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I n f o r m at i o n , i n s p i r at i o n a n d a d v o c a c y f o r p e o p l e w i t h H I V/A I DS a n d h e pat i t i s C p2 HCV CARE NEWS Newly published US Hepatitis C Treatment Cascade, from the DHHS. HCV CARE NEWS p6 p7 Successful inteferon-free treatment is possible for liver transplant patients. HCV CARE NEWS Interferon-free regimen may be possible for most co-infected individuals. STAFF WRITERS David Evans, Director of Research Advocacy Alan McCord, Director of Education Andrew Reynolds, Hepatitis C Education Manager P. I . p e r s p e c t i v e | SEPTEM B ER 2 0 1 3 | 2 7 3 Ni n t h S t r e e t , S a n F r a n c i s c o , CA 9 4 1 0 3 | w w w . p r o j e c t i n f o r m . o r g Reportback from the 2013 AASLD in Washington, DC In this issue of PI Perspective, Project Inform reports on data that was presented at the annual meeting of the American Academy for the Study of Liver Disease in Washington, DC from November 1–5, 2013, with additional coverage from Infectious Disease Week in October and HEP DART in December. A long journey ahead of us: Ending the silent epidemic of viral hepatitis by Andrew Reynolds, Hepatitis C Education Manager Throughout AASLD 2013, there was significant excitement around the promise that many of the new therapies hold for curing HCV. While these treatments are certainly exciting, the United States has a long way to go to uncover new cases of HCV and link people to medical care. On the final day of the conference, Ronald Valdiserri, MD, Deputy Assistant Secretary for Health, Infectious Diseases and Director, Office of HIV/AIDS and Infectious Disease Policy, delivered a talk entitled “Ending the Silent Epidemic of Viral Hepatitis in the US” where he highlighted the problem of increasing cases of HCV infections, and the challenges of linking to care and successfully treating people once they are diagnosed with the virus. The most recent data presented (2011) shows an estimated 16,500 new HCV infections each year — a 45% increase from 2010. In a sobering comparison, Valdiserri reported the 2010 estimated HCV-related deaths at 16,627. With deaths out-pacing new infections, one might get the false impression of decreases in HCV rates in the United States. A truer picture of HCV in the United States came about when he introduced the “U.S. HCV Treatment Cascade” (figure below). The cascade highlights that only 1.6 million or 50% of the 3.2 million people living with HCV have been diagnosed, with only 1 to 1.2 million or 32-38% of those with HCV referred to medical care. For those who are engaged in medical care, only 220,000 to 360,000 (7-11%) of the total population living with HCV u CONTINUED: page 2 P r o j e c t i n f o r m PERSPECT I VE | SEPTEM B ER 2 0 1 3 | 2 w w w. p r o j ec t i n fo r m .o r g has received treatment for the disease, and only 170,000 to 200,000 (5-6%) has been successfully treated. As HCV therapies improve, it is widely accepted that more patients and medical providers will opt for starting treatment. But as Dr. Valdiserri’s presentation demonstrates, the U.S. must improve its HCV screening and linkage to care infrastructure in order to ensure that all people living with HCV have access to these treatments and wipe out this curable disease. SOURCE: Valdiserri, R. Ending the Silent Epidemic of Viral Hepatitis in the US. AASLD 2013, Washington DC, November 1-5, 2013. U.S. Hepatitis C Treatment Cascade 3.2 MILLION AMERICANS WITH HEPATITIS C (3.2 million Americans living with chronic hepatitis C) 100% 80% 60% 1.6 M 40% 1.0–1.2 M 20% 220,000– 360,000 0% Diagnosed Referred to care Treated 170,000– 200,000 Successfully treated PEOPLE WHO ARE ENGAGED IN HIV CARE SOURCE: Holmberg, et al, “Hepatitis C in the US”, N Eng J Med 2013, 1,859–1,861. P r o j e c t i n f o r m PERSPECT I VE | SEPTEM B ER 2 0 1 3 | w w w. p r o j ec t i n fo r m .o r g 3 A three-drug regimen cures more than 90% of HCV genotype 1 without interferon or ribavirin by Andrew Reynolds, Hepatitis C Education Manager A Phase 2b study of three oral medications taken twice a day achieved an SVR12 in over 90% of people with HCV genotype 1. The regimen includes daclatasvir (DCV), asunaprevir (ASV) and BMS-791325. This study had 166 people included in it: 80 participants who took DCV 30mg, ASV 200mg and BMS-791325 75mg all twice a day, and 86 participants who took the same regimen but took a 150mg dose of BMS-791325. The average age in the study was 54. Men comprised 67% of the participants while 83% were Caucasian and 16% were African American. All of the participants were treatment naïve and all had genotype 1, with 82% having GT 1a. A relatively large number had advanced liver disease: 38% had a fibrosis score of F3 or F4, and 9% had cirrhosis. The IL28B genotype distribution was as follows: 33% CC, 50% CT and 16% TT. (CT and TT do not respond as well to treatment as CC.) The end of treatment response rates for each regimen was very high: 97.5% for the first group taking the 75mg regimen and 94.2% for the 150mg regimen. By patient subgroups, 100% of the cirrhotic patients on the 75mg regimen achieved SVR12, and 91% achieved SVR12 in the IL28B non-CC genotypes. Additionally, 91% of GT1a and 100% of GT1b achieved an SVR12 on the 75mg regimen. Eleven participants experienced virologic failure, and all had GT 1a. There were 6 virologic failures in the 75mg group, of which 2 were viral breakthroughs. There were 5 virologic failures in the 150mg group, with 3 viral breakthroughs. In both groups, the viral relapse occurred before post-treatment week 4. Drug resistance was noted in 17 patients, but 13 of them still achieved an SVR12. Both regimens were well-tolerated: 8 people stopped treatment, although 6 of them came from the 150mg regimen. Lack of efficacy, such as viral breakthrough, occurred in 3 of the 6, while no one in the 75mg regimen experienced a viral breakthrough. The most commonly reported side effects were headaches (25%), diarrhea (15%), fatigue (11%) and nausea (10%). Some lab abnormalities were noted, but none appeared related to the HCV therapy. This regimen marks another advance in the treatment of hepatitis C. Phase III studies of the 75mg regimen in a full-regimen pill have recently begun, and future results will be presented and discussed in scientific conferences and journals. If the results from this larger study prove to be as effective as the one reported here, there will be another option for people with hepatitis C to choose from to get cured, particularly for patients with GT 1a, advanced liver disease, or hard-to-treat IL28B non-CC genotypes. SOURCE: Everson, G., et al. Phase 2b Study of the Interferon-Free and Ribavirin-Free Combination of Daclatasvir, Asunaprevir, and BMS-791325 for 12 Weeks in TreatmentNaïve Patients with Chronic HCV Genotype 1 Infection. AASLD 2013, Washington DC, November 1-5, 2013. P r o j e c t i n f o r m PERSPECT I VE | SEPTEM B ER 2 0 1 3 | w w w. p r o j ec t i n fo r m .o r g 4 New all-oral drug combination holds great promise of high cure rate for hepatitis C genotypes 1a and 1b by Andrew Reynolds, Hepatitis C Education Manager Dr. Eric Lawitz and colleagues reported on the results from the C-Worthy study, which looked at the efficacy and safety of two new Merck drugs with and without ribavirin in three different all-oral regimens. The drugs being studied included MK-5172 (NS3/4A protease inhibitor) and MK-8742 (NS5A replication complex inhibitor). Although it was a small study, the results were very promising with 59 of 60 participants (98%) receiving an SVR12. C-Worthy was broken up into 3 arms, each looking at a specific regimen. Arm 1 had 33 people with genotype 1a or 1b who took 100mg MK-5172 once a day + 20mg MK8742 once a day + ribavirin. Arm 2 had 27 people with genotype 1a or 1b who took 100mg MK-5172 once a day + 50mg MK8742 once a day + ribavirin. Finally, Arm 3 comprised of 13 people with genotype 1b who took 100mg MK-5172 once a day + 50mg MK8742 once a day. All participants had no to mild fibrosis, and no one was co-infected with HIV or HBV. All participants took 12 weeks of therapy. Everyone in arms 1 and 3 reached 100% SVR, while those in arm 2 achieved 96% SVR. (One participant had an HCV viral relapse at week 4 after stopping treatment.) In all cases, the regimens were very well tolerated, and no one stopped treatment due to side effects or adverse events. Nine people who took ribavirin developed anemia, but none so severe as to lead to discontinuation. The most commonly reported side effects were fatigue (26%), headaches (22%) and nausea (18%). For patients with HCV who are seeking a once daily regimen without interferon (and in some cases ribavirin), the results of this study hold great promise. Although further study will be done on these medications — including looking at its effectiveness in individuals with more severe liver disease and those with HIV/HCV co-infection — this regimen may eventually become another effective tool in our fight against HCV. SOURCE: Lawitz, E., et al. High Efficacy and Safety of the AllOral Combination Regimen, MK-5172/MK-8742 + RBV for 12 Weeks in HCV Genotype 1 Infected Patients: The C-Worthy Study. AASLD 2013, Washington DC, November 1-5, 2013. Promising once-daily regimen for treatment hepatitis C genotype 1 by Andrew Reynolds, Hepatitis C Education Manager A new interferon-free regimen of sofosbuvir (SOF) + ledipasvir (LDV) achieved a high cure rate of SVR12 weeks in both treatment naïve and experienced patients with and without ribavirin (RBV). This group also included individuals with cirrhosis, who showed similar treatment responses as those with healthier livers. This marks an exciting point in the development of HCV therapies for both those with earlier treatment failures and those with cirrhosis. The LONESTAR Study included 100 people: Cohort 1 included 60 people who were treatment naïve and did not have cirrhosis while cohort 2 consisted of 40 people who had earlier treatment failures and 50% of whom also had cirrhosis. Within each cohort, patients took ei- ther SOF + LDV or SOF + LDV + RBV for 8 or 12 weeks. Treatment effectiveness and safety, potential drug resistance and drug interactions were all monitored. Study participants were on average 50 years old (21– 73 years) and were 66% male. Most participants were Caucasian, with Hispanic representation at 40% and African American at 9%. The vast majority (87%) had genotype 1a, and 15% had the IL28B CC genotype, who respond better to treatment. At the end of 12-weeks of treatment, 97% achieved an SVR12. All but two in Cohort 1 achieved an SVR12, while in Cohort 2 all but 1 successfully achieved an SVR12. u CONTINUED: page 5 P r o j e c t i n f o r m PERSPECT I VE | SEPTEM B ER 2 0 1 3 Of the 3 people who experienced a viral relapse, none of them took ribavirin. One was also lost to follow-up after week 8. In addition to the 3 treatment failures, drug resistance was detected in several patients: 9% developed NS5A resistance and 70% in the treatment experienced group developed NS3/4a resistance. Two people with NS5A resistance did not achieve an SVR, but all of the others did. Overall, the treatment of SOF/LDV was extremely well tolerated, with no one stopping treatment due to adverse events. Nausea (5%), headaches (5%), and upper respiratory infection (7%) were reported, with no one becoming anemic. In those who took SOF + LDV + RBV, 19% became anemic, and they all experienced similar side effects as the other group but at slightly higher rates. | w w w. p r o j ec t i n fo r m .o r g 5 People living with hepatitis C would benefit from a simple, once-daily regimen that is effective and easy to take with few side effects. Although more research is needed, these early results are very promising and also offer hope for people with cirrhosis and those who were prior treatment failures. SOURCE: Lawitz, E., et al. Sofosbuvir and Ledipasvir Fixed-Dose Combination with and without Ribavirin in TreatmentNaïve and Previously Treated Patients with Genotype 1 Hepatitis C: The LONESTAR Study. AASLD 2013, Washington DC, November 1-5, 2013. COSMOS Study supports interferon-free regimens for hepatitis C genotype 1 by Andrew Reynolds, Hepatitis C Education Manager By the end of 2013 both simeprevir (Olysio, SMV) and sofosbuvir (Sovaldi, SOF) were approved by the FDA. This approval will be for the treatment of HCV genotype 1 together with both interferon and ribavirin. (Note: For treating GT 2 and 3, sofosbuvir was approved with ribavirin only, eliminating the need for interferon for people with these two genotypes.) Although neither drug was submitted to be used together, the COSMOS Study looked at the effectiveness of this regimen for treating GT1 without pegylated interferon. COSMOS is a Phase 2a, randomized, open label study investigating the efficacy of simeprevir + sofosbuvir, taken with and without ribavirin (RBV). Eighty participants were assigned to 2 groups. Cohort 1 included individuals who were prior null-responders (tried treatment but not successful), and Cohort 2 included people who were either new to treatment or prior null responders. Each cohort included people with varying degrees of cirrhosis. Finally, each cohort had different groups of treatment length of 12 or 24 weeks to determine the most effective treatment duration. Cohort 1 was 61.3% male, with an average age of 56. African Americans made up 29% of participants, and another 25% were Hispanic. This cohort included people Metavir scores of F0-1 (41%) and F2 (59%). All had either genotype 1a (78%) or 1b (23%). Additionally, 50% of GT 1a participants had the Q80K genetic mutation (which can negatively impact the effectiveness of simeprevir). Finally, 6% had the favorable IL28B CC genotype, 70% had the CT genotype, and 24% had the TT genotype. Cohort 2 was 67% male with an average age of 58. African Americans made up 9% of study participants, and an additional 17% were Hispanic. This cohort had 46% treatment naïve participants and 54% prior null responders. These participants had more serious liver disease, with Metavir scores of F3 (53%) and F4 (47%). All had either genotype 1a (78%) or 1b (22%). Additionally, 40% of GT 1a participants had the Q80K mutation. Finally, 21% had IL28B CC genotype, 56% had CT and 23% had TT. Everyone in the 12-week groups completed treatment. At the end of treatment all participants had undetectable HCV RNA with no virologic breakthroughs. Within Cohort 1, 96.3% of those on the SMV+SOF+RBV regimen achieved an SVR12, while 92.9% of those on SMV+SOF achieved an SVR12. In Cohort 2, 100% of the treatment naïve participants achieved an SVR12 for both regimens, while 100% of the null responders on SMV +SOF achieved an SVR12 and 93.3% on SMV+SOF+RBV achieved an SVR12 . Participants with non-CC genotypes achieved an SVR12 of 96% on both regimens. Partici- P r o j e c t i n f o r m PERSPECT I VE | SEPTEM B ER 2 0 1 3 pants with a Metavir score of F4 achieved a 100% SVR12 on SMV+SOF, while 91% did on SMV+SOF+RBV. Prior null responders in both treatment regimens achieved an SVR12 of 95%. Both regimens were very well tolerated. No one who took 12 weeks of treatment stopped due to adverse events. The most commonly reported side effects on the SMV+SOF regimen were fatigue (25%), headaches (21%) and nausea (21%). No one from this group became anemic. The results were similar on the SMV+SOF+RBV regimen, with the same side effects reported, though an additional 15% reported a rash and 11% did become anemic. In closing, the results for this study hold much promise for regimens without interferon or ribavirin, offering | w w w. p r o j ec t i n fo r m .o r g 6 hope for those patients who are unable or unwilling to take these medications. We still need to wait for the final analysis, but in the meantime — although this combination is not yet FDA approved — there may still be medical providers willing to prescribe this off-label regimen for their patients. SOURC: Jacobson, I., et al. SVR Results of Once-Daily Regimen of Simeprevir (SMV, TMC435) plus Sofosbuvir (SOFm GS-7977) with or without Ribavirin in Cirrhotic and Non-Cirrhotic HCV Genotype 1 Treatment-Naïve and Prior Null Responder Patients: The COSMOS Study. AASLD 2013, Washington DC, November 1-5, 2013. Successful interferon-free treatment possible for liver transplant patients by Andrew Reynolds, Hepatitis C Education Manager The regimen of sofosbuvir + ribavirin showed very promising early results for treating hepatitis C (HCV) in liver transplant patients. The treatment was well-tolerated, and no drug interactions were seen between the HCV or immunosuppression medications. Interferon-free HCV regimens with few drug interactions are an important clinical development for liver transplant patients. HCV reinfection of a transplanted liver in patients with active disease is a serious health challenge, as the progression to cirrhosis is often rapid and/or the infection can lead to liver graft failure. The current medications for treating HCV can be very challenging to use with immunosuppression drugs, resulting in poor efficacy and significant drug interactions. This small study included 40 patients. All had received a liver transplant, and both treatment naïve and experienced individuals were included. Patients with signs of decompensation or use of corticosteroids (>5mg of prednisone) were excluded. Participants were mostly men (78%, n=31), had an average age of 59, and were mostly Caucasian (85%, n=34). Genotypes 1a, 1b, 3 and 4 were included, and 35 (88%) had been on HCV treatment before. The average time after liver transplant was 4.3 years. Finally, 40% (n=16) had cirrhosis, 35% (n=14) had portal fibrosis, and 23% (n=9) had bridging fibrosis. The 24-week treatment consisted of 400mg sofosbu- vir + 400-1200mg ribavirin (patients started with 400mg and gradually increased based on lab results). Within the first 4 weeks, 100% had undetectable HCV viral loads as did 100% of those who completed (n=39) the treatment at 24 weeks. At four weeks after then end of treatment, 77% maintained an undetectable viral load. The regimen was fairly well tolerated, with 2 patients stopping due to an adverse event. The most common side effects were fatigue (28%), headache (25%), joint pain (23%) and diarrhea (23%). Cough, nausea and anemia were also reported but less often. There were no deaths, graft losses or episodes of rejection reported. An SVR4 of 77% is good news, but it is far too early to determine if these patients are cured. These patients will continue to be observed, and the results will be reported at future conferences. That said, this is an important development in our treatment options for post-transplant patients and offers hope for effective regimens without interferon for this population. SOURCE: Charlton, M., et al. Sofosbuvir and Ribavirin for the Treatment of Established Recurrent Hepatitis C Infection After Liver Transplantation: Preliminary Results of a Prospective, Multicenter Study. AASLD 2013, Washington DC, November 1-5, 2013 P r o j e c t i n f o r m PERSPECT I VE | SEPTEM B ER 2 0 1 3 | w w w. p r o j ec t i n fo r m .o r g 7 New results show an interferon-free regimen may be possible for some co-infected with HIV and HCV by Andrew Reynolds, Hepatitis C Education Manager The interferon-free regimen PHOTON-1 RESULTS of sofosbuvir (Sovaldi) + ribaGenotype # HCV tx On HIV tx HCV SVR 12 Tx failures Relapses virin showed high sustained 1a / 1b 114 24 wks 98% 82% / 54% 1 25 virologic response (SVR) rates for HIV/HCV co-infected in2 26 12 wks 85% 88% 1 0 dividuals in the PHOTON 1 3 42 12 wks 93% 67% 12 12 study. This regimen had no drug interactions with HIV and nausea were the most commonly reported side efmedications, and did not negfects, and one person stopped due to adverse events. atively impact CD4 T-cell percentages. Additionally, the A total of 42 patients with GT3 enrolled, and 93% of treatment was very well tolerated, with very few people them were taking HIV treatment. Within this group, 81% stopping due to side effects or adverse events. of whom were male, 5% were African American and 26% PHOTON-1 is an open-label study that included 223 Latino/a. This group also took 12 weeks of HCV therapy, co-infected persons with HCV genotypes 1, 2 and 3. Inbut only 67% (28/42) reached an SVR. HCV virologic dividuals were given 400mg Sovaldi and a weight-based failure occurred in 12 people during treatment, and HCV dose of ribavirin for either 12 or 24 weeks, depending on viral relapse occurred in another 12 after treatment had genotype and prior treatment history. Nearly all particistopped. Side effects were also similar to the GT2 group, pants were on HIV treatment or had CD4 counts above with 3 people stopping therapy due to adverse events. 500 cells. People with cirrhosis were allowed in this study For all participants, regardless of genotype, no drug but very few enrolled. interactions interfered with either HIV or HCV treatment Among those with GT1, there were 114 participants, effectiveness. There was a small drop in the absolute CD4 98% of whom were on HIV treatment. Among them, 82% count, but this is to be expected with ribavirin. There was were male, 33% African American, and 22% Latino/a. no change in CD4 cell percentage. Two individuals deThese participants were given 24 weeks of sofosbuvir + veloped detectable HIV viral load, but in both cases poor ribavirin and 76% (87 of 114) achieved an SVR12. adherence to HIV treatment was the cause. It is important to further distinguish these results With all of the advances in HCV therapies, we still need by sub-type: GT1a had an SVR of 82% while GT1b was to find safe and effective regimens for co-infected persons. 54%. For both GT 1a and 1b, HCV on-treatment failure With interferon-free regimens on the horizon for HCV mowas limited to 1 person, while 25 people had an HCV vino-infected persons, this study showed comparable results ral relapse after treatment. Treatment was generally very for co-infected persons. Side effects were minimal, drug inwell tolerated with fatigue, nausea and headaches most teractions were not a problem, and CD4 counts were only commonly reported. Three people had to stop HCV treatmildly affected. This marks an exciting development in the ment due to adverse events. treatment of HCV in people living with HIV. Among those with GT2, 85% of the 26 people were taking HIV treatment. As for demographics, 81% were SOURCE: male, 23% African American and 31% Latino/a. These Sulkowski, M., et al. All-Oral Therapy with Sofosbuvir participants took 12 weeks of HCV treatment and 88% Plus Ribavirin for the Treatment of HCV Genotype (23/26) reached an SVR12. The on-treatment HCV viro1,2, and 3 Infection in Patients Co-Infected with HIV logic failure was limited to 1 person, and no one experi(PHOTON-1). AASLD 2013, Washington DC, November enced an HCV relapse after treatment. Fatigue, insomnia 1-5, 2013. P r o j e c t i n f o r m PERSPECT I VE | SEPTEM B ER 2 0 1 3 | w w w. p r o j ec t i n fo r m .o r g 8 Treating hepatitis C in HIV/HCV co-infected people: A new option on the horizon by Andrew Reynolds, Hepatitis C Education Manager A new HCV protease inhibitor faldaprevir, used together with pegylated interferon + ribavirin, showed a high 4-week sustained virologic response (SVR4) of 74% in HIV/HCV co-infected people. These are early results and therefore may change as people are again tested at 12 weeks. These results offer hope for a more effective treatment of HCV in co-infected people. Approximately 300,000 people are co-infected with HIV and HCV, who are at risk for a more rapid liver disease progression and end-stage liver disease. (HCVrelated liver disease is the leading cause of non-AIDS related deaths.) To date, the FDA-approved treatment options have been limited to using pegylated interferon (PI) + ribavirin (RBV) or the off-label use of Incivek or Victrelis + PI + RBV. (Note: at press, Sovaldi has received FDA approval for treatment of HCV in co-infected individuals.) Entitled “STARTVerso4”, this is one of a series of studies looking at the effectiveness of faldaprevir in various populations and together with other HCV medications. This phase 3 study included 308 co-infected people; most of whom were men (81%) and Caucasian (83%). Average age was 47. All participants had either HCV genotype 1a (79%) or 1b (21%). Most participants (85%) did not have cirrhosis but in those who did, 29% had advanced fibrosis (F3/F4). Finally, 78% were treatment naïve for HCV, most were on HIV treatment, and only 4% had never taken HIV meds. The overall SVR4 for this study was 74%, and it was evenly distributed between genotype 1a (74%) and 1b (77%). For those without cirrhosis 74% achieved an SVR4 while 77% of those with cirrhosis achieved an SVR4. It is also noteworthy that 87% of individuals who did not respond to earlier treatment achieved an SVR4 (compared to 71% of those who were treatment naïve). The SVR4 were achieved in a fairly even distribution across various HIV treatment regimens ranging from 67–80% (including an SVR4 of 73% in those not on HIV meds). Researchers concluded that the HIV meds used did not have significant drug interactions. While nearly all participants (98%) experienced a medication side effect or adverse event, only 1% of people had to stop faldaprevir while 7% had to stop all medications. The most commonly reported side effects were nausea (37%), fatigue (34%), diarrhea (27%), headache (25%), loss of strength (23%) and loss of appetite (21%). Additionally, 44% of participants were given a grade 3 or higher abnormality on blood work. As we fully enter the era of “Directly Acting Antivirals”, we are witnessing significant advances in HCV therapies, with many more HCV drugs on the horizon for people living with HIV. That said, most of these drugs have only been studied in mono-infected persons. With this and many other studies underway, the hope is that HIV/HCV co-infected people will be able to reap the same benefits from HCV treatment as mono-infected persons. SOURCE: Rockstroh, JK, et al. STARTVerso4 Phase III Trial of Faldaprevir plus Pegylated Interferon and Ribavirin in Patients with HIV and HCV Genotype 1 Co-Infection. AASLD 2013, Washington DC, November 1-5, 2013. P r o j e c t i n f o r m PERSPECT I VE | SEPTEM B ER 2 0 1 3 | w w w. p r o j ec t i n fo r m .o r g 9 Other conference coverage: HEP DART and ID WEEK by Andrew Reynolds, Hepatitis C Education Manager Several conferences were held in the last few months of 2013 that were relevant for treating and care of hepatitis C: Infectious Disease Week (October), AASLD (November), and hepDART (December). There were a variety of important presentations throughout, and the following offers a review of some of the highlights from these three conferences. CONFERENCE: HEP DART 2013 This annual conference has been convening since 1995 and describes its mission as follows: “The focus of HEP DART 2013 is to assemble clinicians, researchers and basic scientists together to advance our knowledge of the ongoing drug development processes in the treatment of hepatitis B and hepatitis C and other viruses affecting the liver, including co-infections with HIV. HEP DART 2013 will uniquely blend the areas of biology, chemistry, pharmacology and clinical research to provide the scientific community with an increased understanding of the current and future challenges in therapeutics for hepatitis infection.” There were a wide array of presentations on both HCV and HBV, but we choose to focus on 3 presentations that address the epidemiology and needs of people are risk for or living with HCV who are often forgotten: people who inject drugs (PWIDs) and people in prison. Addressing Health Disparities in HCV: The “Forgotten Populations” In August 2012, the CDC released recommendations for screening HCV infection in people born between 1945 and 1965 — so-called “baby boomers”. Initially, the United States Preventative Services Task Force did not endorse these recommendations, but a concerted effort from advocates helped to overturn that decision. Lost in the excitement of these recommendations was the fact the USPSTF also endorsed the screening of HCV in “risk-based populations”: PWIDs, non-injection nasal drug-users, and prisoners. Dr. Mark Sulkowski of Johns Hopkins University School of Medicine delivered a provocative presentation entitled the “Forgotten Populations” reminding us of the other people who at risk for or living with HCV, as well as other subgroups with special needs in the US. The global burden of viral hepatitis is high: hepatitis B and C deaths are slightly less than those of HIV, but on par with malaria, road accidents and non-HIV related tuberculosis. In low and middle income countries, particularly in the Middle East and Southeast Asia, the burden of HCV is high and often in genotypes that have not been typically addressed by the pharmaceutical industry. Genotype 3 and 4 are more common in these countries than they are in high income countries, but research for them and available treatments are lacking. By contrast, for example, while much research and development has occurred for treating and curing HCV GT1 (the most common in the US and Europe), and we are seeing cure rates in the 90-100% range, with shorter duration of treatments and fewer side effects. In the US, HCV screening in HIV-infected persons — and now in those born between 1945 and 1965 — are recognized and practiced routinely. Sulkowski lists the following populations as “forgotten”: prisoners, persons who inject drugs, African Americans, persons born after 1965 and persons born before 1965. Sulkowski notes that even in areas where it is widely recognized that HCV disease is a significant burden, such as in PWIDs, there are limited options for screening, care and treatment. Similarly, while it is widely accepted that the burden of HCV falls disproportionately among African Americans, health disparities in this population continue. Dr. Sulkowski highlighted the importance of screening for HCV in pregnant women citing the fact the USPSTF will not recommend routine screening for this population because there is no intervention that has been shown to reduce the risk of transmission from mother to infant. Rates of mother-to-child transmission are around 4.3%, and it is estimated that between 10,000 and 60,000 babies will be infected with HCV each year. Treatment as prevention in this population may be an option as we are now in an era where ribavirin — a drug that is contraindicated for pregnancy — is unnecessary. More research is needed, but the early results of safety testing of sofosbuvir have been promising in animal modeling. Dr. Sulkowski’s presentation also highlighted an emerging problem in HCV: A rise of infections in non- P r o j e c t i n f o r m PERSPECT I VE | SEPTEM B ER 2 0 1 3 urban youth who inject drugs. We have seen reports in Massachusetts and New York of outbreaks of acute HCV infections in this population. These youth often begin with prescription opioid use and move on to injecting heroin. There are limited services targeting this group, and as HCV is often asymptomatic these new infections often go unrecognized and other transmissions occur as they share injecting equipment. As we move further into the era of direct acting antivirals, treatment as prevention may also serve us in this population as well. All oral, interferon-free treatments that are easy to take, have fewer side effects and shorter duration can open up the HCV treatment landscape for people who are actively using drugs, or who have recently quit use. Finally, Dr. Sulkowski highlighted the need to screen and treat those who were born before 1945, and therefore fall outside the baby-boomer birth cohort recommendations. People in this age group have similar risk factors, and comparatively higher rates of HCV infection than the general population. Additionally, due to their age, they are at great risk of developing end-stage liver disease such as liver cancer. Earlier research has shown that older individuals respond to treatment as well as do younger ones, and as we have easier treatments in the future, this trend should continue. A one-time HCV screen for this population is an important intervention to mitigate the suffering caused by liver cancer and other end-stage liver disease. This presentation highlights that while we have made much progress in the advancement of HCV treatments, we have far to go in the arena of screening and linkage to care and treatment. Similarly, we must do a better job of preventing HCV in vulnerable populations such as young people who inject drugs, as well as in mother-to-child transmission. The hope is that with these newer, easier to take treatments, these populations will have their needs met; but public health officials, clinicians and advocates must stay vigilant and not assume that this will happen without effort. SOURCE: Sulkowski, M. Forgotten Populations (Hepatitis C). HEP DART 2013. Big Island, Hawaii, December 8-12, 2013. | w w w. p r o j ec t i n fo r m .o r g 10 Breaking Down the Barriers to HCV Treatment among People Who Inject Drugs Treating hepatitis C in people who inject drugs (PWID) is a very important issue, yet it remains a very controversial one among many in the public health and medical communities. In this presentation, Jason Grebely of the University of New South Wales, Australia, provides a broad overview of this issue and demonstrates the importance of reaching this population, as he writes “PWID are the core of the HCV epidemic and ‘aging cohorts’ of PWID will lead to considerable advanced liver disease burden.” PWID make up about 80% of new infections and 60% of all infections overall, and HCV is a leading cause of death in this group. Grebely shows us that 80% PWID are willing to do HCV treatment, yet only 1-2% per year receives treatment. He reviews a number of barriers at three distinct, but inter-related levels: systems, provider and patient. At a systems-level there is limited infrastructure for the screening, care and treatment of PWID, a lack of standard recommendations for screening and treatment, and in some case, no or limited mechanisms to cover the cost of treatment. Providers have concerns about treating PWID due to fears of poor adherence to treatments, inability to manage side effects, or risk of reinfection if successfully cured. Finally, patients are hampered by competing priorities of substance use and other basic survival needs (housing, employment, etc) as well having limited knowledge of HCV, including understating the seriousness of the disease. In spite of these barriers, Grebely’s presentation reviewed 36 academic papers and found high rates of sustained virologic response (SVR, the term used to describe a cure for HCV) in a number of studies, and an SVR rate of over 55% overall (with the treatment standard of care on pegylated interferon and ribavirin). Certainly treatment is not easy, and Grebely reviews strategies to improve HCV screening, assessment and treatment for PWID, among them access to point of care rapid HCV testing, enhanced education programs, participation in support groups and a multidisciplinary approach to HCV treatment. Finally, Grebely closes with a discussion of the broader, public health impact of treating PWID: Treatment as prevention. Estimates suggest that as we scale-up treat- P r o j e c t i n f o r m PERSPECT I VE | SEPTEM B ER 2 0 1 3 ment for PWID, we will not only reduce the prevalence of HCV (that is, the number of people living with the disease), but we will also see a decrease of HCV incidence (that is, of new HCV infections). This has implications in a variety of settings, including jails and prisons, as treating populations who are most at risk will significantly lower new infections in the future. SOURCE: Grebely, J. Breaking Down the Barriers to HCV Treatment among People Who Inject Drugs. HEP DART 2013. Big Island, Hawaii, December 8-12, 2013. HCV Treatment in Prisons Just as reaching and treating people who inject drugs will be vital to addressing HCV in the US, so too will reaching and treating people in jails or prisons. The US has the largest prison population in the world, and most have a history of substance use. Overall, 17% of inmates in US jails or prisons are HCV antibody positive, with 12% chronically infected — although only about 25% are aware of their infection. It is estimated that over 1 million people with HCV come into contact with the US criminal justice system each year. Indeed, incarcerated people represent as many as 1/3 of the US HCV-infected population. Liesl Hagan, an MPH student at Emory University, presented on the cost effectiveness of treating people in prison in the era of direct acting antivirals. Previous studies have shown that interferon-free HCV regimens are cost-effective when compared to the previous standard of care in the community. Hagan based her cost-effectiveness analysis of treating in prisons based on the cost of treatment and the benefits of such treatment using a measure called “Quality Adjusted Life Years” (QALYs). She found that treating people in prison with interferon-free therapy was more cost effective than in the community. The cost effectiveness increased further when younger prisoners were treated, and if/when HCV drug prices go down the cost effectiveness increases further. These are important findings for public health officials and prisoner health advocates. Treating prisoners with HCV has important public health implications and can cure up to 1/3 of people living with HCV. Hagan con- | w w w. p r o j ec t i n fo r m .o r g 11 cludes her presentation with a call to “invest in high-risk, high prevalence populations” with the impact of not only improving prisoner health, but reducing the risk of transmission both within the prison system itself, and the communities in which people in prison will eventually return. SOURCE: Hagan, L. Optimizing Cost-Effectiveness of All-Oral Hepatitis C Treatment in Prison Settings. HEP DART 2013. Big Island, Hawaii, December 8-12, 2013. CONFERENCE: ID Week ID Week is a relatively new conference that brings together infectious disease specialists and researchers from a wide array of disciplines and interests. Hepatitis C was featured in a variety of presentations, and we highlight two of them here. HCV Deaths Severely Under-represented in the United States Official statistics state that between 2.7 to 3.9 million people are living with chronic hepatitis C (HCV), making it the most common blood-born infection in the US, and a leading cause of death and liver transplants. However, there are many who think our knowledge of the true number of people living with HCV is severely under-reported, as is our knowledge of the actual number of deaths related to this disease. Following a review of data from the Chronic Hepatitis Cohort Study (CHeCS), Reena Mahajan and colleagues conclude that HCV-related deaths are indeed grossly under-reported and the mortality rate for people infected with HCV is 12 times higher than that of the general public. The authors looked at 11,703 patients in CHeCS, a longitudinal observational cohort study of over 2.1 million people infected with chronic HCV. Within this group, 1,590 HCV patients died during the study period, 2006 to 2010. At the same time they compared these deaths with the deaths of 12 million people from the “Multiple Cause of Death”. In their analysis, the authors found that HCV listed as the cause of death was extremely low and leads to an P r o j e c t i n f o r m PERSPECT I VE | SEPTEM B ER 2 0 1 3 underestimation of the actual cause of death in many people living with HCV. Even among the 1,590 patients in CHeCS who died during the study period, only 19% had HCV listed on their death certificate. Overall 16,622 people had HCV listed on their death certificates in 2010, the actual number was more likely to be over 80,000. The mortality rate from HCV was 12 times higher than that of the general population. The mean age of death in people with HCV was 59 years, while that of the general population was 74. As we enter the era of “direct acting antivirals”, we have the potential to dramatically reduce the number of deaths from hepatitis C. This study highlights the need for effective screening, identification and treatment of HCV in order for the United States to reduce the burden of disease and suffering caused by hepatitis C. SOURCE: Mahajan, R., et al. Mortality among Persons in Care with Hepatitis C Virus Infection-Chronic Hepatitis Cohort Study (CHeCS), 2006-2010. ID Week, 2013, San Francisco, CA. October 2-6, 2013. Referral and Treatment Patterns of Chronic Hepatitis C Screening and linkage to care can be a challenge for people with HCV, and this poster presentation illustrates some these challenges, but also points to potential successes. In a retrospective cross-sectional study looking at HCVinfected persons in a community-based clinic, Dr. Wei B. Ooi and colleagues found that 215 of 235 (92%) of patients | w w w. p r o j ec t i n fo r m .o r g 12 who test positive for HCV were referred to a hepatitis specialist. The authors hypothesized that this was due to an integrated electronic medical record and a sharing of some staff across programs. The success of the referral, however, did not lead to immediate linkage to care or HCV treatment. Out of these 215 patients, only 146 (68%) saw a specialist and only 26 of these individuals (18%) received treatment. Additionally, the average time from referral to actually seeing a specialist was 411 days, and the average time of referral to treatment was 226 days. The authors found several facilitators and barriers to care. Among the facilitators, those who were co-infected with HCV and HIV, had other non-HCV related morbidity, or were married were more likely to receive earlier HCV care. The barriers included active substance use, mental health disorders and/or patient preference to defer care. The authors conclude that the low rate of treatment initiation is the result of a complex array of patient, provider and/or system factors. This is a very important study that highlights a vexing problem for HCV: Even as we are advancing the HCV treatment landscape to include simpler, shorter and more effective medications, we still have far to go with screening and linkage to care. Further research into effective techniques and methods of referral and linkage will add to our understanding of the complexities of engaging HCV-infected patients into medical care and should be prioritized going forward. SOURCE: Ooi, W, et al. Referral and Treatment Patterns of Chronic Hepatitis C. ID Week, 2013, San Francisco, CA. October 2-6, 2013.