWID are needed to assess the durability of counseling messages on individual behaviors and within injecting partnerships, which are often complex and vary significantly over time and arrangement (eg, cohabitating, sexual) [13]. Increasing "PWID's awareness of their HCV status will have important consequences for public health" [8] only if testing is both accurate and comprehensive, then accompanied by counseling that is truly informative of those at risk of and with infection, and finally followed by linkage to treatment."

"This article is not intended to promote injection equipment serosorting as a HCV risk-reduction strategy for PWID but to report that participants were more likely to share syringes with persons of concordant serostatus. One problem that can be expected if injection equipment serosorting is adopted by PWID is the potential effect of incomplete knowledge of infection status. If PWID know they are anti-HCV positive but mistakenly believe they are infected (when they have actually cleared the virus and are negative for HCV RNA), they could opt to serosort injection equipment with infected persons based on this misunderstanding, placing themselves at risk. This issue highlights the importance of conducting HCV RNA tests for all HCV antibody-positive persons and ensuring that they receive and understand their results.

A similar challenge that arises when PWID serosort by injection equipment is the injecting partner's knowledge of their own HCV status. This requires both accurate knowledge and understanding by the injection partner and full disclosure of their HCV status. Although there are proven effective HIV testing and counseling interventions [30], as well as effective interventions to improve disclosure skills for HIV-positive persons [31], there are no HCV-specific interventions to improve either of these factors. Much can be learned from these established interventions, but HCV test results and counseling messages and disclosure issues require more nuanced communication given the 2-step testing process to determine HCV-infection status and the knowledge needed to understand and disclose that information to injection partners."

-----------------------

Hepatitis C Virus Serosorting in People Who Inject Drugs: Sorting Out the Details - Editorial Commentary

original article follows below after editorial

The Journal of Infectious Diseases Dec 15 2013

Arthur Y. Kim1,a and Kimberly Page2,a
1Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston; and 2Department of Epidemiology and Biostatistics, University of California, San Francisco

In developed countries such as the United States, hepatitis C virus (HCV) is primarily transmitted between people who inject drugs (PWID) due to the combination of high existing prevalence in the population, HCV's high infectivity, and repeated exposures to multiple potential contaminated sources of both drug preparation and administration equipment [1-3]. Although HCV incidence has declined since the 1990s in the United States, and several studies suggest it has been stable in the past decade [4], newly detected outbreaks of HCV in multiple areas of the United States, especially in suburban and rural (or "exurban") settings, have been tied to increasing rates of opiate use in young adults [5, 6]. These new outbreaks raise serious concerns as HCV quickly reaches epidemic levels, as seen among adolescents and young adults in Massachusetts [7].

Further dissection of risk factors and behaviors that govern HCV risk related to injection practices in PWID is welcomed. In this issue of The Journal of Infectious Diseases, Smith et al present intriguing data that suggest that PWID throughout the United States are engaging in "serosorting," defined as a decision to share or not to share injection equipment based on the partner's HCV serostatus [8]. A person injecting drugs who is HCV seropositive will worry less about acquisition if the sharing partner is also HCV positive; conversely, someone who perceives himself or herself to be HCV negative will seek HCV-negative partners to avoid acquisition.

For human immunodeficiency virus type 1 (HIV-1), serosorting has been previously described in men who have sex with men, as a seroadaptive strategy aimed at preventing HIV transmission-for instance, choosing sex partners with concordant HIV status [9, 10]. For HCV, less is known about serosorting. One study among young injection drug users found that knowledge about one's own serostatus correlated with higher knowledge about transmission of HCV but not with reduced distributive or receptive syringe sharing [11]; this study did not evaluate participants' knowledge or perception of their partner's serostatus. Results from subsequent single-center studies that assessed seroadaptive behavior in PWID and examined perceived partner serostatus for HCV [12, 13] and HIV [14] do support that it influences whether to share or not share injecting equipment. In fact, in one of those studies [12], 39% of participants who reported sharing equipment said serosorting was an intentional strategy. The present study provides further evidence of seroadaptive behavior among PWID in association with HCV, and indicates that this behavior may be common on a national level. By asking about the testing history of last injection partner as a preface to participants' awareness of their partners' HCV status, the authors increase the potential for higher internal validity of this self-reported measure in their analyses. They found strong independent associations indicative of serosorting between both self-reported HCV-positive and -negative respondents: the former with higher, and the latter with lower, odds of sharing with HCV-positive partners compared to those with unknown HCV status. An additional strength of this study was the very large and well-sampled population of PWID from multiple urban centers.

As the authors point out, inference about intention is limited; this study, like others, was cross-sectional, and it cannot be determined if the participants made selective decisions about behavior or if the behavioral mixing influenced knowledge of and testing for HCV. To gain further knowledge, both prospective studies as well as measures regarding seroadaptive intention are needed. One important limitation of the current study was reliance of self-reported HCV infection status, as actual test results of the respondents and their partners were not present.

This study shows that HCV testing and counseling may influence injecting behavior of PWID. It is remarkable that up to 75% of PWID at these centers reported a perceived serostatus for themselves. Although almost half of the participants reported sharing injecting equipment, more than a third (37.7%) of those reported knowledge of their injecting partners' serostatus, based on testing history [8]. These numbers imply that testing has been widely applied in this population and that status is shared among injecting groups. What is not clear is whether testing is as widespread in nonurban settings, such as the "exurban" areas where opiate use and HCV cases may be rising.

Moreover, it remains unclear whether appropriate counseling about the meaning of a positive result and, specifically, regarding infectiousness has been communicated. PWID are infectious if they have HCV RNA in the blood compartment. Testing algorithms have suggested that all HCV antibody-positive persons receive confirmation of viremia via a nucleic acid test [15], not only because approximately 20% of those infected clear virus (and are not infectious), but also because of false-positive anti-HCV tests. Although there are alternative approaches, such as reflexive testing on a single sample (mostly for anti-HCV confirmation), in practice, 2-stage testing for HCV RNA following a positive screening enzyme-linked immunosorbent assay (ELISA) is the most widely utilized approach. For a variety of reasons, including competing priorities and the cost and time associated with multiple visits for counseling, it is not clear that nucleic acid tests have been widely applied or that knowledge regarding the nuances of HCV results have been disseminated among PWID.

For someone choosing to avoid acquisition of HIV-1, serosorting to guide choice of sexual partners makes intuitive sense, as a positive result, when combined with an idea of treatment status (being off antiretrovirals), correlates with infectiousness. In contrast, HCV serostatus alone may not correlate with infectiousness, as a positive HCV antibody result simply indicates exposure without information regarding viremia in the bloodstream. This results in potential misclassification of infectious status between partners for at least 2 major reasons: (1) During acute HCV infection, there is a relatively long period averaging 6 weeks where HCV antibody is negative but viremia is present, when exposed individuals may perceive themselves to be negative; and (2) a significant proportion of untreated individuals infected with HCV, especially more women, will spontaneously clear the virus and, thus, be noninfectious [16]. Moreover, clearing virus does not eliminate susceptibility; seropositive individuals who have spontaneously cleared the virus remain at risk for reinfection. Counseling messages that accompany routine HCV testing are, therefore, more complex than for other infections such as HIV, and are parallel to those for human papillomavirus, another infection with a possibility of clearance. These complexities have the potential to result in incorrect perceptions or interpretations of HCV infectiousness. Thus, serosorting is even less likely to be effective as a preventive strategy among PWID to avoid HCV than the parallel sexual behaviors observed among MSM to avoid HIV-1.

Recent recommendations by the Centers for Disease Control and Prevention [17], endorsed by the US Preventive Services Task Force, call for more widespread HCV testing [18]. Among PWID, regular testing that is comprehensive and includes HCV RNA to confirm a positive screening ELISA test will have the benefit of providing information about infectiousness, in addition to follow-up for clinical care to avoid long-term risks for premature death due to liver disease. The results may not only inform future behaviors, including seroadaptive ones, but also care seeking. In an ideal world, all results would be at the point of care and rapidly obtained to enhance the provider's ability to counsel and refer patients. The test would be less costly than current viral titer measurements to allow for greater implementation, especially when resources are limited. At present, the most recent-generation tests for HIV-1 combine antibody and antigen testing to capture the acute stage; parallel development of similar tests for HCV would obviate the 2-step testing algorithm currently recommended, but are currently not available.

Future studies should examine in more detail the consequences and potential utility of HCV testing and counseling, including the understanding that PWID and others have of their HCV testing results, and how they interpret and use these in decision making and risk assessments. Prospective studies in PWID are needed to assess the durability of counseling messages on individual behaviors and within injecting partnerships, which are often complex and vary significantly over time and arrangement (eg, cohabitating, sexual) [13]. Increasing "PWID's awareness of their HCV status will have important consequences for public health" [8] only if testing is both accurate and comprehensive, then accompanied by counseling that is truly informative of those at risk of and with infection, and finally followed by linkage to treatment.

--------------------------------

"To Share or Not to Share?" Serosorting by Hepatitis C Status in the Sharing of Drug Injection Equipment Among NHBS-IDU2 Participants\

The Journal of Infectious Diseases Dec 15 2013

Bryce D. Smith,1 Amy Jewett,2 Richard D. Burt,3 Jon E. Zibbell,1 Anthony K. Yartel,4 and Elizabeth DiNenno5 1Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia; 2Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee; 3Public Health Seattle and King County, Seattle, Washington; 4Centers for Disease Control and Prevention Foundation, Atlanta, Georgia; and 5Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia

Abstract

Background. Persons who inject drugs (PWID) are at high risk for acquiring hepatitis C virus (HCV) infection. The Centers for Disease Control and Prevention estimates there are 17 000 new infections per year, mainly among PWID. This study examines injection equipment serosorting-considering HCV serostatus when deciding whether and with whom to share injection equipment. Objective. To examine whether injection equipment serosorting is occurring among PWID in selected cities.

Methods. Using data from the National HIV Behavioral Surveillance System-Injection Drug Users (NHBS-IDU2, 2009), we developed multivariate logistic regression models to examine the extent to which participants' self-reported HCV status is associated with their injection equipment serosorting behavior and knowledge of last injecting partner's HCV status. Results. Participants who knew their HCV status were more likely to know the HCV status of their last injecting partner, compared to those who did not know their status (HCV+: adjusted odds ratio [aOR] 4.1, 95% confidence interval [CI], 3.4-4.9; HCV-: aOR 2.5, 95% CI, 2.0-3.0). Participants who reported being HCV+, relative to those of unknown HCV status, were 5 times more likely to share injection equipment with a partner of HCV-positive status (aOR 4.8, 95% CI, 3.9-6.0).

Conclusions. Our analysis suggests PWID are more likely to share injection equipment with persons of concordant HCV status.

The Centers for Disease Control and Prevention (CDC) estimates that 4.1 million Americans have been infected with the hepatitis C virus (HCV) with 75%-80% of those chronically infected [1]. While CDC recommendsroutine antibody testing for persons at risk of HCV exposure [2], recent studies estimate 40%-85% of HCV-infected persons are unaware of their infection status [3-5]. This lack of awareness has important consequences for disease prevention because knowledge of HCV status is often a prerequisite to making health-promoting behavioral changes and treatment decisions.

HCV prevalence has reached epidemic proportions in the United States and is endemic among persons who inject drugs (PWID). HCV is primarily by percutaneous exposure to contaminated blood, making injection drug use (IDU) the leading cause of incidence in the United States. HCV prevalence among PWID resides between 30% and 70%, depending on frequency and duration of use, and incidence ranges from 16%-42% per year [6-8].

With such high prevalence of infection, recent attention has focused on factors that influence a person's decision to share or not to share injection equipment (IE). One such factor is serostatus, particularly the question as to whether knowing one's HCV status, and that of a prospective partner, affects a person's decision to share IE. We suggest the complex relationship between a person's serostatus and their decision to share IE can be illuminated, in part, through the concept of serosorting.

Serosorting occurs when viral serostatus serves as a determining factor in a person's choice of sex or drug-injecting partners and in the selection of behaviors stemming from that choice. The term has traditionally been used to describe men who have sex with men (MSM), who deliberately select sex partners based on their own and their prospective partner's human immunodeficiency virus (HIV) serostatus [9]. Here, serostatus is characterized as a type of measure whereby people choose a sexual partner based on their own and their partner's HIV status and then base the extent of their sexual activity on that knowledge for the specific purpose of reducing the risk of acquiring or transmitting HIV. While serosorting has been used most notably to describe the sexual choices of MSM, researchers have recently found similar trends among PWID [10-12]: one study in Seattle reported PWID were more likely to share injection equipment with the last injecting partner of concordant status [10]; an investigation in San Francisco found those who perceived their injecting partner to be HCV-positive were less likely to engage in receptive needle sharing [11]; and in Baltimore, HIV-positive participants reported being less likely to serosort than HIV-negative participants [12]. Bearing in mind these city-specific trends, this study expands their scope by examining injection equipment serosorting among PWID on a national scale. Specifically, we examine the relationships between participant's self-reported HCV status and (a) injection equipment sharing behavior, (b) knowledge of last injecting partner's HCV status (known/unknown), and (c) last injecting partner's HCV status (positive/negative).

METHODS

National HIV Behavioral Surveillance System (NHBS)

NHBS is a community-based survey that conducts interviews in triennial cycles among MSM, heterosexuals at increased risk for HIV infection, and PWID. Its purpose is to track the prevalence of and trends in HIV-related risk behaviors, including sex and injection drug use, and to record levels of HIV testing and the use of HIV prevention services among persons at high risk for HIV transmission such as PWID [13]. The second IDU cycle (NHBS-IDU2) was conducted between September and December 2009 and employed respondent-driven sampling (RDS) [14] to target individuals from social networks that can serve as seeds to recruit their peers into the study. Participating sites included in this analysis were located in Atlanta, Baltimore, Boston, Chicago, Dallas, Denver, Detroit, Houston, Los Angeles, Miami, Nassau, Newark, New Orleans, New York, Philadelphia, San Diego, San Francisco, San Juan, Seattle, and Washington, DC. Across the 20 sites, 10 352 respondents were eligible for NHBS-IDU2 and participated in the study. The current study was restricted to 9690 participants with valid responses to questions concerning their HCV status and the HCV status of their last injection equipment sharing partner within the previous 12 months.

Outcome Measures

The outcomes of interest were (a) injection equipment sharing behavior, (b) knowledge of last injecting partner's HCV status (known/unknown), and (c) last injecting partner's HCV status (positive/negative). The HCV status of respondent and respondent's last injecting partner were both self-reported by the respondent. The HCV status of respondent's last injection partner was derived from the following questions: "The last time you injected with this person (last sharing partner in past 12 months), did you know if they had been tested for hepatitis C?" and if yes, "What was the result of their hepatitis C test?" Respondents were also asked a series of questions with respect to their injection equipment sharing behaviors over the previous 12 months. Equipment sharing was defined to include the reuse of syringes, filters, cookers, water, and the practice of dividing drugs with a syringe (eg, backloading or frontloading). We categorized equipment sharing behavior in 2 different ways. For exploratory bivariate analysis, we dichotomized this variable as shared vs did not share. We also categorized the same outcome as a 4-level multinomial response variable for subsequent advanced analysis: shared with HCV-negative partner, shared with HCV-positive partner, shared with partner of unknown HCV status, or shared no injection equipment.

Independent Variables

\The primary independent variable was respondent's HCV status. Based on a review of the literature regarding HCV and injection equipment sharing, we also included the following variables as confounders and/or independent predictors: respondent's gender, race/ethnicity, birth year (as proxy for age), education, homelessness, employment status, annual income, age at first injection, and duration of injection.

Data Analysis

We calculated unweighted proportions to describe the characteristics of the study population. Pearson χ2 tests were used to explore bivariate associations between all independent variables and outcome variables. Consistent with the stated objectives of this study, we developed 3 separate multivariate logistic regression models to evaluate the associations between the respondent's HCV status and the 3 outcome measures, adjusting for all plausible confounders.

First, we modeled equipment sharing (4-level response category) as the dependent variable in a multinomial logistic regression; participants who shared equipment with their last injecting partner of negative, positive, or unknown HCV status were compared to those who did not share. This model was based on the full analytic population (n = 9690). In the second model, we restricted our analysis to respondents who reported sharing equipment (n = 4542) and modeled respondent's knowledge of last injecting partner's HCV status (known/unknown) as the dependent variable. In the third model, we further restricted the analysis to respondents who reported awareness of their last injecting partner's HCV status (n = 1712), and modeled last injection partner's HCV status (positive/negative) as the dependent variable. In all 3 models, respondent's HCV status was the primary explanatory variable. Data were analyzed using SPSS v.18 (IBM, Chicago, IL). We did not account for potential variance inflation induced by the RDS design, due to the limitation of the statistical software used; RDS is a relatively new methodology and is not currently incorporated into multivariate procedures available in standard statistical software.

RESULTS

Of the NHBS-IDU2 participants, 9690 respondents self-reported both their HCV status and the HCV status of their last injecting partner. Of all participants, 7270 (75.0%) reported knowing their HCV status and 4128 (56.8%) of those reported HCV positivity. Nearly 47 percent of all participants (n = 4542) reported sharing equipment with their last injecting partner in the previous 12 months, and of those 37.7% (n = 1712) said they were aware of the HCV status of their last sharing partner. The demographic characteristics of participants are shown in Table 1. Approximately 71.8% were male, 21.6% Hispanic, 46.8% non-Hispanic black, and 27.1% non-Hispanic white. Respondents were born between 1930 and 1991, with a mean of 1963 (ie, approximately 46 years of age). About 13.3% of respondents were employed, 57.3% were unemployed, and 24.1% were disabled for work. More than 61% of respondents reported ever being homeless, and 32.1% reported injecting before the age of 18 years.

Association Between Participant's HCV Status and Sharing Equipment With Last Injection Partner

In bivariate analysis, all independent variables, with the exception of injection duration, were significantly associated with participant's equipment sharing behavior (Table 1). Following multivariate adjustment in a multinomial logistic regression, HCV-negative participants, compared to those of unknown HCV status, were more likely to share equipment with an HCV-negative injecting partner vs not sharing (adjusted odds ratio [aOR] 2.0, 95% confidence interval [CI], 1.6-2.6) (Table 2). Similarly, the odds of sharing with an HCV-positive partner, vs not sharing, is increased nearly 5-fold (aOR 4.8, 95% CI, 3.9-6.0) for HCV-positive participants relative to those of unknown HCV status. In contrast, respondents with known HCV status, compared to those of unknown HCV status, were less likely to share with a partner of unknown HCV status vs not sharing (HCV-positive: aOR .8, 95% CI, .7-.9; HCV-negative: aOR .6, 95% CI, .5-.7). Other variables found to be significantly related to injection equipment sharing behavior after multivariate adjustment were gender, race/ethnicity, birth year, education, history of homelessness, employment, and age at first injection (Table 2).

Association Between Participant's HCV Status and Knowledge of Sharing Partner's HCV Status

The results of multivariate logistic regression analysis examining the relationship between participant's self-reported HCV status and knowledge of last injecting partner's HCV status are presented in Table 3. Among respondents who shared injection equipment, those who knew their HCV status were more likely to know their last injecting partner's HCV status compared to those with unknown HCV status: HCV-negative participants (aOR 2.5, 95% CI, 2.0-3.0) were more than 2 times and HCV-positive participants (aOR 4.1, 95%CI, 3.4-4.9) were more than 4 times more likely to have knowledge of their last partner's HCV status compared to respondents who reported an unknown HCV status. Female gender, non-Hispanic white race/ethnicity, educational attainment of high school or more, disabled status, and higher annual income were also positively associated with knowledge of last partner's HCV status. Non-Hispanic black race/ethnicity and history of homelessness were associated with lack of knowledge of last partner's HCV status.

Association Between Participant's HCV Status and Sharing Partner's HCV Status Table 4 shows the results of a multivariate logistic regression model examining the association between participant's self-reported HCV status and last injecting partner's HCV status. Among the respondents who shared injection equipment and reported knowing their last injecting partner's HCV status, HCV-positive persons (aOR 4.6, 95% CI, 3.2-6.4) were nearly 5 times more likely to report their last injecting partner's HCV status as positive relative to persons with an unknown HCV status. By comparison, HCV-negative persons (aOR .4, 95% CI, .3-.6) were 60% less likely to report their last injecting partner's HCV status as positive relative to persons with an unknown HCV status. Non-Hispanic black participants were less likely to report their injecting partner's HCV status as positive compared to Hispanics. Participants with a history of homelessness and those born from 1930 to 1954, respectively, were more likely to report their injecting partner as HCV positive relative to persons who had never been homeless and those born between 1975 and 1991.

DISCUSSION

The strong association between the HCV status of survey respondents and the HCV status of their last injection partner is evidence indicating that PWID are injection equipment serosorting. Our analysis found that PWID are injection equipment serosorting given that study participants were more likely to share injection equipment (IE) with people of concordant HCV status. This outcome corroborates earlier findings demonstrating a correlation between a person's awareness of his/her HCV status and choice of injecting partners [10].

Serosorting is well documented in the literature but largely in the context of HIV risk reduction. Researchers focusing on the sexual choices of MSM [15, 16] have found serosorting is associated with decreased risk of HIV infection [17] and changes in the sexual behavior of MSM when it is employed as an HIV risk-reduction strategy [18]. Serosorting has also been documented among HIV-positive PWID [19]. They have been shown to be more likely to disclose their infection status to other infected persons and more likely to seek out concordant drug-using relationships [12] than HIV-negative persons. HIV-positive PWID in serodiscordant sexual relationships were also found to be more likely to modify their injecting and sexual behavior than participants who were HIV-negative [20] and less likely to engage in less safe drug use and risky sexual behaviors [21]. These findings demonstrate that PWID have the capacity to employ risk reduction behaviors meant to protect their health and that of their injection partners [22, 23].

In this way, serosorting can be applied to drug injection behavior when the act of choosing an injecting partner is based in part on one's own infection status and that of the prospective injecting partner's for the specific purpose of reducing the risk of acquiring or transmitting bloodborne pathogens during an injection episode. Here, serosorting can be categorized as a risk-reduction strategy when the decision to share or not to share injection equipment is influenced by serostatus and enacted by people unable or unwilling to cease injecting drugs, but who nevertheless want to protect their and their injecting partner's health when injecting drugs together. Following this logic, both the act of selecting an injecting partner of concordant infection status and the act of avoiding sharing injection equipment with a person of discordant infection status would be categorized as injecting equipment serosorting [24].

The hepatitis C literature provides a modicum of evidence that knowledge of one's own or another's HCV status can influence how or with whom people inject. One study in Seattle reported PWID were more likely to share injection equipment with the last injecting partner of concordant status [10], while in San Francisco those who perceived their injecting partner to be HCV-positive were found to be less likely to engage in receptive needle sharing [11]; and in Baltimore, HIV-positive participants reported being less likely to injection equipment serosort than HIV-negative participants [12]. The evidence, however, is not entirely positive. Numerous studies show that knowledge of one's HCV status has nominal influence on reducing behaviors that put PWID at risk for acquiring or transmitting blood-borne disease [25-27]. A study of young PWID found no association between HCV-positive status and reductions in less safe injecting practices or choice of injecting partners [28], and another found injecting partners not discriminating based on serostatus and sharing injection equipment just as frequently with sexual partners of concordant and discordant status [29].

This variation notwithstanding, our analysis of the NHBS-IDU2 data establishes a strong association between a survey respondent's knowledge of their HCV status and the selection of an injecting partner. This correlation is deduced from 4 significant findings: (1) a person knowing their HCV status was more likely to know their last injection partner's HCV status; (2) a person knowing their HCV status was less likely to share injection equipment with a partner of unknown HCV status; (3) a person knowing their HCV-negative status was more likely to share injection equipment with a partner that was also HCV-negative; (4) a person knowing their HCV-positive status was more likely to share equipment with a partner reporting an HCV-positive status. These findings suggest that PWID may be serosorting by selectively sharing injecting equipment with persons of corresponding HCV status.

This article is not intended to promote injection equipment serosorting as a HCV risk-reduction strategy for PWID but to report that participants were more likely to share syringes with persons of concordant serostatus. One problem that can be expected if injection equipment serosorting is adopted by PWID is the potential effect of incomplete knowledge of infection status. If PWID know they are anti-HCV positive but mistakenly believe they are infected (when they have actually cleared the virus and are negative for HCV RNA), they could opt to serosort injection equipment with infected persons based on this misunderstanding, placing themselves at risk. This issue highlights the importance of conducting HCV RNA tests for all HCV antibody-positive persons and ensuring that they receive and understand their results.

A similar challenge that arises when PWID serosort by injection equipment is the injecting partner's knowledge of their own HCV status. This requires both accurate knowledge and understanding by the injection partner and full disclosure of their HCV status. Although there are proven effective HIV testing and counseling interventions [30], as well as effective interventions to improve disclosure skills for HIV-positive persons [31], there are no HCV-specific interventions to improve either of these factors. Much can be learned from these established interventions, but HCV test results and counseling messages and disclosure issues require more nuanced communication given the 2-step testing process to determine HCV-infection status and the knowledge needed to understand and disclose that information to injection partners.

This study has some limitations. Unlike several previous studies of serosorting [10], the national data collected through the NHBS-IDU2 study did not include information regarding participants' intention to serosort. It thus remains unknown if the high level of serosorting observed in this study was driven by an intention to do so. Further research needs to be conducted to explore whether intention to serosort is based on the HCV infection status of self and other, and what other factors may be contributing to this behavior. Additional limitations were related to the participant recruitment. The lack of adjustment for the design effect of RDS may have resulted in biased prevalence estimates and artificially smaller standard errors in bivariate analysis; however, there is no consensus on the statistical methods for conducting multivariate analysis [32-37]. Moreover, participants' and their partners' HCV status were self-reported and do not represent actual prevalence, and injecting equipment serosorting behavior is based on participants' perceived HCV status. Future research should thus include analyses of serosorting behavior based on actual vs perceived HCV status. Finally, given the unexplained differences in knowledge of serostatus by gender, race, educational attainment, and homelessness, additional research should be conducted to examine these issues fully.

CONCLUSION

Our analysis of the NHBS-IDU2 data points to the possibility that PWID are serosorting based on knowledge of their and their injecting partners' HCV status. If accurate, the ability to increase PWID's awareness of their HCV status will have important consequences for public health and disease prevention, as it could be an influential element in a person's decision to make health-promoting behavioral changes and their choice of medical treatment. In sum, increasing the proportion of PWID who are aware of their HCV status may contribute to a general increase in the adoption of risk reduction strategies by persons who inject drugs.

Source

Provided by The Fair Pricing Coalition

Posted on December 11, 2013 by admin

The Fair Pricing Coalition (FPC) today condemned Gilead Sciences for the price set for its direct acting antiviral (DAA) Sovaldi™ (sofosbuvir), a once-daily, first-in-class nucleotide polymerase inhibitor approved by the U.S. Food and Drug Administration on December 6, 2013, for the treatment of chronic hepatitis C, including those co-infected with HIV. While FPC believes that all hepatitis C virus (HCV) drugs are priced too high, the coalition of HIV and viral hepatitis treatment activists is especially dismayed by the wholesale acquisition cost (WAC) of $84,000 for a 12-week course of Sovaldi™. For comparison purposes, the FPC notes the 12-week WAC for the recently approved NS3/4A protease inhibitor Olysio™ (simeprevir) is $66,360.

“Sovaldi™ is a very safe and highly effective drug that will significantly shorten HCV therapy and either reduce or eliminate the need for injected pegylated interferon,” explained FPC Co-Chair Lynda Dee. “However, this does not give Gilead unconscionable pricing carte blanche, particularly when considering that Sovaldi™ still needs to be combined with ribavirin for the treatment of HCV genotype 2 for 12 weeks or genotype 3 for 24 weeks. Twelve weeks of therapy with Sovaldi™ plus both pegylated interferon and ribavirin is required for the treatment of HCV genotype 1, the most common genotype in the US, and HCV genotype 4.”

The WAC for 12 weeks of HCV treatment with pegylated interferon and ribavirin is approximately $9,000, resulting in a combined WAC of $93,000 for a Sovaldi™-inclusive regimen to effectively treat a single person living with HCV genotypes 1 or 4. To treat HCV genotype 3, 24 weeks of Sovaldi™ plus ribavirin is required, resulting in a Sovaldi™ WAC of $168,000.

Price Portends an Ominous Future

“Gilead has set the bar dangerously high as other companies determine prices for similar hepatitis C drugs as they enter the market,” Dee said. The effectiveness of Sovaldi™ as a component of future pegylated interferon-free regimens for the treatment of HCV will ultimately depend on co-administration with other DAAs currently in development, and are anticipated to come with their own high price tags.

“Sovaldi™ is expected to transform the curative landscape for hundreds of thousands of people living with hepatitis C in the U.S. who require therapy or responded poorly to previous treatment,” said Lorren Sandt, FPC Co-Chair. “Yet the high price will result in significant barriers to treatment access, particularly in limited and fixed-budget programs, such as Medicare and state Medicaid programs, AIDS Drug Assistance Programs, the Veterans Administration, and in correctional systems.”

The high price may also lead to access challenges imposed by private insurance plans and Qualified Health Plans in the new Affordable Care Act (ACA) Marketplaces, notably those with high co-payment and other out-of-pocket requirements.

“There may be reluctance to add Sovaldi™ to formularies quickly and payers may force people living with HCV to engage in step therapy in which they are first required to try less expensive options that are less effective,” Sandt added. “These options take longer to complete and are associated with serious side effects, which present a serious impediment to adherence and, ultimately, to being cured of hepatitis C.”

Concessions Where They Count

Although Gilead refused FPC’s demand for fair pricing of Sovaldi™, the company has agreed to all FPC requests for concessions regarding Sovaldi™ access programs. These include:

The SupportPath™ (www.mysupportpath.com) patient assistance program (PAP), with a $100,000 maximum income allowance for a household of three and 500% of the federal poverty level (FPL) eligibility criteria for larger households.

  • The SupportPath™ Sovaldi™ co-pay coupon program will provide co-pay assistance for eligible patients with private insurance, including ACA Marketplace exchange patients, who need assistance paying for out-of-pocket medication costs. Most patients will pay no more than $5 per co-pay. Co-pay assistance of up to 20% ($16,000) of the WAC price for Sovaldi™ can also be applied toward prescription deductibles and co-insurance obligations.
  • Gilead has made a contribution to the Patient Access Network (PAN) for co-pay assistance for Medicare Part D clients.
  • Gilead has initiated an emergency Sovaldi™ supply program for patients that may lose their prescriptions.
  • Gilead has agreed to ensure access to its PAP and co-pay assistance programs for AIDS Drug Assistance Program (ADAP) patients who are co-infected with HIV, even in states with ADAP programs that will not include Sovaldi™ on their formularies.

The FPC urges Gilead to widely disseminate the details of its SupportPath™ PAP and co-pay coupon program, which must include providing written SupportPath™ information for prescribers, prominently featured SupportPath™ information in its professional and direct-to-consumer advertisements, and clear links to www.mysupportpath.com via the Gilead and Sovaldi™ websites.

Source

Curr Opin Infect Dis. 2013 Dec 3. [Epub ahead of print]

Karageorgopoulos DE, El-Sherif O, Bhagani S, Khoo SH.

aDepartment of Infectious Diseases/HIV Medicine, Royal Free London NHS Foundation Trust, London, UK bSt. James's Hospital, Dublin, Ireland cResearch Department of Infection, UCL, London dDepartment of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK *Dr Drosos E. Karageorgopoulos and Dr Omar El-Sherif contributed equally to the writing of this article.

Abstract

PURPOSE OF REVIEW: We reviewed the pharmacokinetic interactions between direct-acting antivirals against hepatitis C virus (HCV) and antiretroviral agents.

RECENT FINDINGS: Most relevant pharmacokinetic studies involve healthy individuals and refer to the already licensed HCV protease inhibitors, boceprevir and telaprevir. Data from a phase II clinical trial question the clinical relevance of the interactions between boceprevir and HIV protease inhibitors. The use of a higher dose of telaprevir appears to offset the effect of efavirenz on telaprevir metabolism according to another phase II trial. Boceprevir and particularly telaprevir substantially increase the exposure to maraviroc, similarly to other potent CYP3A4 inhibitors. Different dosages of faldaprevir and daclatasvir have been recommended to be used in combination with a boosted HIV protease inhibitor vs. an efavirenz-based antiretroviral regimen. HIV protease inhibitors appear to substantially increase the exposure to simeprevir. The interactions between sofosbuvir and most antiretroviral agents do not appear to be of clinical relevance or to require dosage modifications.

SUMMARY: The drug-drug interaction studies for HCV direct-acting antivirals and antiretrovirals are important in determining the appropriate drug combinations and dosages. The clinical implications of these interactions need further assessment in different categories of patients, including those with cirrhosis.

PMID: 24305043 [PubMed - as supplied by publisher]

Source

 

J Gastroenterol Hepatol. 2013 Dec 10. doi: 10.1111/jgh.12475. [Epub ahead of print]

Matsuura K, Watanabe T, Tanaka Y.

Department of Virology, Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States.

Abstract

Genome-wide association studies (GWAS) recently revealed that certain interleukin-28B (IL28B) polymorphisms are strongly associated with responses to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy in patients chronically infected with hepatitis C virus (HCV) genotype 1, as well as with spontaneous clearance of HCV. Subsequent reports revealed that IL28B genotypes also affect treatment efficacy in chronic infection with other HCV genotypes. Furthermore, there have been several reports that i implicate IL28B genotypes in inflammatory status, progression of fibrosis and adverse clinical outcomes in chronic hepatitis C (CHC).. Therapy of CHC recently entered a new era with the deployment of direct-acting antivirals (DAAs). These include nonstructural 3/4A protease inhibitors which have shown promise in combination with PEG-IFN/RBV in several clinical trials. IFN-free therapy is expected to be useful especially in IFN-resistant patients and may become the standard of care in the future. Several clinical trials have revealed an association between IL28B genotype and treatment efficacy in triple therapy or interferon-free regimens. On the other hand the mechanism of the effect of IL28B on HCV infection has not yet been elucidated. Recently, it was shown that the polymorphism of IFN-lambda 4 (IFNL4) is in high linkage disequilibrium with that of near IL28B, and more strongly associated with spontaneous or treatment-induced HCV clearance than IL28B genotypes, especially in individuals of African ancestry. This finding provides new insights into the genetic regulation of HCV clearance and its clinical management. IL28B genotyping will be also useful for personalized CHC treatment in the forthcoming era of DAAs.

This article is protected by copyright. All rights reserved.

KEYWORDS: Hepatitis C virus (HCV), direct-acting antivirals (DAAs), genome-wide association study (GWAS), interleukin 28B (IL28B), polymorphism (SNP)

PMID: 24325405 [PubMed - as supplied by publisher]

Source

HCV Treatment: Where We're At, Where We're Going

Medscape Gastroenterology

Rowen K. Zetterman, MD

December 11, 2013

Hepatitis C Today

Worldwide, 170-200 million people, including 3.2-5 million Americans, are infected with hepatitis C virus (HCV). Clinical outcomes of chronic HCV infection include chronic hepatitis, cirrhosis, hepatocellular carcinoma (HCC), and complications of cirrhosis or HCC that result in the need for orthotopic liver transplantation. After liver transplantation, recurrence of HCV infection in the new graft is virtually uniform and can result once again in end-stage liver disease in need of transplantation.

There are 6 major genotypes of HCV, with genotype 1 accounting for 70%-75% of HCV infections in the United States. Genotype 1a is responsible for two thirds and genotype 1b for one third of genotype 1 infections. In treatment studies to date, genotype 1b is less likely to develop viral drug resistance and therefore has a higher treatment cure rate than HCV genotype 1a. Response to treatment is also influenced by the patient's interleukin 28B (IL28B) polymorphism, which results in a greater response in patients with the IL28B CC genotype than in those with IL28B TT genotype.[1]

Where We're At With Treatment

Interferon alpha has been used for 20 years to treat patients with HCV. The mechanism of viral efficacy for interferon has yet to be clearly established. Ribavirin was coupled to interferon therapy in 1998 and has resulted in a doubling of HCV treatment response.[2] Pegylated interferon alpha plus ribavirin has been used since 2001,[3] producing an overall 40% response for treated patients with HCV genotype 1.

Four classes of direct-acting antiviral (DAA) drugs have been developed, including NS3/4A protease inhibitors, NS5B nucleoside inhibitors, NS5B nonnucleoside inhibitors, and NS5A inhibitors.

In 2011, boceprevir and telaprevir, which are NS3/4A protease inhibitors, were approved for the treatment of patients infected with HCV genotype 1.[4,5] Pegylated interferon with ribavirin and either boceprevir or telaprevir is the current standard of care for HCV genotype 1, but this combination is less effective for genotypes 2 and 3. Boceprevir and telaprevir must be administered every 8 hours, and the rapid development of viral resistance prevents them from being used without pegylated interferon and ribavirin.[6,7] The combination of a protease inhibitor plus pegylated interferon and ribavirin results in more anemia and drug interactions than pegylated interferon and ribavirin alone.

The US Food and Drug Administration (FDA) recently approved the protease inhibitor simeprevir with pegylated interferon and ribavirin for the treatment of patients with HCV genotype 1. In addition, the FDA also approved sofosbuvir with pegylated interferon and ribavirin for the treatment of HCV genotype 1, and sofosbuvir and ribavirin for the treatment of HCV genotypes 2 and 3.

Boceprevir and Telaprevir

The current standard of care for HCV genotype 1 is either boceprevir or telaprevir with pegylated interferon and ribavirin. Therapy is 24-48 weeks in duration and results in a sustained viral response (SVR) in 67%-75% of patients. Patients with extended rapid viral response (eRVR) associated with a marked reduction in viral titer by 4 weeks of therapy and HCV absence at 12 weeks may require only 24 weeks of total treatment. Side effects, such as anemia, are frequent, as are drug interactions and medication intolerance.

Some have questioned whether the results of protease inhibitor therapy plus pegylated interferon and ribavirin are actually as good in general use as they were in early trials. A recent evaluation of Veterans Affairs treatment groups found that in similar patients who received either boceprevir or telaprevir, only 50% developed SVR.[8] With current therapy, treatment response is better in previously untreated patients, those with HCV genotype 1b, patients with IL28B CC genotype, and patients without advanced fibrosis or cirrhosis of the liver.

Where We're Going With Treatment

Simeprevir

Simeprevir, a new oral NS3/4A protease inhibitor, was recently approved by the FDA for the treatment of patients with HCV genotype 1 when administered with pegylated interferon and ribavirin.

Two studies (QUEST-1 and QUEST-2) evaluated oral simeprevir 150 mg/day for 12 weeks coupled with pegylated interferon and ribavirin, compared with pegylated interferon and ribavirin alone.[9] In the simeprevir group, 80% of patients had an eRVR at 12 weeks (compared with only 12% eRVR for pegylated interferon and ribavirin alone) and went on to receive 12 additional weeks of pegylated interferon and ribavirin. This resulted in a 91% SVR in the eRVR simeprevir group compared with 21% in other patients, including those treated as long as 48 weeks (QUEST-1). In the second trial (QUEST-2), simeprevir 150 mg/day for 12 weeks coupled with pegylated interferon and ribavirin for 24 weeks resulted in an SVR of 81%, compared with only 50% for interferon and ribavirin alone. No difference in response rates in patients with genotype 1a or 1b were found in this study.

In a third study (PROMISE) of patients in whom previous HCV treatment had failed, patients were treated with 12 weeks of simeprevir and 24 or 48 weeks of pegylated interferon and ribavirin. This study found that those with eRVR who had been treated for a total of 24 weeks had a 79% SVR, compared with 37% in those receiving placebo.[10] Patients with IL28B genotype CC had a 90% SVR, and those with advanced fibrosis had a 77% SVR, but SVR was only 45% in patients infected with HCV containing an NS3 Q80K mutation.

Sofosbuvir

Sofosbuvir, a nucleoside polymerase inhibitor, has been approved by the FDA for treatment of genotypes 1 through 6.

The open-label NEUTRINO trial[11] included patients with genotypes 1, 4, 5, or 6 who were treated with oral sofosbuvir (400 mg daily) and pegylated interferon with weight-based ribavirin for 12 weeks. This resulted in a 92% SVR for genotype 1a, 82% SVR for genotype 1b, 96% SVR for genotype 4, and 100% SVR for the few patients with genotype 5 or 6. Black patients had an SVR of 87%, compared with 91% in Hispanics and Latinos. The treatment response was better in patients with IL28B CC genotype and in those without cirrhosis.

The POSITRON and FUSION trials[12] evaluated sofosbuvir plus ribavirin in patients with genotype 2 and 3 HCV infections compared with placebo plus ribavirin. SVR was observed at 12 weeks of therapy in 78% of patients with previous treatment failure or patients who were previously unable to take pegylated interferon and ribavirin (POSITRON), and at 16 weeks in 73% of patients with previous treatment failure (FUSION). Both studies observed lower response in patients with genotype 3 and in those with cirrhosis.

Sofosbuvir with weight-based ribavirin oral therapy alone has been evaluated in small numbers of patients with HCV genotype 1. In a phase 2 trial of 25 previously untreated patients with all degrees of fibrosis, 68% achieved an SVR when treated with sofosbuvir 400 mg/day plus weight-based ribavirin compared with a 48% SVR in 25 patients treated with sofosbuvir 400 mg plus ribavirin 600 mg daily.[13]The study group included 83% black patients, 23% with advanced liver disease, 70% with HCV genotype 1a, and 48% with a body mass index > 30 kg/m2.

Drugs Under Development

Nearly 40 other drugs are currently under development and evaluation for the treatment of patients with HCV disease. These drugs include faldaprevir,[14,15] ledipasvir,[16] daclatasvir,[17] asunaprevir,[18]danoprevir,[19] alisporivir, and mericitabine, to name a few.

Why Wait to Treat?

Many studies have identified that viral clearance improves overall clinical outcomes of infected patients. In the Veterans Affairs Registry,[20] patients who developed undetectable HCV RNA levels had a 27% reduction in morbidity and a 45% reduction in overall mortality. Thus, it seems evident that we need to develop treatments that are able to clear HCV from all infected patients. Unfortunately, as many as 50% of infected patients do not respond to or cannot tolerate the current standard of care treatment with pegylated interferon, ribavirin, and boceprevir or telaprevir.

Are gastroenterologists and hepatologists currently recommending treating patients with current therapies, or waiting until new drugs become available? A survey of 337 physicians in 2012 found that one half recommended that previously untreated patients with early or minimal fibrosis should be treated with current therapy, whereas 49% recommended waiting for new therapies.[21] For patients who had not responded to previous therapy with pegylated interferon and ribavirin, 74% recommended retreating with the available DAA drugs boceprevir or telaprevir plus interferon and ribavirin, and only 26% suggested waiting for new therapies. Because this survey was completed in March 2012, would those same figures hold today?

Should we treat HCV genotype 1-infected patients who have little hepatic fibrosis with current drugs, such as boceprevir or telaprevir, coupled with ribavirin and pegylated interferon? Arguments in favor of treating now include reasonable success in previously untreated patients, especially those with IL28B CC genotype,[22] recognizing that the response will be reduced in black patients, those with IL28B TT genotype, and those with underlying cirrhosis or high viral loads. On the other hand, waiting means waiting for recently approved medications that appear to have similar efficacy and are associated with less anemia, reduced daily pill numbers, and fewer drug interactions.

Even though response is also reduced with the new drugs in patients with IL28B genotype, overall treatment response with the new drugs seems better than it is with currently available protease inhibitors. Response to simeprevir is affected by the presence of viral Q80K, and it appears that FDA approval will come with a recommendation to consider other treatments for patients infected with the viral Q80K mutation.

What about patients with HCV genotype 1 who have advanced hepatic fibrosis or cirrhosis? Should we be treating them with current protease inhibitors, or should we wait for better therapies? Better side-effect profiles, similar or improved response to treatment with new drugs, the near availability of simeprevir and sofosbuvir for commercial use, and the better response to initial therapy in treatment-naive patients compared with those who have been previously treated suggest that treatment of these patients should be delayed until new drugs are available.[23]

For patients with HCV genotypes 2 or 3, waiting for sofosbuvir seems reasonable. Boceprevir and telaprevir-based treatments have less effectiveness in treating these HCV genotypes. Although we need more data on the treatment of HCV genotypes 4, 5, and 6, preliminary studies to date suggest that the treatment efficacy of simeprevir and sofosbuvir for these genotypes is similar to that of current therapies.

Pursuit of All-Oral Therapy

Will we ever have effective and completely oral therapies for HCV treatment?

For genotypes 2 and 3, that could happen by early 2014, with sofosbuvir plus ribavirin treatment being approved for HCV genotypes 2 and 3. Although patients with genotype 3 are less likely to achieve SVR than those with genotype 2, additional new drugs and studies of combinations of DAAs may further improve SVR for both genotypes.

The meeting of the American Association for the Study of Liver Diseases (AASLD) in November 2013 included several presentations about oral therapy for HCV treatment. A fixed combination of oral sofosbuvir 400 mg and the NS5A inhibitor ledipasvir 60 mg with ribavirin for 12 weeks achieved a 100% SVR in previously treated patients with HCV genotype 1 infection and advanced fibrosis of the liver.[24] Oral sofosbuvir plus ribavirin in patients with HCV and HIV infection (CD4 count > 500 cells/µL) resulted in an SVR of 76% in patients with genotype 1, 88% in those with genotype 2, and 67% in those with genotype 3.[25] A combination of sofosbuvir and simeprevir plus ribavirin for 12 weeks (COSMOS trial) resulted in a 96% SVR in previously treated patients with genotype 1 and a 93% SVR when sofosbuvir and simeprevir were given alone.[26]

These studies suggest that new DAAs and future combinations of DAAs will identify new treatments for FDA approval that will lead to all oral therapies for HCV infection.

Cost Considerations

What of the cost of new DAAs?

Although the pricing of simeprevir or sofosbuvir has not been established, some have suggested that approximately $80,000 per treated patient will be the likely cost for each of these new drugs. How does that compare with the cost of current standard-of-care treatment with pegylated interferon, ribavirin, and boceprevir or telaprevir?

A presentation at the AASLD meeting suggested that the cost of the current standard of care is $189,000 per SVR achieved.[27] In a study of 147 patients, of whom 44% achieved SVR, the direct per-patient costs of telaprevir ($55,273), pegylated interferon ($30,418), and ribavirin ($4926) were supplemented by the additional costs for erythropoietin, transfusions, granulocyte colony-stimulating factor, emergency department visits, and hospitalizations, resulting in a median cost of $83,509 per treated patient. Because SVR was achieved in only 44% of those who were treated, the cost of treatment per successful SVR ($83,509 per treated patient × 2.27, because only 44% of treated patients achieved SVR) was approximately $189,000.

A Future of Improved Treatments

The large number of clinical trials of new DAA drugs to treat HCV infection is encouraging. Simeprevir and sofosbuvir should be available sometime in early 2014, to be coupled with pegylated interferon and ribavirin for the treatment of genotype 1, and sofosbuvir plus ribavirin (but without interferon) for genotypes 2 and 3.

The reduced pill burden, shortened treatment time even with pegylated interferon and ribavirin, similar or improved response rates compared with current protease inhibitor/pegylated interferon and ribavirin therapy, apparent reduction of drug interactions with these newer agents, and somewhat diminished effect of genetic response factors (such as IL28B) all suggest a future of improved treatments for the HCV-infected patient. It seems reasonable that many HCV-infected patients can wait for new drugs to become available.

References

  1. Ge D, Fellay, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment induced viral clearance. Nature. 2009;461:399-401. Abstract

  2. McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998;339:1485-1492.Abstract

  3. Manns MP, McHutchison JG, Gordon SC, et al, and the International Hepatitis Interventional Therapy Group. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965. Abstract

  4. Poordad F, McCone J Jr, Bacon BR, et al; SPRINT-2 investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195-1206. Abstract

  5. Jacobson IM, McHutchison JG, Dusheiko G, et al; ADVANCE Study Team. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405-2416. Abstract

  6. Susser S, Welsch C, Wang Y, et al. Characterization of resistance to the protease inhibitor boceprevir and hepatitis C virus-infected patients. Hepatology. 2009;50:1709-1718. Abstract

  7. Reesink HW, Zeuzem S, Weegink CJ, et al. Rapid decline of viral RNA and hepatitis C patients treated with VX-950: a phase Ib, placebo-controlled, randomized study. Gastroenterology. 2006;131:997-1002. Abstract

  8. Backus LI, Belperio PS, Shahoumaian TA, Cheung R, Mole LA. Comparative effectiveness of the hepatitis C virus protease inhibitors boceprevir and telaprevir in a large US cohort. Aliment Pharmacol Ther. 2014;39:93-103.Abstract

  9. Jacobson IM. Advances in the treatment of hepatitis C virus infection from EASL 2013. Gastroenterol Hepatol (N Y). 2013;9(6 Suppl 3):5-18.

  10. Forns X, Lawitz E, Zeuzem S, et al. Simeprevir (TMD435) with peg-interferon-2a/ribavirin for treatment of chronic HCV genotype 1 infection in patients who relapsed after previous interferon-based therapy: efficacy and safety in patient sub-populations in the PROMIS phase III trial. Hepatology. 2013;58 Suppl:737A-738A.

  11. Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368:1878-1887. Abstract

  12. Jacobson IM, Gordon SC, Kowdley KV, et al; POSITRON Study; FUSION Study. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013;368:1867-1877. Abstract

  13. Osinusi A, Meissner EG, Lee YJ, et al. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA. 2013;310:804-811. Abstract

  14. Sulkowski MS, Bourliere M, Bronowicki JP, et al. Faldaprevir combined with peginterferon alfa-2a and ribavirin in chronic hepatitis C virus genotype-1 patients with prior nonresponse: SILEN-C2 trial. Hepatology. 2013;57:2155-2163. Abstract

  15. Zeuzem S, Soriano V, Asselah T, et al. Faldaprevir and deleobuvir for HCV genotype 1 infection. N Engl J Med. 2013;369:630-639. Abstract

  16. Lawitz E, Poordad F, Hyland RJ, et al. Once daily sofosbuvir/ledipasvir fixed dose combination with or without ribavirin resulted in 95% sustained virologic response in patients with HCV genotype 1, including patients with cirrhosis: the LONESTAR trial. Hepatology. 2013;58 Suppl:315A-316A.

  17. Lok AS. HCV NS5A inhibitors in development. Clin Liver Dis. 2013;17:111-121. Abstract

  18. Suzuki Y, Ikeda K, Suzuki F, et al. Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options. J Hepatol. 2013;58:655-662. Abstract

  19. Marcellin P, Cooper C, Balart L, et al. Randomized controlled trial of danoprevir plus peginterferon alfa-2a and ribavirin in treatment-naïve patients with hepatitis C virus genotype 1 infection. Gastroenterology. 2013;145:790.e.8-800.e.8.

  20. McCombs J, Matsuda T, Tonnu-Mihara I, et al. The risk of long-term morbidity and mortality in patients with chronic hepatitis C: results from an analysis of data from a Department of Veterans Affairs clinical registry. JAMA Intern Med. 2013 Nov 5. [Epub ahead of print]

  21. Chen EY, Lee WM, Hynan LS, Singal AG. A survey of hepatitis C treatment clinical practice patterns using the newly approved protease inhibitors. J Clin Gastroenterol. 2013;47:800-806. Abstract

  22. Shiffman ML, Benhamou Y. Patients with HCV and F1 and F2 fibrosis stage: treat now or wait? Liver Int. 2013;33:105-110. Abstract

  23. Ferenci P. Commentary: triple therapy for patients with chronic hepatitis C and advanced fibrosis? Aliment Pharmacol Ther. 2013;38:1407-1408.

  24. Gane EJ, Stedman CA, Hyland RH, et al. Once daily sofosbuvir/ledipasvir fixed dose combination with or without ribavirin: the ELECTRON study. Hepatology. 2013;58 Suppl:243A-244A.

  25. Sulkowski MS, Rodriguez-Torres M, Lalezari JP, et al. All-oral therapy with sofosbuvir plus ribavirin for the treatment of HCV genotype 1, 2, and 3 infection in patients co-infected with HIV (PHOTON-1). Hepatology. 2013;58 Suppl:313A-314A.

  26. Jacobson IM. SVR results of a once-daily regimen of simeprevir (TMC-438) plus sofosbuvir (GS-7977) with or without ribavirin in cirrhotic and non-cirrhotic HCV genotype 1 treatment-naïve and prior null responder patients: the COSMOS study. Program and abstracts of American Association for the Study of Liver Diseases The Liver Meeting® 2013; November 1-5, 2013. Abstract LB-3.

  27. Bichoupan K, Martel-Laferriere V, Ng M, et al. Real world costs of telaprevir-based triple therapy, including costs of managing adverse events, at the Mount Sinai Medical Center, NY: $195,000 per SVR12. Hepatology. 2013;58 Suppl:329A-330A.

Source

 

Hepatology Research

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Review Article

Masaru Enomoto*, Akihiro Tamori, Yoshiki Murakami, Norifumi Kawada

DOI: 10.1111/hepr.12289

This article is protected by copyright. All rights reserved.

Publication History
Accepted manuscript online: 11 DEC 2013 08:23PM EST
Manuscript Accepted: 6 DEC 2013

Keywords: DAA; direct-acting antiviral agents;  HCV;  hepatitis C;  IFN;  interferon

Abstract

Type I interferons (IFN-α/β), with or without ribavirin, have been the only agents that can eradicate the hepatitis C virus (HCV). An IFN-free regimen combining oral direct-acting antiviral agents (DAAs) will be approved soon for genotype 1 patients. Here we discuss the role of IFN-α/β in the forthcoming “era of DAAs” with consideration of limitations and concerns about IFN-free therapies. First, the therapeutic efficacy of first-generation DAAs varies among the different subtypes. While the rate of sustained virologic response (SVR) is 60–90% among patients with genotype 1b, the rate often falls short of 50% in patients with genotype 1a. IFN and ribavirin can still be indicated for patients with genotype 1a as a platform for combination with DAAs. Second, there is concern about the emergence of drug-resistance resulting from inappropriate use of DAAs. The clinical significance of preexisting resistant variants has not been elucidated. Drug resistance may affect the efficacy of next-generation treatments. An IFN and ribavirin backbone in combination with DAAs is an effective measure to prevent the emergence of drug resistance and/or to suppress preexisting resistant viruses. Third, it remains unknown whether the incidence of hepatocellular carcinoma (HCC) will be reduced in patients who achieve SVR with IFN-free regimens. In contrast, there are many reports in Japan demonstrating the preventive effects of IFN on the development of HCC. When patients do not achieve SVR with first-generation DAAs, low-dose IFN maintenance therapy is a treatment option until the next-generation therapy with pangenotypic potency and high genetic barrier becomes available.

Source

HealthStat Rx: Curing Hepatitis C (HCV) With Confidence

PRESS RELEASE

Dec. 12, 2013, 10:07 a.m. EST

HealthStat Rx puts its leading medication therapy management program to work for millions of HCV patients nationwide to leverage the latest treatments with cure rates up to 90 percent

ATLANTA, Dec 12, 2013 (BUSINESS WIRE) -- One of the nation's leading medication therapy management companies, HealthStat Rx, announces today it offers Sovaldi(TM) from Gilead Sciences and Olysio(TM) from Janssen Therapeutics, to treat chronic hepatitis C virus (HCV) infection in adults.

"FDA studies indicate that the latest HCV treatments, Sovaldi and Olysio, used in conjunction with other antiviral medications, result in cure rates of up to 90 percent after 12 weeks of therapy for patients in certain genotypes," says Vickie Andros, Director of Clinical Services at HealthStat Rx. "What's critical about these HCV cures is that they require careful management of medication delivery to be effective," she says. "That's where HealthStat Rx stands out. Our innovative medication management methodology, with our clinically proven success in working with virology patients is the perfect complement to physicians and healthcare networks that demand HCV success for their patients."

HealthStat Rx's national customer base includes hospitals, clinics, healthcare networks, home health care providers and patients with chronic disease. HealthStat Rx partners with patients and providers to drive superior outcomes. A 2013 medication adherence comparison study showed HealthStat Rx patients had a 35 percent higher adherence rate than that of similar study patients receiving their medications from a retail pharmacy chain. Another recent national study showed patients enrolled in HealthStat Rx's medication therapy management program benefitted from a 60 percent decrease in hospital re-admissions.

"We are excited to be part of this cure and look forward to partnering with doctors and patients who aim to attain optimal cure rates through perfect medication adherence," says Patrick Dunham, HealthStat Rx CEO.

Founded in 2000, HealthStat Rx has evolved into an integral partner in medication and care management for healthcare networks, hospitals, clinics and patients. The company provides services nationwide that maximize its successful medication management methods for numerous chronic diseases including HCV, HIV, diabetes and heart disease.

http://www.healthstatrx.com/index.aspx

ABOUT HEALTHSTAT RX

HealthStat Rx is passionate about improving the lives of millions of chronically ill people through its innovative and comprehensive medication therapy management program. Specially trained pharmacists and patient care coordinators form the foundation of the program and leverage MedPlan(TM), HealthStat Rx's enhanced, in-house EMR. Regular intensive interaction with caring HealthStat Rx professionals supports patients through the daily challenges of living with a chronic condition. HealthStat Rx is recognized as one of America's Fastest Growing Companies by Inc. Magazine. The company was also one of 10 finalists in Microsoft's Excellence in Innovation competition for its development and deployment of MedPlan(TM).

SOURCE: HealthStat Rx

Source

Journal of Hepatology

Article in Press

Minimal Impact of Sofosbuvir and Ribavirin on Health Related Quality of Life in Chronic Hepatitis C (CH-C)

Zobair M. Younossi, Maria Stepanova, Linda Henry, Edward Gane, Ira M. Jacobson, Eric Lawitz, David Nelson, Fatema Nader, Sharon Hunt

Received 17 September 2013; received in revised form 29 November 2013; accepted 4 December 2013. published online 11 December 2013.
Accepted Manuscript

Abstract

Background

Treatment for CH-C contains interferon with substantial associated side effects and health-related quality of life (HRQL) impairment. Currently, there is no published data assessing the impact of interferon-free regimens on HRQL.

Aim

To report the HRQL of patients who participated in clinical trials of sofosbuvir (SOF) for CH-C.

Methods

CH-C patients were treated with sofosbuvir (SOF), pegylated interferon (PEG-IFN), ribavirin (RBV), or placebo in different combinations and duration (POSITRON, FISSION, FUSION, and NEUTRINO phase III trials). HRQL was assessed using SF- 36 at baseline, during, at the end of treatment, and at follow-up, and compared between treatment arms.

Results

HRQL scores decreased over the course of treatment for all treatment arms in all studies; however, patients returned to their baseline score by the end of follow-up. Compared to placebo, SOF and RBV was not associated with HRQL impairment (POSITRON). Compared to SOF and RBV, HRQL was significantly more impaired in the PEG-IFN and RBV arm (FISSION). For those treated with SOF and RBV, there was no difference in HRQL between 12 weeks or 16 weeks of treatment (FUSION). Multivariate analysis demonstrated that depression, fatigue, and insomnia were important predictors of patients’ HRQL prior, during or after treatment. Additionally, anemia and receiving interferon were predictors of HRQL impairment during treatment. Achieving sustained virologic response after 12 weeks of follow-up (SVR-12) with SOF and RBV was associated with improvement in HRQL scores from baseline.

Conclusions

Treatment-related HRQL impairment during SOF and RBV regimen is mild, and does not increase with longer treatment duration. Achieving SVR-12 with SOF and RBV is associated with an improvement in HRQL.

Keywords: Quality of life, Clinical trials, Hepatitis C

logga-top-enkel-se

Stockholm, Sweden—Medivir AB (OMX: MVIR), announces the initiation of a phase IIa trial in chronic genotype 1 hepatitis C infected patients to evaluate the efficacy, safety and tolerability of a 12-week combination therapy of simeprevir, TMC647055 and JNJ56914845, a NS5A replication complex inhibitor.

Study design
Approximately 40 patients will be enrolled in this open-label study to assess the efficacy, safety and tolerability of the co-administration of simeprevir, TMC647055 and two different doses of JNJ56914845 without ribavirin. The trial will evaluate genotype 1a and 1b HCV-infected patients who are either treatment-naïve or who have relapsed after prior treatment with interferon and ribavirin. Patients will receive 75 mg of simeprevir, 30 or 60 mg of JNJ56914845 and 450 mg of TMC647055 plus a low dose of ritonavir as a pharmacokinetic enhancer, each once daily for 12 weeks.

For additional information about this study, please visit www.clinicaltrials.gov

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR, mobile: +46 708 537 292

Medivir is required under the Securities Markets Act to make the information in this press release public. The information was submitted for publication at 08.30 a.m. CET on 12 December 2013.

About Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Medivir and Janssen R&D Ireland for the treatment of chronic hepatitis C infection in combination with other antivirals in HCV genotype 1 & 4 infected patients with compensated liver disease, including cirrhosis.

Simeprevir was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan and in the USA and Canada in November. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.

About TMC647055
TMC647055 is a potent non-nucleoside hepatitis C polymerase inhibitor with broad genotypic coverage. TMC647055 is in phase II clinical development and is developed by Janssen R&D Ireland to treat chronic hepatitis C virus infections. TMC647055 is being investigated in combination with other DAA agents in all oral interferon-free regimens. There have been no treatment-emergent serious adverse events reported in the program.

About JNJ56914845
JNJ56914845, is a potent NS5A replication complex inhibitor. To date phase I and phase II clinical studies conducted demonstrated that JNJ56914845 60 mg once daily is well tolerated and produces rapid, substantial decreases in HCV RNA in treatment-naïve CHC subjects when given alone as a single dose and for 4 weeks in combination with pegIFN and RBV.     

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.com

Source