DAAs achieve excellent outcomes in real-world settings

Hepatitis C virus (HCV) therapy with direct acting antivirals (DAAs) is as effective in real-world settings as it was in clinical trials, according to US research presented to the International Liver Congress in Barcelona last week. Investigators from the Department of Veteran Affairs (VA) analysed outcomes in over 9000 patients treated with DAA combinations. Outcomes were excellent, with two combinations achieving cure rates of 93%, similar to those seen in randomised studies with strict eligibility criteria and close follow-up.

The development of DAAs has revolutionised HCV treatment and care. The aim of treatment is an undetectable viral load twelve weeks after the completion of therapy, usually called a sustained virological response (SVR12). Several DAA regimens have performed well in clinical trials, achieving SVR12 rates of 90% or more. However, there are limited data on the effectiveness of DAAs in routine care settings and it is therefore unclear if the impressive results observed in clinical trials can be replicated in the real world.

Researchers from the VA therefore analysed the records of 9,604 people with hepatitis C who completed therapy with a DAA combination and were followed until twelve weeks after the completion of treatment.

Glossary

sustained virological response (SVR)

The continued, long-term suppression of a virus as a result of treatment. In hepatitis C, refers to undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 12 or 24 weeks after ending treatment and is considered to be a cure (SVR12 or SVR24).

antiviral

A drug that acts against a virus or viruses.

cure

To eliminate a disease or a condition in an individual, or to fully restore health. A cure for HIV infection is one of the ultimate long-term goals of research today. It refers to a strategy or strategies that would eliminate HIV from a person’s body, or permanently control the virus and render it unable to cause disease. A ‘sterilising’ cure would completely eliminate the virus. A ‘functional’ cure would suppress HIV viral load, keeping it below the level of detection without the use of ART. The virus would not be eliminated from the body but would be effectively controlled and prevented from causing any illness. 

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

The patients received one of three regimens:

  • simeprevir/sofosbuvir (3,064)
  • ledipasvir/sofosbuvir (5,524)
  • ombitasvir/paritaprevir/ritonavir/dasabuvir (3D) (1,012)

The overwhelming majority (96.3%) of patients were male, 65.1% were aged between 60 and 65 years and 75.4% had HCV genotype 1.

Patients with more advanced liver disease at baseline were more likely to have received therapy with simeprevir/sofosbuvir, the first of the study regimens to come to market.

All three combinations achieved impressive SVR12 rates.

  • simeprevir/sofosbuvir = 87.3%
  • ledipasvir/sofosbuvir = 93.2%
  • 3D = 93.4%

After controlling for baseline characteristics, people taking ledipasvir/sofosbuvir and people taking the 3D combination were significantly more likely to achieve SVR12 than people taking simeprevir/sofosbuvir. The severity of baseline liver disease affected treatment outcomes, with more severe disease associated with lower chances of achieving SVR12. Non-genotype 1 infection was also associated with reduced odds of sustained viral suppression.

Encouragingly, co-infection with HIV did not affect treatment outcomes.

The investigators conclude that use of DAA combinations in routine settings have been found “to fulfill their promise of greater than 90%, as first documented in randomized clinical trials.”

References

McCombs J et al. Analysis of the real-world effectiveness of direct acting antiviral treatments for hepatitis C in a large population. International Liver Congress, Barcelona, 2016.