September 27, 2013

PLOS ONE

Open Access Peer-Reviewed

Research Article

Hisashi Eguchi, Koji Wada

Abstract

Prejudice and discrimination in the workplace regarding the risk of transmission of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) are increased by excess concerns due to a lack of relevant knowledge. Education to increase knowledge about HBV and HCV and their prevention could be the first step to reduce prejudice and discrimination. This study aimed to determine the association between the level of knowledge and negative attitudes toward HBV- and HCV-infected colleagues among the Japanese working population. An online anonymous nationwide survey involving about 3,000 individuals was conducted in Japan. The questionnaire consisted of knowledge of HBV and HCV, and attitudes toward HBV- and HCV-infected colleagues in the workplace. Knowledge was divided into three categories: “ensuring daily activities not to be infected”; “risk of infection”; and “characteristics of HBV/HCV hepatitis”, based on the result of factor analysis. Multiple logistic regression analysis was applied. A total of 3,129 persons responded to the survey: 36.0% reported they worried about the possibility of transmission of HBV and HCV from infected colleagues; 32.1% avoided contact with infected colleagues; and 23.7% had prejudiced opinions about HBV and HCV infection. The participants were classified into tertiles. A higher level of knowledge of HBV and HCV was significantly associated with these three negative attitudes (P for trend < 0.005). This study suggests that increasing knowledge may decrease individuals’ negative attitudes towards HBV- and HCV-infected colleagues. Thus, we should promote increased knowledge of HBV and HCV in stages to reduce negative attitudes toward HBV- and HCV-infected colleagues.

Citation: Eguchi H, Wada K (2013) Knowledge of HBV and HCV and Individuals’ Attitudes Toward HBV- and HCV-Infected Colleagues: A National Cross-Sectional Study among a Working Population in Japan. PLoS ONE 8(9): e76921. doi:10.1371/journal.pone.0076921

Editor: Ranjit Ray, Saint Louis University, United States of America

Received: June 3, 2013; Accepted: September 4, 2013; Published: September 26, 2013

Copyright: © 2013 Eguchi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This study was funded by a Health Labour Sciences Research Grant from The Ministry of Health, Labour, and Welfare (H23-Hepatitis-general-001). The funders had no role in study design, data collection and analysis, the decision to publish, or preparation of the manuscript.

Competing interests: The authors have the following interest. Dr. Eguchi was working as an occupational health physician at KYOCERA Corporation at the time of this study. KYOCERA Corporation is a company producing electronic devices and is not related to medicine for hepatitis. This research is only based on the authors' academic interest as medical doctors. There are no patents, products in development or marketed products to declare. Dr. Wada and Dr. Eguchi did not receive any financial or personal support from KYOCERA Corporation regarding this study. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Introduction

Although the risk of transmission of HBV and HCV through daily contact in the workplace is very low, many patients perceive prejudice and discrimination from acquaintances, family members, and even health care providers [1,2]. Fear of the possibility of transmission, where the perceived risk is often unnecessarily inflated, could also result in unnecessary changes in everyday practices [3]. For patients with HCV, the greatest concern was transmitting the virus to family members [4]. Patients with emerging infectious diseases such as HIV and SARS face problems obtaining a job and perceive unfair treatment in the workplace [5,6]. In Japan, prejudice and discrimination in the workplace also result from the idea that infection with HBV and HCV is misunderstood to be similar to that of HIV [7].

Education to increase public knowledge of a specific disease is often the first step to reduce prejudice and discrimination [8,9]. Targeting inaccurate beliefs about viral hepatitis might improve public health interventions to foster healthier behavior and better hepatitis outcomes [10]. Increasing knowledge of HBV and HCV is effective for preventing the acquisition and spread of infection [11-13]. However, reducing the stigma about HIV/AIDS and mental illness has not always yielded better outcomes [14], [15]. Educational efforts were effective in improving knowledge of HIV/AIDS transmission but these efforts did not convince the general public that HIV/AIDS could not be transmitted through casual contact [16].

It is reasonable to suggest that increasing knowledge of HBV and HCV might reduce negative attitudes towards HBV- and HCV-infected colleagues in the workplace. As far as we are aware, no studies have explored the association between knowledge of HBV and HCV and individuals’ attitudes toward HBV- and HCV-infected colleagues in the workplace. Therefore, the aim of this study was to determine the association between higher levels of knowledge and negative attitudes toward HBV- and HCV-infected colleagues among the Japanese working population.

Materials and Methods

Participants and conduct of the survey

An online, anonymous, self-administered questionnaire was sent to 7,937 individuals in 47 prefectures of 10 areas in Japan in October 2011. Participants were selected randomly from volunteers registered with a survey company, using a stratified sampling method with sex and age. The sex ratio was 1:1, and there were equal numbers of participants in each group.

The cross-sectional survey comprised 28 questions ranging from participants’ demographics (five items), to knowledge of essential factors concerning HBV and HCV (19 items), and general attitudes toward HBV- and HCV-infected colleagues (three items), accompanied by one question related to physical condition. Participants’ demographics information comprised sex, age, educational level, occupation, and individual income.

Demographics and basic characteristics of participants

The demographics and basic characteristics of participants are shown in Table 1. Age was classified into five groups: 20–29, 30–39, 40–49, 50–59 and 60–69 years. Educational level was divided into three categories of lower than or equal to high school graduation; technical college or junior college; and higher than university. Occupation was classified into five groups: regular employee, non-regular employee, unemployed, others, and undergraduates. Others included agriculture, fishery, forestry, and self-employed business owners. Individual income was classified in three equal groups: low, <1 million yen (<12,500 US$); middle, 1–3 million yen (12,500–37,500 US$); and high, >3 million yen (>37,500 US$) (1 US$=80 yen). “Physical condition” was assessed by asking the following question, “How about your health status?” Responses were measured on a four-point scale (1 = very healthy; 2 = relatively healthy; 3 = relatively unhealthy; and 4 = unhealthy), and they were further dichotomized into “very healthy” and “relatively healthy” (= 1) and others (= 0).

Knowledge of HBV and HCV, and general attitudes toward HBV- and HCV-infected colleagues

Knowledge of HBV and HCV was investigated with 19 items that were developed from a discussion based on previous studies [8] [17,18]. Responses were measured on a two-point scale (0= No, I did not know, and 1= Yes, I knew). Table 2 shows each question. Cronbach α was calculated for each factor. We summed each factor, with the greater scores being indicative of having knowledge related to HBV or HCV. The participants were classified into tertiles (low, middle and high) according to the score for each category.

We used the following attitudes toward HBV and HCV infection as the outcome variables of the study: (1) “If I found that people with whom I work were infected with hepatitis virus, I would become anxious that I may be infected too” (

“worrying about transmission”); (2) “If I found that people with whom I work were infected with hepatitis virus, I think I would try not to come in contact with him/her as much as possible” (“avoiding contact with infected colleagues”); and (3) “If I found that people with whom I work were infected with hepatitis virus, I think I would look at him/her erroneously with prejudice, suspecting him/her to be a homosexual, someone who engaged in sexual relationships with an unspecified number of people, or a drug addict” (“Having prejudiced opinions about infected colleagues”). Responses for all three outcomes were measured on a four-point scale (1= I think so; 2= I think so to a degree; 3= I do not really think so; and 4= I do not think so at all), and they were further dichotomized into “I think so” and “I think so to a degree” (=1) and the others (= 0).

Statistical analysis

We assessed factor structures of the three constructs using exploratory factor analysis, whereby all 19 items were entered using the maximum likelihood method. Factors were extracted using common-factors analysis, followed by promax rotation. We named each factor originally based on our discussion.

To explore associations between participants’ knowledge of HBV and HCV and their attitudes toward HBV- and HCV-infected colleagues, each statement of opinion about infected colleagues was treated as a separated outcome. Multiple logistic regression analysis was used to determine the association between level of knowledge of HBV/HCV and the three negative attitudes towards HBV/HCV infected colleagues, where factors included in multivariate analysis were sex, age, educational level, occupation, individual income, and health status. With respect to knowledge of HBV and HCV, the score for each domain was entered into the model. The outcome was not rare; therefore, we applied Zhang’s formula [19].

Statistical analysis was performed using SPSS version 17.0 (IBM, Chicago, IL, USA). A two-tailed value of P < 0.05 was considered significant unless otherwise indicated.

Ethics

This survey was approved by the institutional ethics committee of Kitasato University School of Medicine. Response to the questionnaire was taken as agreement to participate in the study.

Results

Participant demographics and negative attitudes toward HBV and HCV infection

Our recruitment was terminated when the number of participants reached 3,129. Of the 3,129 respondents, 1,549 (49.5%) were male and each age group (20–29, 30–39, 40–49, 50–59, and 60–69 years old) contained approximately 20% of the total number of participants. The sample included 32.3% unemployed persons and 6.7% undergraduate students. Table 1 summarizes the characteristics of the study participants.

In terms of participants’ negative attitudes towards HBV and HCV infection, 1,125 (36.0%) would worry about the possibility of transmission if they worked together with an infected colleague at the same workplace (worrying about transmission); 1,003 (32.1%) would avoid contact with HBV- and HCV-infected colleagues (avoiding contact with infected colleagues); and 742 (23.7%) would have a prejudiced opinion about their HBV- and HCV-infected colleagues (having prejudiced opinions about infected colleagues) (Table 1). “Disagree and strongly disagree” of all three negative attitudes was 56.0%; “Strongly agree and agree” of all three negative attitudes was 17.1% (Table 2).

Individuals’ levels of knowledge about HBV and HCV

Table 3 shows the results of exploratory factor analyses. Three factors were extracted. Factor 1 consisted of six items regarding “ensuring daily activities not to be infected”; Factor 2 consisted of five items regarding “risk of infection”; and finally, Factor 3 consisted of eight items regarding “characteristics of hepatitis”. Cronbach α coefficient was 0.93 for “ensuring daily activities not to be infected”, 0.88 for “risk of infection”, and 0.93 for “characteristics of viral hepatitis”.

By univariate analysis, a high level knowledge of HBV and HCV for each category was significantly associated with worrying about transmission, avoiding contact with infected colleagues, and having a prejudiced opinion about infected colleagues. These associations remained after adjusting for potential confounders by multivariate analysis (Tables 4 and 5). Worrying about transmission was associated with knowledge of HBV and HCV: moderate level [adjusted odds ratio (OR) “ensuring daily activities not to be infected”, “risk of infection”, and “characteristics of viral hepatitis”: 0.74, 0.91, 0.92; 95% confidence interval (CI): 0.66–0.81, 0.83–1.00, and 0.85–0.99; and high level (OR: 0.60, 0.82, and 0.80; 95%CI: 0.54–0.66, 0.75–0.89, and 0.73–0.86). Avoiding contact with infected colleagues was associated with knowledge of HBV and HCV: moderate level (OR: 0.76, 0.76, and 0.88; 95% CI: 0.69–0.83, 0.68–0.83, and 0.81–0.94); and high level (OR: 0.64, 0.54, and 0.79; 95% CI: 0.58–0.70, 0.48–0.60, and 0.73–0.85). Having prejudiced opinions about infected colleagues was associated with knowledge of HBV and HCV: moderate level (OR: 0.90, 0.95, and 0.93; 95% CI: 0.84–0.96, 0.89–1.01, and 0.88–0.98); and high level (OR: 0.87, 0.92, and 0.89; 95% CI: 0.81–0.91, 0.87–0.97, and 0.83–0.94). A higher level of knowledge of HBV and HCV was significantly associated with these three negative attitudes (P for trend < 0.005).

Discussion

This study aimed to evaluate the association between level of knowledge of HBV and HCV and individuals’ negative attitudes toward HBV- and HCV-infected colleagues in the workplace in Japan. We hypothesized that a high level of knowledge of HBV and HCV would be associated with decreasing negative attitudes toward HBV- and HCV-infected colleagues. Our study showed that increasing knowledge of HBV and HCV in each of three categories was associated with decreasing negative attitudes towards HBV- and HCV-infected colleagues.

The level of HBV/HCV knowledge in the Japanese working population was acceptable and in the present study, it was almost the same as in a previous studies of Australian and Chinese health professionals [2] and higher than in the general population [10-12,17,18]. This result indicated that Japanese working population had a relatively high knowledge of HBV/HCV hepatitis.

Knowledge of HBV/HCV was divided into three categories: “Ensuring daily activities not to be infected”, “Risk of infection” and “Characteristics of HBV/HCV hepatitis”. The level of knowledge of “Characteristics of HBV/HCV hepatitis” was lower than the level of knowledge about “Risk of infection” and “Ensuring daily activities not to be infected”. Knowledge of “Characteristics of HBV/HCV hepatitis”, especially “HBV/HCV is the cause of liver cancer in approximately 90% of cases” and “by having hepatitis B or C adequately treated, you may be able to completely cure it, or delay the advancement of cirrhosis or liver” was relatively low. This result is consistent with previous studies [10,11]. The level of knowledge regarding treatment and prognosis of HIV/AIDS was higher than the level of knowledge of HCV [10]. Education to improve knowledge regarding infectious transmission and preventive measures as well as characteristics of hepatitis such as prognosis and treatment should be implemented.

Although HBV/HCV cannot be transmitted through casual contact in the workplace, 20% to 40% of participants had a negative attitude toward HBV/HCV-infected colleagues, 56% of participants did not have all three negative attitudes, and 17% of participants had all three negative attitudes. Negative attitudes towards HBV and HCV infection were evaluated by three items such as “worrying about transmission” (awareness), “avoiding contact with infected colleagues” (behavior) and “having prejudiced opinions about infected colleagues” (discrimination). The percentages of each item were “awareness” (36.0%), “behavior” (32.1%) and “discrimination” (23.7%). In a previous study of HIV/AIDS, “awareness” was more difficult to improve by education compared with other negative attitudes [8]. This may be influenced by inflating the risk of transmission [3]. It might suggest that decreasing negative attitude may be in order of "discrimination", "behavior", and "awareness".

Increasing the level of knowledge regarding HBV/HCV was associated with decreasing negative attitudes towards HBV/HCV-infected colleagues in the workplace. Community-based studies suggest that increasing the level of knowledge of HIV/AIDS and tuberculosis by education leads to a decrease in negative attitudes towards infected patients [15,20,21]. However, even health care professionals with high levels of knowledge regarding HBV/HCV showed discrimination towards hepatitis patients. People living with HIV/AIDS are subjected to stigma, which is significantly associated with organizational cynicism [22]. Thus, both education that provident knowledge and problem solving, learning and interactive educational sessions are recommended [2]. A multidimensional educational approach to increase the awareness of HBV/HCV may be needed in the workplace.

The strength of the present study was that it involved a large sample of more than 3,000 participants from all regions of Japan. Furthermore, the participants had different professions and included homemakers, who are common in Japan, which enabled a wide generalization of the findings. There were some limitations of the study. Our study population presumably had internet access and therefore might have been more aware of HBV and HCV through access to online information [23]. Our study population was educated to a higher level (60% of subjects were university and graduate school) than the general Japanese working population. The study was cross-sectional; therefore, no causal relationship could be concluded from the findings. To clarify the causal relationship between knowledge of HBV/HCV and negative attitudes, an interventional study should be conducted in the future. Although HBV and HCV have different disease characteristics with different dominant modes of transmission and different types and goals of therapy, we did not measure knowledge of HBV and HCV separately. Furthermore, although knowledge of HBV and HCV were probable contributors to attitudes towards HBV- and HCV-infected colleagues, factors influencing their level of knowledge remain unknown. In addition, only some indicators of knowledge regarding HBV and HCV and attitudes towards HBV- and HCV-infected colleagues were investigated.

Conclusion

This study suggests that increasing knowledge may improve individuals’ negative attitudes towards HBV- and HCV-infected colleagues. We should promote increased knowledge of HBV and HCV in stages to reduce negative attitudes towards HBV- and HCV-infected colleagues.

Author Contributions

Conceived and designed the experiments: KW HE. Performed the experiments: KW HE. Analyzed the data: HE KW. Contributed reagents/materials/analysis tools: HE KW. Wrote the manuscript: HE KW.

References

  1. 1. Janke EA, McGraw S, Garcia-Tsao G, Fraenkel L (2008) Psychosocial issues in hepatitis C: a qualitative analysis. Psychosomatics 49: 494-501. doi:10.1176/appi.psy.49.6.494. PubMed: 19122126.
    • 2. Richmond JA, Dunning TL, Desmond PV (2007) Health professionals’ attitudes toward caring for people with hepatitis C. J Viral Hepat 14: 624-632. doi:10.1111/j.1365-2893.2007.00849.x. PubMed: 17697014.
      • 3. Zacks S, Beavers K, Theodore D, Dougherty K, Batey B et al. (2006) Social stigmatization and hepatitis C virus infection. J Clin Gastroenterol 40: 220-224. doi:10.1097/00004836-200609001-00169. PubMed: 16633123.
        • 4. Minuk GY, Gutkin A, Wong SG, Kaita KD (2005) Patient concerns regarding chronic hepatitis C infections. J Viral Hepat 12: 51-57. doi:10.1111/j.1365-2893.2005.00553.x. PubMed: 15655048.
          • 5. Thi MD, Brickley DB, Vinh DT, Colby DJ, Sohn AH et al. (2008) A qualitative study of stigma and discrimination against people living with HIV in Ho Chi Minh City, Vietnam. AIDS Behav 12: S63-S70. doi:10.1007/s10461-008-9374-4. PubMed: 18360743.
            • 6. Lee S, Chan LY, Chau AM, Kwok KP, Kleinman A (2005) The experience of SARS-related stigma at Amoy Gardens. Soc Sci Med 61: 2038-2046. doi:10.1016/j.socscimed.2005.04.010. PubMed: 15913861.
              • 7. Narai R, Oyama T, Ogawa M, Yamaguchi T, Kinaga T et al. (2007) HBV- and HCV- infected workers in the Japanese workplace. J Occup Health 49: 9-16. doi:10.1539/joh.49.9. PubMed: 17314461.
                • 8. Lim VK, Teo TS, Teo AC, Tan KT (1999) HIV and youths in Singapore--knowledge, attitudes and willingness to work with HIV-infected persons. Singapore Med J 40: 410-415. PubMed: 10489510.
                  • 9. Heijnders M, Van Der Meij S (2006) The fight against stigma: an overview of stigma-reduction strategies and interventions. Psychol Health Med 11: 353-363. doi:10.1080/13548500600595327. PubMed: 17130071.
                    • 10. Krauskopf K, McGinn TG, Federman AD, Halm EA, Leventhal H et al. (2011) HIV and HCV health beliefs in an inner-city community. J Viral Hepat 18: 785-791. doi:10.1111/j.1365-2893.2010.01383.x. PubMed: 20950406.
                      • 11. Muñoz Sastre MT, Bacq Y, Mullet E, Sorum PC (2002) Misconceptions regarding hepatitis C in the French public. Prev Med 34: 596-599. doi:10.1006/pmed.2002.1023. PubMed: 12052019.
                        • 12. van der Veen YJ, Voeten HA, de Zwart O, Richardus JH (2010) Awareness, knowledge and self-reported test rates regarding Hepatitis B in Turkish-Dutch: a survey. BMC Public Health 10: 512. doi:10.1186/1471-2458-10-512. PubMed: 20735831.
                          • 13. Chao J, Chang ET, So SK (2010) Hepatitis B and liver cancer knowledge and practices among healthcare and public health professionals in China: a cross-sectional study. BMC Public Health 10: 98. doi:10.1186/1471-2458-10-98. PubMed: 20184740.
                            • 14. Brown L, Macintyre K, Trujillo L (2003) Interventions to reduce HIV/AIDS stigma: what have we learned? AIDS Educ Prev 15: 49-69. doi:10.1521/aeap.15.1.49.23844. PubMed: 12627743.
                              • 15. Corrigan PW, Watson AC, Warpinski AC, Gracia G (2004) Implications of educating the public on mental illness, violence, and stigma. Psychiatr Serv 55: 577-580. doi:10.1176/appi.ps.55.5.577. PubMed: 15128968.
                                • 16. Herek GM, Capitanio JP, Widaman KF (2002) HIV-related stigma and knowledge in the United States: prevalence and trends, 1991-1999. Am J Public Health 92: 371-377. doi:10.2105/AJPH.92.3.371. PubMed: 11867313.
                                  • 17. ul Haq N, Hassali MA, Shafie AA, Saleem F, Farooqui M et al. (2012) A cross sectional assessment of knowledge, attitude and practice towards Hepatitis B among healthy population of Quetta, Pakistan. BMC Public Health 12: 692. doi:10.1186/1471-2458-12-692. PubMed: 22917489.
                                    • 18. Balfour L, Kowal J, Corace KM, Tasca GA, Krysanski V et al. (2009) Increasing public awareness about hepatitis C: development and validation of the brief hepatitis C knowledge scale. Scand J Caring Sci 23: 801-808. doi:10.1111/j.1471-6712.2008.00668.x. PubMed: 19500309.
                                      • 19. Zhang J, Yu KF (1998) What’s the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA 280: 1690-1691. doi:10.1001/jama.280.19.1690. PubMed: 9832001.
                                        • 20. Arikan K, Uysal O, Cetin G (1999) Public awareness of the effectiveness of psychiatric treatment may reduce stigma. Isr J Psychiatry Relat Sci 36: 95-99. PubMed: 10472742.
                                          • 21. Hoa NP, Diwan VK, Co NV, Thorson AE (2004) Knowledge about tuberculosis and its treatment among new pulmonary TB patients in the north and central regions of Vietnam. Int J Tuberc Lung Dis 8: 603-608. PubMed: 15137538.
                                            • 22. Bashir S (2011) HIV/AIDS stigma at the workplace: exploratory findings from Pakistan. SAHARA J 8: 156-161. doi:10.1080/17290376.2011.9724998. PubMed: 23237730.
                                              • 23. Kontos EZ, Emmons KM, Puleo E, Viswanath K (2012) Contribution of communication inequalities to disparities in human papillomavirus vaccine awareness and knowledge. Am J Public Health 102: 1911-1920. doi:10.2105/AJPH.2011.300435. PubMed: 22970692.

                                              Source

                                              Achillion Provides Pipeline Update

                                              logo

                                              September 27, 2013

                                              Conference Call and Webcast to be Hosted Monday, September 30th at 8:30 a.m. EDT

                                              NEW HAVEN, Conn., Sept. 27, 2013 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today provided an update on development of compounds in its pipeline of therapies for the treatment of chronic hepatitis C virus, or HCV. Achillion today received a response from the U. S. Food and Drug Administration, or FDA, on the clinical hold related to sovaprevir, Achillion's NS3 protease inhibitor. The FDA response indicated that, while Achillion's submission addressed all issues noted in the FDA's June 29, 2013 letter, the FDA concluded that the removal of the clinical hold is not warranted.

                                              "While we are disappointed that we were not able to resolve the clinical hold at this time despite having addressed all the issues, we believe the breadth of our portfolio allows us to quickly advance other all oral combination regimens for the treatment of HCV," stated Milind Deshpande, President and Chief Executive Officer of Achillion. "With our Phase 2 NS5A inhibitor, ACH-3102, we are in a position to rapidly initiate combination studies with ACH-2684, our protease inhibitor, with results expected in 2014. Further, we continue to advance our uridine-analog nucleotide, ACH-3422, with which we anticipate initiating clinical trials in the first half of 2014."

                                              ACH-2684 has completed all of the necessary preclinical and clinical trials necessary to support advancement into Phase 2 combination development. Achillion previously reported robust anti-viral activity with ACH-2684 as monotherapy including Phase 1b data in both non-cirrhotic and cirrhotic treatment-naïve HCV genotype (GT) 1 patients. In addition, Achillion will continue to work to resolve the clinical hold related to sovaprevir.

                                              Phase 2 -007 Trial of Sovaprevir and ACH-3102 with Ribavirin

                                              Achillion also announced interim data from the ongoing -007 Phase 2a clinical trial evaluating two doses of sovaprevir, either 200 mg or 400 mg once daily, in combination with 50 mg once daily of ACH-3102 and ribavirin (rbv) twice daily for 12 weeks in patients with treatment-naïve GT 1a or 1b hepatitis HCV.

                                              The Phase 2 trial is a double-blind, placebo-controlled study evaluating the safety, tolerability and efficacy of 12 weeks of sovaprevir, ACH-3102 and rbv in up to 50 treatment-naïve patients with chronic GT 1a or GT 1b HCV. The first segment enrolled 30 patients who were randomized to receive a combination of either 200 mg or 400 mg sovaprevir once daily in combination with a 150 mg loading dose followed by a 50 mg daily dose of ACH-3102, and twice daily doses of rbv, or matching placebos. The primary endpoints for this trial include safety, tolerability, and sustained viral response 4 weeks after the completion of dosing (SVR4). The trial is being conducted at sites in the United States, Canada, New Zealand and Australia.

                                              All patients achieved a very rapid virologic response (vRVR) with HCV RNA less than 25 IU/ml by week 2. Potent efficacy was observed against GT 1b HCV with 100% of patients achieving rapid viral response, or RVR, with HCV RNA levels less than 10 IU/mL at week 4. RVR was achieved in 79% of GT1 patients overall.

                                              To date, the combination of sovaprevir and ACH-3102 with rbv for up to 12 weeks has been well tolerated with no drug-related serious adverse events, no clinically significant changes in vital signs or electrocardiograms. There have been no graded increases in liver function tests, including ALT or AST, for patients receiving active treatment to date. No other laboratory abnormalities were noted with the exception of decreases in hemoglobin observed and attributed to ribavirin.

                                              Conference Call

                                              The Company will host a conference call and simultaneous webcast on Monday, September 30, 2013 at 8:30 a.m. Eastern time. To participate in the conference call, please dial (877) 266-0482 in the U.S. or (631) 291-4567 for international callers. A live audio webcast of the call will be accessible from the Calendar page in the News Center at www.achillion.com. Please connect to Achillion's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

                                              A replay of the webcast will be available on www.achillion.com. Alternatively, a replay of the conference call will be available starting at 11:30 a.m. Eastern time on September 30, 2013, through 11:59 p.m. Eastern time on October 6, 2013 by dialing (855) 859-2056 or (404) 537-3406. The replay passcode is 73738655.

                                              About Achillion Pharmaceuticals

                                              Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's discovery, clinical development, and commercial teams have advanced multiple novel product candidates with proven mechanisms of action into studies and toward the market. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.

                                              Forward-Looking Statements

                                              This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the safety, efficacy and clinical benefits of the combination of sovaprevir and ACH-3102; Achillion's plans and timing for initiating additional combination trials of ACH-3102 and ACH-2684 and ACH-3422; Achillion's development plan; and Achillion's goals and strategies with respect to addressing all types of HCV patients. We may use words such as "expect," "anticipate," "project," "intend," "plan," "believe," "seek," "estimate," and "may" and similar expressions to identify such forward-looking statements. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: satisfactorily respond to regulatory actions with regard to its clinical development programs; replicate in subsequent dose groups and/or later clinical trials positive results observed in the interim data from the -007 combination trial of sovaprevir and ACH-3102, and its other product candidates; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the fiscal quarter ended June 30, 2013 and its subsequent SEC filings.

                                              In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any duty to update any forward-looking statement, except as required by applicable law.

                                              Source

                                              HIV, HCV, and drug use in men who have sex with men

                                              The Lancet, Volume 382, Issue 9898, Pages 1095 - 1096, 28 September 2013

                                              doi:10.1016/S0140-6736(13)62020-6

                                              Copyright © 2013 Elsevier Ltd All rights reserved.

                                              Sean R Hosein a, David P Wilson b

                                              The report by Tony Kirby and Michelle Thornber-Dunwell (July 27, p 295)1 uncovers an emerging and troubling public health and community issue. The intersection of unprotected sex and use of street and party drugs is likely to amplify the transmission of HIV, hepatitis C virus (HCV), and sexually transmitted infections (STI) in men who have sex with men (MSM).

                                              Indeed the latest report from Public Health England indicates that a large increase in HIV incidence is occurring in MSM in London and that there is the potential for growing and harmful interacting epidemics of HIV, HCV, and drug use. The trends documented in London are likely a harbinger of what is happening in communities of MSM in other urban centres in high-income countries.

                                              We have found that in New South Wales, Australia, HIV notifications have increased by 24% in 2012 compared with 2011—predominantly in MSM. Furthermore, 13·1% of people with HIV are co-infected with HCV and 38% of MSM report using recreational drugs in the past 6 months.2, 3

                                              These findings demand that there be renewed, enhanced, and integrated HIV, HCV, and STI surveillance, prevention, and treatment services. Given the complexity of risk factors associated with transmission of HIV and HCV, the copromotion of STI testing and treatment services as well as ways to mitigate the secondary harms of substance use, all need to be coordinated so that overlapping viral disease epidemics can be targeted and contained.

                                              Early diagnosis and treatment is increasingly becoming, or will likely become, the dominant approach to control STIs, HIV, and viral hepatitis. With use of a similar approach for these related infections, it might become more feasible to implement coordinated control strategies that are effective. However, one of the large dangers for which we provide warning is risk disinhibition and primary prevention fatigue, which we are seeing as starting to counteract the benefits of improved access to diagnostic testing and effective treatment.4 In the longer term, research with vulnerable MSM is needed to better understand the range of relevant factors including how these men perceive risk and balance that against pleasure and the causes of the increased incidence of unprotected sex and substance use.5 The results of such research can be used to strengthen the health and wellbeing of communities of MSM around the world.

                                              We declare that we have no conflicts of interest.

                                              References

                                              1 Kirby T, Thornber-Dunwell M. New HIV diagnoses in London's gay men continue to soar. Lancet 2013; 382: 295. Full Text | PDF(145KB) | CrossRef | PubMed

                                              2 Amin J, Kaye M, Skidmore S, et al. HIV and hepatitis C coinfection within the CAESAR study. HIV Med 2004; 5: 174-179. CrossRef | PubMed

                                              3 Hull P, Mao L, Kao S-C, et al. Gay community periodic survey: Sydney. https://csrh.arts.unsw.edu.au/media/NCHSRFile/GCPS_Sydney_2013_Report.pdf. (accessed Sept 10, 2013).

                                              4 Phillips AN, Cambiano V, Nakagawa F, et al. Increased HIV incidence in men who have sex with men despite high levels of ART-induced viral suppression: analysis of an extensively documented epidemic. PLoS One 2013; 8: e55312. CrossRef | PubMed

                                              5 Prestage G, Down IA, Bradley J, et al. Is optimism enough? Gay men's beliefs about HIV and their perspectives on risk and pleasure. Sex Transm Dis 2012; 39: 167-172. CrossRef | PubMed

                                              a Department of Research and Publications, CATIE, Toronto, ON M5V 3B1, Canada

                                              b Kirby Institute, University of New South Wales, Sydney, NSW, Australia

                                              Source

                                              Play 'Tainted' raises spectre of blood crisis

                                              London Community News

                                              September 27, 2013

                                              TORONTO - It's been called one of the worst public health crises in Canadian history — the contaminated blood scandal that left more than 1,000 Canadians infected with HIV and another 30,000 with hepatitis C. Some contracted both.

                                              The majority were hemophiliacs who had been given blood products meant to save their lives, but the treatment turned out to be a death warrant not only for many of them, but also for loved ones whom they unwittingly infected.

                                              "Tainted," a play debuting Wednesday in Toronto, recalls the tragic events through the eyes of a family with three hemophiliac sons who discover they have contracted both deadly diseases from the clotting factor made from contaminated blood.

                                              Written by Kat Lanteigne, "Tainted" is a labour of love for the Toronto-based actor/producer, who was inspired by an extended family member who was infected prior to the overhaul of Canada's blood system and mandatory screening and treatment of blood donations in 1985.

                                              "It had always really haunted me that there was nothing out there in an artistic model to tell the story," says Lanteigne, 38, who began researching the subject 10 years ago, initially with the idea of producing a film, which she was unable to get off the ground.

                                              "And so I realized that if I didn't do something that it was going to be forgotten because it was highly unlikely that people would click onto Health Canada's website and download the Krever inquiry."

                                              That inquiry, led by Justice Horace Krever, began in October 1993 and heard two years of testimony about how the federal and provincial governments, the Canadian Red Cross and others had failed to protect the blood supply.

                                              Krever's November 1997 report found government and the Red Cross had no national blood policy, and that no single authority was accountable for the safety of the blood supply. He also concluded Ottawa had acted too slowly to deal with the threat of blood-borne viruses such as HIV and hepatitis C.

                                              Krever also slammed the Red Cross for failing to recognize the threat and not implementing an adequate screening program. Perhaps most damning was his finding that the agency had chosen to use up supplies of untreated blood products before switching to those heat-treated to kill infectious pathogens.

                                              In fact, 98 vials of untreated blood were sent to Toronto's Hospital for Sick Children, says Lanteigne.

                                              "It's hard for people to wrap their heads around so many people making so many bad choices," she says, stressing the scandal is a part of the country's history that all Canadians need to know about.

                                              "It's really dangerous if we forget stories like the tainted blood crisis and the systemic failings of our system and the level of betrayal that was enacted by our government. Things like that can happen again."

                                              Thousands of Canadians who received tainted blood in the 1970s and '80s eventually died from AIDS or complications arising from hepatitis C, including liver failure from cirrhosis or cancer of the liver.

                                              As a result of Krever's report, responsibility for most of Canada's blood supply was turned over to Canadian Blood Services; Quebec has its own agency, Hema Quebec. In 2004, Ottawa and the provinces announced the first national standards for the quality and safety of the blood system.

                                              Lanteigne interviewed families of hemophiliacs who had died and survivors across the country, and spent two years writing "Tainted," which she describes as a love story.

                                              "'Tainted' is a love story of a family trying to stay intact when the unimaginable happens," she says. The play follows the family as they contend with illness, death and the fight for compensation and justice.

                                              While those infected by contaminated blood did receive some compensation in a controversial agreement with the federal government, three former Canadian health officials, a U.S. pharmaceutical company and one of its former executives were acquitted in 2007 by an Ontario Superior Court judge on charges of criminal negligence.

                                              What struck Lanteigne most when she spoke to families and survivors was "their incredible ability to forgive."

                                              "That really sat with me because the reality is they're all gripped in unyielding grief because they lived with the knowledge that many of those infections could have been prevented. And that part never leaves any of them."

                                              Coincidentally, the play comes at a time when the blood supply is facing another threat, she says. A U.S. company wants to open private clinics in Canada that would pay donors for plasma, an ingredient in certain drugs. The federal government is deciding whether to grant licences for three clinics in Toronto and Hamilton.

                                              News of the would-be clinics was like "kicking dirt in the faces" of those affected by the contaminated blood scandal, says Lanteigne, who has been lobbying with a group of hemophiliacs against their approval.

                                              "The reality is that thousands of people across the country are still living with HIV and hepatitis C because of tainted blood. And Canadians are getting buried all the time," she says of those who continue to succumb to the infections.

                                              She believes the blood system should be managed in the most risk-averse manner possible to avoid history repeating itself, and she hopes her play helps drive home that message to politicians.

                                              "I hope that once (people) have seen this play that they will connect with their elected officials and demand these paid blood donor clinics do not open in Canada."

                                              ———

                                              "Tainted," directed by Dora Award-winner Vikki Anderson, plays at the Aki Studio Theatre in the Daniels Spectrum (585 Dundas St. E) through Oct. 12. Tickets are $27-$42 and available by phone: 1-800-204-0855; online at www.gromkat.com; or in person at the box office.

                                              Note to readers: This is a corrected story. A previous version incorrectly stated the enquiry began in September 2003 and the report was issued in November 2007.

                                              By Sheryl Ubelacker, The Canadian Press

                                              Source

                                              Provided by News-Medical.Net

                                              Published on September 27, 2013 at 5:44 AM

                                              The report by scientists of a new hepatitis virus earlier this year was a false alarm, according to UC San Francisco researchers who correctly identified the virus as a contaminant present in a type of glassware used in many research labs. Their finding, they said, highlights both the promise and peril of today-s powerful -next-generation- lab techniques that are used to track down new agents of disease.

                                              In research published online September 11, 2013, in the Journal of Virology, researchers led by Charles Chiu, MD, PhD, director of the UCSF Viral Diagnostics and Discovery Center, traced the source of the contamination back to tiny diatoms, a type of oceanic algae having nothing to do with human disease.

                                              A scientific team led by researchers from the National Institutes of Health (NIH) first identified the virus as a potential cause of hepatitis in their study of blood samples from 92 people from China who had serious cases of hepatitis not caused by any of the five known hepatitis viruses. Chiu and colleagues discovered the same virus, which they called parvovirus-like hybrid virus (PHV), independently, in a different set of hepatitis patients whose disease was not caused by known viruses.

                                              To further investigate the origin of the virus, Chiu-s UCSF team tracked down its true source by applying next-generation DNA sequencing techniques in a set of carefully controlled experiments, and by referencing the ever-expanding scientific databases that spell out and catalog viral genomes.

                                              -At first we thought this was a genuine hepatitis virus, but later we found it in data sets from patients with many other diseases and even from animals,- said Chiu, a professor of laboratory medicine at UCSF.

                                              The researchers also found that the virus sequenced from samples around the world strangely exhibited almost no genomic diversity. The research team strongly suspected that PHV was a laboratory contaminant and began probing other databases in search of the true source of the virus.

                                              -We did some data mining of environmental databases and found matching DNA sequences from viruses originating in coastal waters off California and Oregon, but not elsewhere- Chiu said.

                                              A developer of sampling and testing technologies may have sourced silica from diatoms in the ocean to make a popular glass column used in the studies, Chiu said. The columns are used to centrifugally spin biological samples to extract nucleic acids - DNA and RNA. Viral DNA that may have once infected the diatoms was also likely extracted as a contaminant during the procedure, along with DNA from biological samples, he said.
                                              -The silica used in nearly all commercial spin columns is derived from the cell walls of diatoms,- he said. -We believe that PHV may be a diatom virus that had inadvertently contaminated the silica-based spin columns during manufacture.- The scientists do not know what caused the cases of hepatitis examined in the studies.

                                              Earlier techniques developed to read out the sequence of DNA building blocks extracted from biological samples permitted the stepwise decoding of genes and eventually the characterization of entire genomes of humans and other organisms.

                                              But in recent years game-changing technological advances referred to as next-generation sequencing have permitted exponentially faster and cheaper sequencing of millions of DNA molecules in a single run through a lab protocol.

                                              These state-of-the-art techniques for piecing together the genomes of organisms from tiny amounts of DNA can be used to efficiently detect pathogens previously unknown to science, but they also are so sensitive that they easily pick up contaminants, Chiu said.

                                              It is not clear why the NIH-led team did not also detect the contaminating DNA in the control samples, Chiu said. Different techniques may have been used in the analysis of control samples in comparison to samples from hepatitis patients, or there may have been lot-to-lot variations in glassware, Chiu speculates.

                                              A similar viral false-alarm scenario unfolded in recent years with a mouse virus called XMRV, first reported in 2006. The virus initially was thought to be associated with human prostate cancer and chronic fatigue syndrome, but last year Chiu and others, including original XMRV co-discoverer Joseph DeRisi, PhD, Howard Hughes Medical Institute Investigator and professor of biochemistry at UCSF, confirmed that XMRV was actually a viral contaminant of laboratory cell cultures and was not present in prostate cancer tissue.

                                              These studies highlight the importance of repeating experiments with good controls to ensure that results are accurate, Chiu said. -Reproducibility is a cornerstone of science, yet far too few studies are validated by follow-up investigation,- he said. Next-generation sequencing is a promising approach to rapidly confirm and validate discoveries of new disease agents, saving investments in time and money that might otherwise be spent pursuing false leads, he added.

                                              Source: University of California - San Francisco

                                              Source

                                              Inactivation of Hepatitis C Virus Infectivity by Human Breast Milk

                                              J Infect Dis. (2013) doi: 10.1093/infdis/jit519 First published online: September 24, 2013

                                              Stephanie Pfaender1, Julia Heyden1, Martina Friesland1, Sandra Ciesek2, Asim Ejaz3, Joerg Steinmann4, Jochen Steinmann5, Angelika Malarski6, Heribert Stoiber3, Georgios Tsiavaliaris7, Werner Bader8, Gerhard Jahreis6, Thomas Pietschmann1 and Eike Steinmann1,*

                                              + Author Affiliations

                                              Abstract

                                              Background. Hepatitis C virus (HCV) is spread through direct contact with blood, although alternative routes of transmission may contribute to the global burden. Perinatal infection occurs in up to 5 % of HCV infected mothers and presence of HCV RNA in breast milk has been reported. We investigated the influence of breast milk on HCV infectiousness.

                                              Methods/Results. Human breast milk reduced HCV infectivity in a dose-dependent manner. This effect was species-specific since milk from various animals did not inhibit HCV infection. Treatment of HCV with human breast milk did not compromise integrity of viral RNA or capsids, but destroyed the lipid envelope. Fractionation of breast milk revealed that the antiviral activity is present in the cream fraction containing the fat. Proteolytic digestion of milk proteins had no influence on its antiviral activity whereas prolonged storage at 4 °C increased antiviral activity. Notably, pretreatment with a lipase inhibitor ablated the antiviral activity and specific free fatty acids of breast milk were antiviral.

                                              Conclusion. The antiviral activity of breast milk is linked to endogenous lipase-dependent generation of free fatty acids which destroy the viral lipid envelope. Therefore, nursing by HCV-positive mothers is unlikely to play a major role in vertical transmission.

                                              Received April 17, 2013. Revision received May 29, 2013. Accepted May 30, 2013.

                                              View Full Text (PDF) Free

                                              logga-top-enkel-se

                                              Stockholm, Sweden — Medivir AB (OMX: MVIR) today reports that Janssen Pharmaceutical R&D Ireland (Janssen) has been informed by the Japanese Ministry of Health, Labour and Welfare (MHLW) that simeprevir has been approved for the treatment of genotype 1 chronic hepatitis C virus (HCV) infection.

                                              "The approval in Japan is a very important step in providing patients with new treatment options. It is the first approval based on the series of global filings that our partner initiated during 2013. Japan is commercially a very exciting market with a huge unmet medical need among hepatitis C patients", says Maris Hartmanis, CEO of Medivir.

                                              The approval in Japan triggers a milestone payment of €5m to Medivir.

                                              Simeprevir, a new direct-acting antiviral agent (DAA), is a protease inhibitor for the treatment of genotype 1 chronic HCV infection. Simeprevir is administered once-daily for 12 weeks as part of a “triple combination” with pegylated interferon and ribavirin followed by an additional 12 or 36 weeks of pegylated interferon and ribavirin alone.

                                              In the CONCERTO clinical trials, simeprevir, as part of a regimen with pegylated interferon and ribavirin, demonstrated strong efficacy, with 89 percent of patients with previously untreated genotype 1 HCV infection achieving a sustained virological response (SVR). The primary endpoint in all clinical studies for simeprevir was a SVR 12 weeks after the last dose of treatment. In studies that included patients who had relapsed after stopping previous HCV treatment, results showed an SVR rate of 96 percent. These results were presented in June at The Japan Society of Hepatology.

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

                                              About hepatitis C in Japan
                                              In Japan, the number of patients with chronic HCV infection is estimated at approximately 1.5 to 2 million. Approximately 70 percent of Japanese patients who have HCV are infected by genotype 1 HCV. After infection with HCV occurs, the infection may persist in about 70 percent of cases, leading to the development of chronic hepatitis. Continued inflammation causes liver fibrosis to develop and progress, potentially developing into liver cirrhosis and liver cancer.[1] Currently, in Japan about 35,000 people are dying from liver cancer every year, and hepatitis C is said to be the cause of liver cancer in about 80 percent of cases.[2]

                                              About simeprevir
                                              Simeprevir is a new DAA (direct-acting antiviral agent), is a protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB for the treatment of genotype 1 chronic hepatitis C infection. Simeprevir works by blocking the protease enzyme that enables the hepatitis C virus to replicate in host cells.

                                              For additional information about simeprevir clinical trials, please visit www.clinicaltrials.gov.

                                              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 pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. 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

                                              References
                                              1. Treatment Guidelines of Hepatitis C in 2012. The Committee for Hepatitis Clinical Guidelines, Japan Society of Hepatology.
                                              2. Latest Statistics on Cancer (2010 Updated Version)" The Center for Cancer Control and Information Services, National Cancer Center.

                                              Source

                                              RenderImage

                                              PRESS RELEASE

                                              Sept. 25, 2013, 4:30 p.m. EDT

                                              - Tybost Facilitates Once-Daily Dosing of the Protease Inhibitors Atazanavir and Darunavir -

                                              FOSTER CITY, Calif., Sep 25, 2013 (BUSINESS WIRE) -- Gilead Sciences, Inc. /quotes/zigman/72849/quotes/nls/gild GILD +1.73% today announced that the European Commission has granted marketing authorization for once-daily Tybost(TM) (cobicistat 150 mg tablets), a pharmacokinetic enhancer that boosts blood levels of certain HIV medicines. Tybost is indicated as a boosting agent for the HIV protease inhibitors atazanavir 300 mg once daily and darunavir 800 mg once daily as part of antiretroviral combination therapy in adults with HIV-1 infection. Today's approval allows for the marketing of Tybost in all 28 countries of the European Union (EU).

                                              "Gilead is pleased to offer HIV patients who rely on protease inhibitors a new boosting option to help facilitate once-daily dosing - an important factor in supporting treatment adherence," said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences.

                                              The EU approval of Tybost is supported by 48-week data from a pivotal Phase 3 study (Study 114), which found that Tybost was non-inferior to ritonavir when administered with an antiretroviral regimen of atazanavir plus Truvada(R) (emtricitabine 200 mg and tenofovir disoproxil (as fumarate) 245 mg) in HIV-infected treatment-naive adults. Approval is also supported by pharmacokinetic data demonstrating that Tybost boosts blood levels of atazanavir and darunavir similar to ritonavir. Tybost should only be co-administered with atazanavir or darunavir.

                                              In Study 114, Tybost was well tolerated and most adverse events were mild to moderate. The most common adverse reactions (incidence greater than or equal to 10 percent, all grades) were jaundice, ocular icterus and nausea.

                                              Tybost is a component of Gilead's Stribild(R) (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil (as fumarate) 245 mg), a once-daily complete single tablet regimen for the treatment of HIV-1 infection that was approved in the United States in August 2012 and in the European Union in May 2013. Gilead submitted a new drug application to the U.S. Food and Drug Administration (FDA) for Tybost as a single agent in June 2012 and received a Complete Response Letter in April 2013. Gilead is working on resubmitting the application to the FDA. Tybost is approved as a single agent in Canada.

                                              About Tybost

                                              Tybost is a cytochrome P450 3A (CYP3A) inhibitor. It boosts blood levels of atazanavir and darunavir by suppressing CYP3A, an enzyme that metabolizes these drugs in the body. Tybost acts only as a pharmacokinetic enhancer and has no antiviral activity.

                                              Indication and Important Safety Information about Tybost

                                              Tybost is indicated as a pharmacokinetic enhancer of atazanavir 300 mg once daily or darunavir 800 mg once daily as part of antiretroviral combination therapy in human immunodeficiency virus-1 (HIV-1) infected adults.

                                              Co-administration with the following medicinal products is contra-indicated due to the potential for serious and/or life-threatening events or loss of therapeutic effect:

                                              * alpha 1 adrenoreceptor antagonists: alfuzosin

                                              * antiarrhythmics: amiodarone, quinidine

                                              * anticonvulsants: carbamazepine, phenobarbital, phenytoin

                                              * antimycobacterials: rifampicin

                                              * ergot derivatives: dihydroergotamine, ergometrine, ergotamine

                                              * gastrointestinal motility agents: cisapride

                                              * herbal products: St. John's wort (Hypericum perforatum)

                                              * HMG-CoA reductase inhibitors: lovastatin, simvastatin

                                              * neuroleptics: pimozide

                                              * PDE-5 inhibitors: sildenafil for treatment of pulmonary arterial hypertension

                                              * sedatives/hypnotics: orally administered midazolam, triazolam

                                              Cobicistat is a strong mechanism-based CYP3A inhibitor and is a CYP3A substrate. Increased plasma concentrations of medicinal products that are metabolised by CYP3A (including atazanavir and darunavir) are observed on co-administration with cobicistat. Higher plasma concentrations of co-administered medicinal products can result in increased or prolonged therapeutic effects or adverse reactions. For medicinal products metabolised by CYP3A these higher plasma concentrations may potentially lead to severe, life-threatening or fatal events. Co-administration of Tybost and atazanavir or darunavir with products that induce CYP3A is not recommended because the resulting levels of cobicistat could be insufficient to achieve adequate pharmacoenhancement of atazanavir or darunavir. Co-administration of Tybost with medicinal products that inhibit CYP3A may decrease the clearance of cobicistat, resulting in increased cobicistat plasma concentrations. Cobicistat is a weak CYP2D6 inhibitor and is metabolised to a minor extent by CYP2D6. Co-administration with cobicistat can increase plasma concentrations of medicinal products that are metabolised by CYP2D6. Cobicistat inhibits the transporters p-glycoprotein (P-gp), BCRP, MATE1, OATP1B1 and OATP1B3. Co-administration of Tybost in patients receiving medicinal products that are substrates of these transporters may result in increased plasma concentrations of the co-administered medicinal products. Unlike ritonavir, cobicistat is not an inducer of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 or UGT1A1. If switching pharmacoenhancers from ritonavir to cobicistat, caution is required during the first two weeks of treatment with Tybost, particularly if doses of any concomitantly administered medicinal products have been titrated or adjusted during use of ritonavir as a pharmacoenhancer.

                                              No dosing recommendations can be made regarding the use of Tybost with oral contraceptives. Alternative forms of contraception should be considered.

                                              Tybost must be co-administered with either atazanavir 300 mg once daily or with darunavir 800 mg once daily. Safety and efficacy have not been established for use of Tybost with either atazanavir or darunavir when used in any other dosing regimen. Antiviral efficacy data from randomized controlled studies is available for cobicistat-boosted atazanavir, but not for cobicistat-boosted darunavir.

                                              Tybost must not be used as a pharmacokinetic enhancer of any other HIV-1 protease inhibitor or any other antiretroviral medicinal product that requires boosting since dosing recommendations for such co-administration have not been established and may result in insufficient plasma level of the antiretroviral medicinal product(s) leading to loss of therapeutic effect and development of resistance.

                                              Tybost co-administered with atazanavir or darunavir should not be used in combination with another antiretroviral agent that requires pharmacoenhancement by means of co-administration with an inhibitor of CYP3A4 to reach the desired therapeutic plasma concentrations (i.e., another protease inhibitor or elvitegravir). Dosing recommendations for such combinations have not been established and co-administration may result in decreased plasma concentrations of atazanavir, darunavir and/or the other antiretroviral agents that require pharmacoenhancement leading to loss of antiviral activity and development of resistance. Tybost should not be used concurrently with ritonavir due to similar effects of cobicistat and ritonavir on CYP3A. Tybost should not be used in combination with other medicinal products containing cobicistat (such as the fixed dose combination tablet elvitegravir/cobicistat/ emtricitabine/tenofovir disoproxil (as fumarate)).

                                              Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine. This effect on serum creatinine, leading to a decrease in the estimated creatinine clearance, should be taken into consideration when Tybost is administered to patients in whom the estimated creatinine clearance is used to guide aspects of their clinical management, including adjusting doses of co-administered medicinal products. Tybost should not be initiated in patients with creatinine clearance less than 70 ml/min if one or more co-administered agent requires dose adjustment based on creatinine clearance (e.g. emtricitabine, lamivudine, tenofovir disoproxil (as fumarate) or adefovir). There are currently inadequate data to determine whether co-administration of tenofovir disoproxil (as fumarate) and cobicistat is associated with a greater risk of renal adverse reactions compared with regimens that include tenofovir disoproxil (as fumarate) without cobicistat.

                                              Cobicistat has not been studied in patients with severe hepatic impairment (Child Pugh Class C). Therefore, the use of Tybost is not recommended in these patients.

                                              Tybost contains the azo colouring agent sunset yellow FCF (E110), which may cause allergic reactions.

                                              About Gilead Sciences

                                              Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.

                                              Forward-Looking Statement

                                              This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the risk that physicians may not see advantages of Tybost over ritonavir and may therefore be reluctant to prescribe the product. In addition, pending marketing applications for Tybost in the United States and other regions may not be approved or approval may be delayed, and marketing approvals, if granted, may have significant limitations on their use. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended June 30, 2013, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

                                              EU Summary of Product Characteristics for Tybost, Stribild and Truvada are available at http://www.ema.europa.eu.

                                              Tybost, Stribild and Truvada are trademarks or registered trademarks of Gilead Sciences, Inc.

                                              For more information on Gilead Sciences, please visit the company's website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

                                              SOURCE: Gilead Sciences, Inc.

                                              Source

                                              Eltrombopag Gets New Hepatitis C Indication in Europe

                                              International Approvals > Medscape Medical News

                                              Megan Brooks

                                              Sep 25, 2013

                                              The European Commission has extended the indication for eltrombopag (Revolade, GlaxoSmithKline) to include adults with chronic hepatitis C virus (HCV) infection with thrombocytopenia severe enough to prevent the initiation or maintenance of optimal interferon (IFN)-based therapy, the company announced yesterday.

                                              The action follows a positive opinion in July for the expanded indication by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA).

                                              The US Food and Drug Administration approved eltrombopag (Promacta) in November 2012 to treat thrombocytopenia in patients with chronic HCV, as reported by Medscape Medical News.

                                              Thrombocytopenia can occur in people with chronic HCV as a consequence of liver damage and is also a common adverse effect of IFN therapy. An estimated 25% of patients with chronic HCV have thrombocytopenia, and up to 9% of patients are severely thrombocytopenic. Patients with thrombocytopenia may be unable to start or continue IFN-based treatment, reducing their chances of achieving a sustained virologic response.

                                              Until now, prescribers in Europe "were without an option for treating low platelet counts in patients with chronic hepatitis C infection" Paolo Paoletti, MD, president of GlaxoSmithKline Oncology, said in a statement.

                                              The new indication for eltrombopag means healthcare professionals in Europe can now use it to help patients "start and stay on interferon therapy, which will facilitate achieving the best outcome for these individuals — that being a sustained virologic response," Dr. Paoletti added.

                                              ENABLE Pivotal Trials

                                              Marketing authorization in Europe was granted on the basis of data from 2 randomized, double-blind, placebo-controlled, multicenter phase 3 studies with a total of 1521 patients with platelet counts below 75,000 µL, the Eltrombopag to INitiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C related Liver DiseasE (ENABLE 1 and 2) trials.

                                              Patients in ENABLE 1 received peginterferon alfa-2a (Pegasys, Genentech) plus ribavirin for antiviral treatment, and patients in ENABLE 2 received peginterferon alfa-2b (Pegintron, Merck) plus ribavirin.

                                              Eltrombopag enabled 95% of patients with chronic HCV-associated thrombocytopenia to achieve platelet counts sufficient for initiation of IFN-based therapy, the company said.

                                              Eltrombopag also enabled more patients to continue receiving IFN-based therapy without dose reduction compared with placebo (45% vs 27%). The drug also allowed roughly 1 in 5 patients who were ineligible or poor candidates for IFN-based therapy resulting form thrombocytopenia to achieve sustained virologic response, the company said.

                                              The most common adverse reactions (experienced by at least 10% of patients) of any grade include headache, anemia, decreased appetite, insomnia, cough, nausea, diarrhea, alopecia, pruritus, myalgia, pyrexia, fatigue, influenza like illness, asthenia, chills, and peripheral edema.

                                              A boxed warning in the United States notes that eltrombopag may cause hepatotoxicity. In addition, in combination with IFN and ribavirin, it may increase the risk for hepatic decompensation. Accordingly, clinicians must regularly monitor serum liver tests. Higher platelet counts with eltrombopag may cause thrombotic and thromboembolic complications.

                                              The most common adverse events reported in the 2 clinical trials included anemia, fever, fatigue, headache, nausea, diarrhea, decreased appetite, and influenza-like illness.

                                              Eltrombopag is also approved to treat thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenia who have not responded sufficiently to corticosteroids, immunoglobulins, or splenectomy.

                                              For the EU summary of product characteristics for Revolade and full US prescribing information, including the boxed warning and medication guide for Promacta please visit the manufacturer's Web site.

                                              Source

                                              HIV/AIDS database adds information from more than 100 countries

                                              OP.0827.hivcartoon.jpg

                                              The U.S. Census Bureau announced that it has updated its HIV/AIDS database with new data for more than 100 countries, including China, Ghana, Ethiopia, India and Cameroon. (Ken Orvidas / For the Times)

                                              By Monte Morin

                                              September 25, 2013, 1:57 p.m.

                                              The U.S. Census Bureau announced Monday that it had updated its world HIV/AIDS database to include new data on more than 100 countries, including China, Ghana, Ethiopia, India and Cameroon.

                                              The update comes as United Nations officials are reporting "dramatic" progress in the fight against HIV/AIDS.

                                              In its annual global report, the Joint United Nations Program on HIV/AIDS said that new HIV infections among children had dropped 52%, while new infections among children and adults had dropped 33%.

                                              The U.S. Census Bureau HIV/AIDS Surveillance Database is a compilation of data from 219 countries or regions, and tracks the prevalence of HIV infection, AIDS cases and related deaths. The primary purpose of the database is to collect and disseminate information from developing countries, and is used by the U.S. Agency for International Development.

                                              According to the database user's guide, the Census Bureau was first tasked with collecting HIV/AIDS data in 1987, when it became clear that the information was readily available to researchers and government organizations.

                                              In 2012, an interactive version of the database was made available online. It does not contain statistics for the United States. Those figures are available through the U.S. Centers for Disease Control and Prevention.

                                              Source