A quarter of HIV/HCV-co-infected people in EuroSIDA have received HCV therapy

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A quarter of HIV-positive people in the EuroSIDA cohort with chronic hepatitis C virus (HCV) co-infection have received HCV therapy, a study published in HIV Medicine shows. The proportion of people treated increased significantly between 1998 and 2007 but then fell, possibly because patients and doctors were awaiting for the arrival of new direct-acting anti-HCV drugs.

More worryingly, the study showed that only 36% of treated people had significant fibrosis and that a fifth of untreated people had liver damage serious enough to warrant therapy.

“There remain patients, including some with significant fibrosis, who have not been exposed to anti-HCV treatment,” comment the authors.

Glossary

fibrosis

Thickening and scarring of connective tissue. Often refers to fibrosis of the liver, which can be caused by an inflammatory reaction to long-term hepatitis infection. See also ‘cirrhosis’, which is more severe scarring.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

naive

In HIV, an individual who is ‘treatment naive’ has never taken anti-HIV treatment before.

ribonucleic acid (RNA)

The chemical structure that carries genetic instructions for protein synthesis. Although DNA is the primary genetic material of cells, RNA is the genetic material for some viruses like HIV.

 

treatment-naive

A person who has never taken treatment for a condition.

A significant proportion of HIV-positive people are co-infected with HCV. Liver disease caused by this co-infection is now an important cause of death in these people.

HCV can be treated and cured. Guidelines recommend that HIV-positive people with significant liver fibrosis (stage F2 or above) should receive HCV therapy. People with well-controlled HIV infection (a CD4 cell count above 350 cells/mm3) are also a priority group for treatment.

Despite these recommendations, little is known about the uptake of HCV therapy among co-infected people.

Investigators from the EuroSIDA cohort study therefore analysed data collected between 1998 and 2010 to see if rates of treatment were increasing, the factors associated with starting therapy, and if patients prioritised by guidelines were receiving treatment.

The EuroSIDA cohort comprises approximately 18,300 HIV-positive people in Europe, Israel and Argentina. A total of 4224 of these people have antibodies to HCV. HCV viral load measurements were available for 2663 of these participants and 2008 (76%) were found to be HCV RNA positive. Some 1984 of these people were HCV-treatment naive at baseline and eligible for inclusion in the study.

These 1984 people contributed 18,303 person-years of follow-up. During this time, 501 (25%) started HCV treatment, a rate of 2.74 per 100 person-years of follow-up.

The overall incidence of treatment increased over time from just 0.33 per 100 person-years of follow-up in 1998 to 5.93 per 100 person-years of follow-up in 2007.

Between 1998 and 2007, the incidence of treatment uptake increased by a significant 26% each year (p < 0.0001).

“The increasing uptake of anti-HCV therapy probably reflects the introduction of peg-IFN [pegylated interferon], with cure rates of approximately 70% for HCV genotype 2 or 3 and 35% for genotype 1 or 4,” suggest the authors.

However, after 2007, treatment uptake fell. In 2009 it was 3.74 per 100 person-years of follow-up. “The trend of decreasing treatment uptake seen after a peak in 2007 is explained by different patient characteristics and possibly treatment saturation of the easy-to-treat patients,” write the authors. An alternative explanation offered by the authors is that patients and doctors were “choosing to wait for the first generation of directly acting agents”.

People in Southern Europe were especially likely to start treatment, as were gay men. The investigators believe that the higher treatment rates in Southern Europe could be due to greater physician experience. Many of the infections among gay men have been detected during the acute phase, and therapy has an especially high success rate when administered at this time.

Several patient characteristics were also associated with the receipt of therapy. These included a suppressed HIV viral load (p = 0.012), a higher HCV viral load (p = 0.049) and elevations in ALT levels (p < 0.0001).

Information on liver fibrosis was available for 800 participants (40%). People with significant fibrosis were 60% more likely (p < 0.0065) to have received therapy compared to people with less severe liver damage.

However, only 36% of individuals of treated patients had F2 fibrosis or above, and 22% of patients with severe fibrosis were still waiting to start therapy.

“We have reported an increase in the incidence of treatment for HCV infection in EuroSIDA, with those selected for treatment mostly aligned with current guidelines,” conclude the authors. However, they express concern that a significant proportion of people with serious liver fibrosis remain untreated. “Future studies of the reasons for this are warranted.”

References

Grint D et al. Temporal changes and regional differences in treatment uptake of hepatitis C therapy in EuroSIDA. HIV Medicine, doi: 10.1111/hiv.12068, 2013.