'Sensational' HCV response rates in HIV coinfection trial

Researchers in the C-EDGE study found that a combination of a protease inhibitor and an NS5A inhibitor led to a sustained virologic response in patients infected with both HIV and hepatitis C virus (HCV).

Researchers in the C-EDGE study found that a combination of a protease inhibitor and an NS5A inhibitor led to a sustained virologic response in patients infected with both HIV and hepatitis C virus (HCV). Jurgen Rockstroh, MD, of the University of Bonn in Germany, reported that the sustained virologic response was 96.3% overall after stopping treatment for 12 weeks. The response rate for the 35 patients with cirrhosis at baseline was 100%. Of the study's 218 patients, two experienced a relapse after stopping therapy, but both had been reinfected with HCV. The Phase III study included patients infected with HCV genotypes 1, 4, or 6, and HIV. All patients received grazoprevir 100 mg and elbasvir 50 mg, which were coformulated by Merck into one tablet that was taken once daily for 12 weeks. No patients experienced any serious drug-related adverse events during the study. The results were presented at the International AIDS Society Conference in Vancouver.

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Rural docs want looser rules for Hepatitis C treatment

INDIANAPOLIS – The only doctor at the center of an HIV outbreak in rural Indiana cannot prescribe the latest treatments for patients also infected with the deadly Hepatitis C virus.

Dr. William Cooke, a family practitioner in Scott County, is treating dozens of people with HIV, the AIDS-causing virus that exploded in numbers among intravenous drug users earlier this year.

But state Medicaid rules forbid him from prescribing new treatments to those same patients with Hepatitis C, the blood-borne disease that causes inflammation in the liver and now claims more lives than HIV in the United States.

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Liver transplants in HIV/HCV co-infection: study underlines importance of hepatitis C treatment

People with HIV and hepatitis C co-infection were significantly more likely to experience organ rejection than people with hepatitis C alone or HIV alone after undergoing a liver transplant, according to a review of 11 years' experience of liver transplantation in people with HIV and with hepatitis C virus (HCV) in the United States, published in advance online in the journal Clinical Infectious Diseases.

The study investigators say that their findings underline the importance of treating hepatitis C either before or immediately after liver transplantation in order to improve outcomes, rather than assuming that people with co-infection will have poorer outcomes based on historical data.

Liver transplantation remains a relatively rare procedure among people living with HIV, due in part to concerns about poorer survival and higher rates of organ rejection in people with HIV. Although a study carried out by the United States National Institutes of Health (NIH) showed a somewhat lower rate of survival three years after transplantation and a higher rate of organ rejection in people with HIV and hepatitis C co-infection compared to people with hepatitis C alone (mono-infection), the majority of transplants in each group was successful. The success of transplantation in people with HIV who are not do not have hepatitis C co-infection has been unclear. Furthermore, data are lacking outside the clinical trial setting regarding the outcomes of transplants in people with co-infection, particularly at transplant centres which did not take part in the NIH trial.

Reference

Sawinski D et al. Beyond the NIH Multicenter HIV Transplant Trial experience: outcomes of HIV+ liver transplant recipients compared to HCV+ or HIV+/HCV+ co-infected recipients in the United States. Clin Infect Dis, advance online publication, 16 June 2015.

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Snapshots, by Alan Franciscus, Editor-in-Chief

Article: Prevalence and risk factors for patient-reported joint pain among patients with HIV/Hepatitis C coinfection, Hepatitis C monoinfection, and HIV monoinfection—A Ogdie et al.
   Source:  BMC Musculoskeletal Disorders 2015, 16:93  doi:10.1186/s12891-015-0552-z

A common symptom that people with hepatitis C report is pain—liver pain, muscle and joint pain, fibromyalgia, headaches and the list goes on and on.  The aim of the current study was to determine the prevalence of patient reported joint pain among 3 groups (a total of 202 patients, mostly males): HCV mono-infection (93 patients); HIV-mono-infection (30 patients); and HIV/HCV co-infection (79 patients).  The ages and genders were similar across all three groups.  More than half were Black. 

The Multi-Dimensional Health Assessment Questionnaire was used to determine joint pain and any related symptoms. The patients were also interviewed and their charts were reviewed. 

The Bottom Line:  Joint pain was more commonly reported in HCV-monoinfected patients than in HIV/HCV-coinfected patients—71% vs. 56.  Joint paint was also more commonly reported in HCV mono-infected patients than in HIV-monoinfected patients—71% vs 50%.

The study found that a previous diagnosis of arthritis and current smoking were risk factors for joint pain among people who are infected with hepatitis C. 

Editorial Comment:  This is another reason why everyone with hepatitis C should be treated.  There are so many symptoms and conditions caused by hepatitis C.   

For more information see this month’s HealthWise.

Article: Liver-related death among HIV/hepatitis C virus-co-infected individuals: implications for the era of directly acting antivirals—D Grint et al. 
   Source: AIDS. 2015 Apr 13. [Epub ahead of print]

The new interferon-free therapies provide similar cure rates in people who are co-infected with HIV and hepatitis C as in people who are mono-infected with hepatitis C.  However, access is being restricted due the higher costs of the newer medications.  

In general, people who are co-infected with HIV and hepatitis C have a faster rate of HCV disease progression than someone with hepatitis C mono-infection.  Even so, treatment is being restricted to those with the greatest risk of liver-related death.  The current study sought to provide a degree of guidance on who should be prioritized for receiving the new direct acting antiviral medications (DAAs) or HCV inhibitor combination medications.  The study looked at the liver-related deaths of the people who were co-infected with HIV and hepatitis C.

In the current study 3,941 HCV antibody positive patients who were part of a European study (EuroSIDA) and who were followed-up after 1 January 2000 were included. 

Liver-related deaths accounted for 145 of 670 (21.6%) deaths in the study population. Liver-related death rates peaked in those aged 35-45 years, and occurred almost exclusively in those with at least F2 fibrosis at baseline.  Note: The Metavir scale is F0, no activity, F1 for inflammation, F2 for light scarring, F3 for moderate-severe scarring and F4 for cirrhosis. 

The Bottom Line: The authors reported that the 5- year probability of liver related death (LRD) was low for those with F0-F1, but substantial for those F2, F3 and F4. 

The authors also noted that “treatment with DAAs should be prioritized for those with at least a F2 fibrosis.  Early initiation of cART with the aim of avoiding low CD4 cell counts should be considered essential to decrease the risk of LRD and the need for HCV treatment.” 

Editorial Comment:  I wonder how many people coinfected with HIV/HCV are F0-F1, how quickly people progress from one stage to another, how often do you need to monitor people in stage F0/F1, how much does it cost to monitor, and would it be cheaper in the long run to treat everyone?  

Article: Hepatitis A and B among young persons who inject drugs—Vaccination, past, and present infection. MG Collier et al.
  Source:  Vaccine. 2015 Apr 15. pii: S0264-410X(15)00472-7. doi: 10.1016/j.vaccine.2015.04.019. [Epub ahead of print]

It is recommended that people who inject drugs (PWID) should be vaccinated against hepatitis A (HAV) and hepatitis B (HBV). There is some evidence that some young individuals who were vaccinated as children may have lost their immunity.  The current study sought to understand the current HAV and HBV immunity status among 519 persons who inject drugs.   The study group included 18 to 40 year olds who lived in San Diego—49% were non-Hispanic white, 7% were non-Hispanic Blank, 27% were White Hispanic, 4% were born outside of the U.S. 

The Bottom Line:  After being tested it was found that 47% were susceptible to HBV infection and 63% were susceptible to hepatitis A infection.  Additionally, 26% tested positive for HCV antibodies.  The authors reported that even though the participants believed that they had been vaccinated, many had not.  The authors commented that "Programs serving this population should vaccinate PWIDs against HAV and HBV and not rely on self-report of vaccination."

 
Editorial Comment:  This recommendation makes perfect sense. People forget about what vaccines they received as children or if they were vaccinated at all.  If you have hepatitis C it is even more important to be protected.  Becoming co-infected with another hepatitis virus such as HAV or HBV can lead to serious health consequences, even death.   The HAV vaccine can be given without serologic testing since it will do no actual harm.   It is important, however, to give the HBV serologic test to make sure that people are not already infected with the hepatitis B virus before giving the HBV vaccine.  The HBV vaccine doesn’t provide any benefit to people who have acute or chronic HBV and might just might give people a false sense of security and prevent much needed follow-up medical care.

http://hcvadvocate.org/news/newsLetter/2015/advocate0615.html#3

Almost three quarters of HIV/HCV group may have DDA-ARV interactions

Among 125 HIV/HCV-coinfected people taking antiretrovirals in a Denver group, 70% could have moderate or severe interactions with one of four common direct-acting antiviral (DAA) regimens for HCV [1]. Researchers calculated that 20% of patients who needed to switch antiretrovirals because of certain DAA interactions could not switch because of antiretroviral resistance.
 
This retrospective study involved 125 HIV/HCV-coinfected adults with antiretrovirals prescribed within the last year. All participants were in care at an academic medical center in Denver. Researchers assessed potential interactions between each person's antiretroviral regimen and four possible DAA combinations: simeprevir and sofosbuvir (SIM/SOF), sofosbuvir and ledipasvir (SOF/LDV), sofosbuvir and daclatasvir (SOF/DCV), and ritonavir-boosted paritaprevir plus dasabuvir and ombitasvir (3D). The analysis did not explore potential interactions between non-HIV drugs and DAAs.

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Harvoni added benefit for patients with HCV/HIV coinfection

In a manufacturer dossier assessment conducted by the Institute for Quality and Efficiency in Health Care in Germany, Harvoni was deemed to have an added benefit for patients with hepatitis C genotype 1a virus infection and HIV without cirrhosis, according to a press release.

The dossier assessment is a procedural part of the Reform of the Market for Medicinal Products Act, overseen by the Federal Joint Committee (G-BA). The G-BA conducts a commenting procedure once the dossier assessment is complete and then determines the extent of the added benefit determined by the Institute for Quality and Efficacy in Health Care (IQWiG).

The assessment was based on additional data from five clinical studies submitted by Gilead Sciences. The information led the IQWiG to conclude that SVR achieved by patients without HIV coinfection was “transferable” to patients with HIV coinfection without cirrhosis. However, the extent of the added benefit in this population of patients is “non-quantifiable” due to the fact it is unclear in how many patients with undetectable viral load prevention of late complications and liver cancer can be achieved, according to the release.

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Few Children Vertically Co-Infected With HIV and HCV Are Treated for HCV and the Response Is Low: Presented at ESPID

LEIPZIG, Germany -- May 15, 2015 -- Approximately 20% of children vertically infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) had already developed liver fibrosis by the end of adolescence, according to findings presented during a Short Oral Presentation Session on May 14th at the 33rd Annual Meeting of the European Society of Paediatric Infectious Diseases (ESPID).

“Rates of sustained viral response were very low in this small cohort, arousing the need of new therapeutic approaches for this population that may benefit from new drugs for HCV treatment,” said Talia Sainz-Costa, MD, Paediatrics, La Paz University Hospital, IdiPAZ Health Research Institute, Madrid, Spain, who noted the paucity of data regarding the natural history of children with vertical HIV/HCV co-infection and their response to anti-HCV treatment.

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Grazoprevir/Elbasvir, Merck’s Investigational Chronic Hepatitis C Therapy, Granted FDA Breakthrough Therapy Designations; New Phase 2 and 3 Data in Multiple HCV Patient Types to be Presented at The International Liver Congress™ 2015

Congress Highlights Include Results from Trials in a Wide Range of HCV Patients -- Patients with Chronic Kidney Disease, HIV Co-infection, Cirrhosis, and Prior Treatment Failures

Company Remains on Track for NDA Filing with the U.S. FDA During First Half of 2015 

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced that grazoprevir/elbasvir, an investigational single tablet regimen for the treatment of chronic hepatitis C virus (HCV) infection, has received two new Breakthrough Therapy designations from the U.S. Food and Drug Administration (FDA) for the treatment of patients with chronic HCV genotype 4 (GT4) infection, and for the treatment of chronic HCV genotype 1 (GT1) infection in patients with end stage renal disease on hemodialysis. Additionally, the company announced presentations from the broad grazoprevir/elbasvir development program at the upcoming International Liver Congress™. A total of 14 abstracts from studies evaluating grazoprevir/elbasvir are scheduled to be presented, including three from the company’s ongoing Phase 3 pivotal C-EDGE program, one from the pivotal Phase 2b/3 C-SURFER study, and seven from ongoing or completed Phase 2 studies. The range of data to be presented underscores the company’s ongoing commitment to developing an all-oral regimen with wide application across diverse patient populations. The International Liver Congress™ 2015 – the 50^th annual congress of the European Association for the Study of the Liver – is scheduled to take place at the Reed Messe Convention Center, Vienna, Austria, from April 22 – 26, 2015.

“HCV remains a global public health epidemic. At Merck, we are focused on the development of an efficacious, well-tolerated, once-daily therapy that can be used to treat multiple genotypes and a diverse population of chronic HCV patients,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “Our clinical program is among the largest and most comprehensive, with studies dedicated to patient populations where significant unmet medical need still exists, such as prior treatment failures, as well as those living with co-morbid conditions, including HIV infection, chronic kidney disease and individuals on opiate substitution therapy.”

In October 2013, the FDA granted Breakthrough Therapy designation for grazoprevir/elbasvir for the treatment of patients with chronic HCV genotype 1 (GT1). In January 2015, the FDA notified Merck of its intention to rescind that Breakthrough Therapy designation. The FDA has now granted two new Breakthrough Therapy designations for grazoprevir/elbasvir; the designations are now for the treatment of patients infected with chronic HCV GT1 with end stage renal disease on hemodialysis, and patients infected with chronic HCV genotype 4 (GT4). Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

At The International Liver Congress 2015™, key data presentations will include:

• Primary results from the C-EDGE program, Phase 3 clinical trials evaluating grazoprevir/elbasvir (with and without ribavirin) across multiple HCV genotypes (1, 4 and 6) and diverse patient populations, including those difficult to treat, over a 12-week treatment duration
  • C-EDGE TN in treatment-naïve patients; Oral presentation, General Session 2 & Award 1, Abstract #G07, Friday, April 24, 8:30 a.m. – 8:45 a.m. CEST
  • C-EDGE CO-INFXN in patients with HCV/HIV co-infection; E-poster #P0887, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
  • C-EDGE TE in treatment-experienced (prior peg-interferon/ribavirin treatment failures); E-poster #P0886, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST

• First results from C-SURFER, a Phase 2b/3 clinical trial evaluating grazoprevir/elbasvir (without ribavirin) in treatment-naïve and treatment-experienced patients with HCV genotype 1 infection and advanced chronic kidney disease
  • Late-breaking E-poster #LP02, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
• Results from C-SALVAGE, a Phase 2 clinical trial evaluating grazoprevir/elbasvir (with and without ribavirin) for chronic HCV in genotype 1 infection after failure of direct-acting antiviral (DAA) therapy, including boceprevir, telaprevir, or simeprevir
  • Oral presentation, Viral Hepatitis C Therapy session, Abstract #O001, Thursday, April 23, 4:00 p.m. – 4:15 p.m. CEST
• Results from C-SWIFT, a Phase 2 clinical trial evaluating shorter treatment durations (4, 6, 8 and 12 weeks) of grazoprevir/elbasvir plus sofosbuvir in treatment-naïve, treatment-experienced/prior treatment failure/null-response, cirrhotic and non-cirrhotic patients with genotype 1 or 3 infection
  • Oral presentation, Viral Hepatitis C Therapy session, Abstract #O006, Thursday, April 23, 5:15 p.m. – 5:30 p.m. CEST
• Phase 2 efficacy and safety results from the C-SALT clinical trial, evaluating grazoprevir/elbasvir in genotype 1 infected patients with Child-Pugh class B cirrhosis
  • Oral presentation, Viral Hepatitis C Therapy session, Abstract #O008, Thursday, April 23, 5:45 p.m. – 6:00 p.m. CEST
• Results from C-WORTHy, a Phase 2 clinical trial evaluating treatment with grazoprevir/elbasvir (with or without ribavirin) in genotype 1 and 3 infection, and in a variety of patient sub-populations including treatment-naïve, treatment-experienced, cirrhotic, non-cirrhotic, and HIV/HCV co-infected
  • C-WORTHy Part C in treatment-naïve, non-cirrhotic patients with genotype 1b infection; E-poster #P0769, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
  • C-WORTHy Part D in treatment-naïve patients with genotype 3 infection treated with ribavirin; E-poster #P0776, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
  • C-WORTHy resistance analysis of virologic failures in hepatitis C genotype 1 infected patients; E-poster #P0891, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
• Results from C-SCAPE, a Phase 2 trial evaluating the efficacy and safety of 12 weeks of grazoprevir/elbasvir (with or without ribavirin) in patients with genotype 2, 4, 5 or 6 infection
  • E-poster #P0771, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
• Results from a Phase 1 study to evaluate the interaction of novel nucleotide inhibitor MK-3682 (formerly IDX21437), with grazoprevir and NS5A inhibitor MK-8408 in healthy subjects
  • E-poster #P0824, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST

About Grazoprevir/Elbasvir
Grazoprevir/elbasvir is an investigational, once-daily single tablet regimen consisting of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A replication complex inhibitor). As part of Merck’s broad clinical trials program, grazoprevir/elbasvir is being studied in multiple HCV genotypes and in patients with difficult-to-treat conditions such as HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, cirrhosis and those on opiate substitution therapy.

Read complete press release here...

HIV rebound linked to liver fibrosis progression in HIV/HCV coinfected

HIV-positive people with hepatitis C virus (HCV) experienced progression to liver fibrosis if their HIV viral load rebounded above 1000 copies/mL or remained detectable on 2 consecutive tests, researchers reported in the January edition of HIV Medicine. Smaller transient HIV "blips," however, were not associated with worsening fibrosis. Optimized antiretroviral therapy, the study authors suggested, may protect the liver.

HIV/HCV coinfected people are known to experience more rapid liver fibrosis progression than people with hepatitis C alone, though the reason for this is not fully understood. SMART and other studies have shown that interruption of antiretroviral therapy (ART) and lack of HIV viral suppression are associated with liver, heart, and kidney disease, but it is not known what level of viremia affects liver fibrosis progression.

Curtis Cooper and fellow investigators with the Canadian Co-infection Cohort Study looked at the relationship between HIV viral load and fibrosis progression in 288 HIV/HCV coinfected people in the cohort. A majority (74%) were men, the mean age was 45 years, and the median CD4 T-cell count was 440 cells/mm³. Most (81%) reported a history of injection drug use and half currently drank alcohol.

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Native AIDS Survivor, Activist Runs Marathon: ‘We CAN Run Marathons too’

On January 18, 2015, I completed my first full marathon in Phoenix. It wasn’t easy because statistics told me Natives have the shortest life span after HIV infection.

Back in 2002 when I was diagnosed with HIV and Hepatitis C in Phoenix, my health was at a border between HIV and AIDS. I was immediately taken to a Native AIDS support group. To this day, I am the only one from that group who is still alive.

Born and raised on the San Carlos Apache Reservation in Arizona, I never thought a tribal would get AIDS. Education was extremely limited about the virus. Rumors were rampant when the virus was discovered, and I remember looking for red or purple spots on my body thinking it was Kaposi’s Sarcoma, a disease AIDS patients got in the early days.

Read more at http://indiancountrytodaymedianetwork.com/2015/01/23/native-aids-survivor-activist-runs-marathon-we-can-run-marathons-too-158837