CATIE News

18 April 2019 

Canadian study finds hepatitis C virus treatment effective in HIV co-infection

  • A study assessed hepatitis C cure rates for people with complex health challenges
  • Treatment cured most patients, but at lower rates among those who inject drugs
  • Women had a higher cure rate (97%) in this study than men

Hepatitis C virus (HCV) can cause chronic infection of the liver. If left untreated, chronic HCV results in inflammation of the liver and, over time, healthy liver tissue is replaced with scar tissue. Eventually the entire liver will become scarred (a condition called cirrhosis) and serious issues can then arise, including internal bleeding, recurrent abdominal infections, problems with memory and thinking clearly, liver failure and death. There is also an increased risk of liver cancer.

Two decades ago, treatment of HCV infection consisted of a year-long course of weekly injections of interferon-alpha. This therapy caused many side effects and was not highly effective. However, around the year 2013, all-oral regimens (also called direct acting antivirals, DAAs) became available in Canada and other high-income countries. Today, combinations of DAAs are the standard of care and can be taken for shorter periods, depending on the drug used and the degree of liver injury. Commonly used DAAs include the following, all of which are taken once daily:

  • Harvoni – sofosbuvir + ledipasvir
  • Marivet – glecaprevir + pibrentasvir
  • Zepatier – elbasvir and grazoprevir

A note about clinical trials

In pivotal (phase III) clinical trials, these DAAs were highly effective, associated with cure rates of 95% and higher. However, in general, clinical trials run by pharmaceutical companies tend to recruit people who have a condition, in this case chronic HCV infection, but who are otherwise healthy. Such volunteers are not likely to be as ill as some patients seen in community clinics. It is therefore important that once a treatment is licensed doctors in clinics conduct studies with people who were not likely to be enrolled in pivotal clinical trials. Such patients may be more broadly representative of the HCV-infected population.

The Canadian Co-Infection Cohort (CoCo)

Researchers in Canada with CoCo are collecting health-related information from people who have HIV and HCV co-infection. In the latest study from CoCo, researchers assessed the effectiveness of DAAs in almost 300 people who they described as “a population with complex challenges, ongoing substance use, cirrhosis and other co-morbidities.”

Curing HCV

Overall, the researchers found that 92% of participants who initiated HCV treatment were cured of this infection. A high rate of cure (97%) was among women. People who had cirrhosis and/or who injected street drugs multiple times daily were at heightened risk for treatment failure. The researchers suggested potential solutions to reduce the risk of treatment failure in a report published in the journal Open Forum Infectious Diseases.

Study details

CoCo has recruited more than 1,800 people from across Canada who have HIV and HCV co-infection. In the present study, researchers focused on data collected from participants who initiated DAAs between November 2013 and June 2017. Researchers presented results from 286 patients who initiated DAAs and for whom they had complete data.

The average profile of participants upon entry into the present study was as follows:

  • age – 52 years
  • 77% men, 23% women
  • ethno-racial groups: 80% white; 13% Indigenous; 4% black; 3% Asian
  • all participants were taking HIV treatment
  • 89% of participants had a viral load less than 50 copies/mL
  • CD4+ count – 500 cells/mm3
  • past use of interferon-alpha – 31%
  • presence of severe liver injury – 29%
  • 19% had other conditions such as type 2 diabetes, chronic kidney disease or hepatitis B virus infection
  • 20% injected street drugs multiple times daily
  • 30% engaged in what the researchers called “hazardous alcohol consumption”
  • as is typical of the Canadian HCV epidemic, most participants had HCV genotype 1 infection, but a few had genotypes 2, 3 and 4

Result

Overall, 263 out of 286 participants (92%) were cured.

In total, 23 participants experienced what the researchers called treatment failure for the following reasons:

  • virological failure – 11 people
  • relapse – nine people
  • death – three people

Results by different categories

Although, overall, 92% of participants were cured, some subgroups within the study had different cure rates, as follows:

Among people with subtypes of HCV genotype 1, cure rates were as follows:

  • HCV genotype 1b – 97% cured
  • HCV genotype 1a – 92% cured

Among people with other genotypes, cure rates were as follows:

  • HCV genotype 2 – 85% cured
  • HCV genotype 3 – 94% cured
  • HCV genotype 4 – 80% cured

Women were more likely to be cured (97%) than men (90%).

People who had cirrhosis were less likely to be cured (88%) than people without cirrhosis (94%).

People who injected street drugs multiple times each day were less likely to be cured (89%) than people who did not inject street drugs with such frequency (93%).

Bear in mind

In the latest analysis from CoCo, researchers found that the use of DAAs in everyday world co-infected people was “very effective”—a finding that surprised them. They added that DAAs that are likely to become increasingly used in 2019, such as Epclusa and Maviret, will be able to treat all genotypes of HCV. This means that people with genotypes that are not as common as genotype 1 in Canada (genotypes 2 through 6) are more likely to be cured today and in the future.

A note on cirrhosis

Over time, as the liver becomes largely composed of scar tissue, there are problems with blood circulation within this organ. Due to these problems, the concentration of DAAs may be uneven across the liver and some parts of this organ may have less-than-ideal levels of DAAs during a course of treatment. This may increase the risk for virological failure and relapse in some people with cirrhosis.

In the present study from CoCo, researchers found that cirrhosis was associated with a reduced chance of being cured of HCV. A similar finding has been reported in other studies of co-infection. The researchers urged doctors and health systems not to delay the initiation of DAAs for co-infected people.

Frequent daily injecting

As mentioned earlier, the CoCo research team found that that people who engaged in frequent daily injecting of street drugs had a reduced chance of being cured. The researchers noted that injecting cocaine and crystal meth (methamphetamine) likely reduces a person’s ability to take medicines exactly as prescribed and directed. They also said that this population of people who engaged in “high-intensity” injecting “are the same people at high risk for HCV transmission and reinfection, so although [cure] rates are lower, treatment is still effective and should not be withheld. This finding stresses the need for integrative care that includes addiction therapies for drugs other than opioids, adherence support, and harm reduction services to improve treatment outcomes in this priority population for HCV elimination.”

Women

HCV cure rates among women in this study were higher than average. The researchers are unsure why this occurred and suggested that it’s possible that there may be biological explanations for this difference. However, a study of a different design will be needed to better explore and understand why such differences occurred.

For the future

CoCo has enrolled people from different regions in Canada, from urban and rural areas, from hospitals and community clinics. The population in CoCo is representative of the population of people with HIV-HCV co-infection today and so its findings can be generalized across Canada.

There is still much room to improve care and treatment, particularly for people with substance use issues. The latest report from CoCo, with its recommendations for helping people with addictions, points the way forward to such care.

Resources

Hepatitis C drugs approved in Canada for adults

Hepatitis C: An In-Depth Guide

—Sean R. Hosein

REFERENCE:

Rossi C, Young J, Martel-Laferrière V, et al. Direct-acting antiviral treatment failure among hepatitis C and HIV-coinfected patients in clinical care. Open Forum Infectious Diseases. 2019 Feb 13;6(3):ofz055.

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