Routine clinical use of DAAs highly effective and safe in people with HIV/HCV in Europe

“Real life” data from across Europe shows that direct-acting antivirals (DAAs) cure hepatitis C in the vast majority of people with HIV and hepatitis C virus (HCV) co-infection who receive treatment, according to research presented at the 2018 International Liver Congress in Paris. Only a small number of people stopped treatment because of side-effects, most of which were related to ribavirin. A cure was observed in 92.5% of people with sustained virological response (SVR) data. Outcomes were similar across Europe.

“In a diverse population of HIV/HCV co-infected patients from all regions in Europe, DAA therapy resulted in an overall SVR rate of 92.5% which is similar to what has been shown for national cohorts in Western Europe,” write the investigators. “There were no significant differences in response across regions, although with limited power in Central East and Eastern Europe, and further follow-up is warranted to confirm these findings.”

Results from clinical trials show that DAAs are highly effective and safe in people with HIV/HCV co-infection. However, European data on outcomes when DAAs are used in routine clinical care are largely lacking.

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).

toxicity

Side-effects.

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. 

prospective study

A type of longitudinal study in which people join the study and information is then collected on them for several weeks, months or years. 

cirrhosis

Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 

Investigators from the EuroSIDA collaboration designed a prospective study involving 632 adults with co-infection who started DAA therapy between June 2014 and March 2017. Information was collected on treatment response, discontinuations due to toxicity and side-effects.

The study participants had a median age of 51 years, 79% were men, 58% had a history of injecting drug use and a third had liver cirrhosis. HIV infection was well controlled: 99% had an HIV viral load below 500 copies/ml and the median CD4 cell count was 600 cells/mm3.

The most commonly used HCV regimens were sofosbuvir and ledipasvir with or without ribavirin (46%) and sofosbuvir with daclatasvir with or without ribavirin (20%).

SVR data were available for 468 people – approximately two-thirds of the cohort – and 93% of these individuals attained SVR.

SVR status was unknown in 164 people, but 50% of these individuals had an undetectable HCV viral load at the end of therapy, the other 50% of individuals having an unknown treatment response. People with unknown SVR status were slightly more likely to be located in Central East and Eastern Europe (p = 0.059).

The only factors associated with increased chances of SVR were white vs non-white race, less advanced fibrosis (stage 0-1 vs stage 2-4) and longer duration of therapy.

At least one drug was stopped early by 5% of people. Reasons included toxicity (n = 11), viral failure (n = 11), physician choice (n = 3), drug stock-out (n = 1), substance abuse (n = 1) and other/unknown (n = 14).

The median duration of therapy was nine weeks for people who interrupted therapy because of toxicity compared to 12 weeks for people who did not experience any toxicity-related interruptions.

Nine out of the eleven toxicity-related discontinuations were related to well-known ribavirin-related side-effects.

“A quarter of all persons who completed treatment did not have a follow-up HCV-RNA to determine SVR12. This could reflect other follow-up schedules than what is seen in clinical trials; treatment outside the HIV clinic, loss to follow-up or data not reported and requires further data to clarify,” conclude the researchers. “Only 5% stopped one or more HCV drugs earlier than scheduled, and a third of these were due to toxicity mostly related to well-known adverse effects of ribavirin. We saw no new safety signals for DAAs.”

References

Peters L et a. Efficacy and safety of IFN-free DAA HCV therapy in HIV/HCV co-infected persons: results from a pan-European study. The International Liver Congress, Paris, abstract THU-309, 2018. Journal of Hepatology 68: S268, 2018.