Successful hepatitis C treatment reduces HIV disease progression and non-liver-related mortality

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HIV/HCV-co-infected people who achieve a sustained virological response to interferon-based therapy not only reduce their risk of death due to liver disease, but also experience less HIV disease progression and have a lower rate of non-liver-related death, researchers reported at the 17th Conference on Retroviruses and Opportunistic Infections (CROI) last week in San Francisco.

Chronic hepatitis C virus (HCV) infection can lead to complications of advanced liver disease including cirrhosis, liver cancer or liver failure requiring a transplant and liver-related death. HIV-positive people who are co-infected with HCV tend to experience more rapid liver disease progression than those with hepatitis C alone.

Prior studies have shown that interferon-based hepatitis C treatment reduces the likelihood of liver disease progression and liver-related death amongst both HIV-negative and HIV-positive people, especially if they achieve a sustained virological response, or undetectable HCV viral load six months after finishing treatment.

Glossary

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.

disease progression

The worsening of a disease.

AIDS defining condition

Any HIV-related illness included in the list of diagnostic criteria for AIDS, which in the presence of HIV infection result in an AIDS diagnosis. They include opportunistic infections and cancers that are life-threatening in a person with HIV.

hazard

Expresses the risk that, during one very short moment in time, a person will experience an event, given that they have not already done so.

hazard ratio

Comparing one group with another, expresses differences in the risk of something happening. A hazard ratio above 1 means the risk is higher in the group of interest; a hazard ratio below 1 means the risk is lower. Similar to ‘relative risk’.

Juan Berenguer and colleagues performed a study to see if sustained virological response to treatment – considered a 'cure' for hepatitis C – would also affect HIV disease progression and mortality not related to liver disease.

This analysis included 1428 HIV/HCV-co-infected individuals from 20 centres enrolled in the Spanish GESIDA 3603 Study Cohort. About three-quarters were men, the median age was 42 years and 81% had a history of injection drug use.

Just over 80% were on combination antiretroviral therapy, 62% had suppressed HIV viral load and the median current CD4 cell count was a high 528 cells/mm3, but the median nadir (lowest-ever) CD4 count was 216 cells/mm3 and 22% had a prior AIDS diagnosis. A majority (60%) had hard-to-treat HCV genotypes 1 or 4 and about one-third had advanced liver fibrosis.

Participants started treatment with interferon-based therapy between January 2000 and July 2007. Most used the current standard-of-care treatment, pegylated interferon alpha plus ribavirin, but 14% used the older conventional form of interferon.

Overall, 36% of patients achieved a sustained virological response. As expected, the success rate was higher for HCV genotypes 2 or 3 (58%) than for genotypes 1 or 4 (24%). HIV suppression below 50 copies/ml did not appear to affect the likelihood of treatment response.

After a median follow-up duration of about four years, participants who achieved sustained virological response were found to have better outcomes than non-responders (that is, those who never responded, responded only partially or initially responded but relapsed after completing treatment).

Not surprisingly, participants who achieved a sustained response to hepatitis C treatment had lower rates of liver disease complications including decompensation, liver cancer, and transplants.

But the researchers also found that sustained responders were significantly less likely than non-responders to develop new AIDS-defining conditions (0.26 vs 0.94 per 100 person-years).

The overall mortality rate was significantly lower amongst people who successfully responded to hepatitis C treatment than amongst non-responders (0.31 vs 1.71 per 100 person-years).

As expected, sustained responders had a lower rate of death due to liver disease than non-responders (0.10 vs 0.98 per 100 person-years). But again, they also had fewer deaths due to AIDS-defining conditions (0 vs 0.08 per 100 person-years) and mortality attributed to other causes (0.21 vs 0.65 per 100 person-years).

Looking at a combined outcome of progression to a new AIDS-defining condition or non-liver-related death, sustained responders decreased their risk by about two-thirds compared with non-responders (0.47 vs 1.54 per 100 person-years).

A statistical analysis controlling for potentially confounding factors including extent of liver fibrosis, stage of HIV disease and lowest-ever CD4 count showed that individuals who did not achieve a sustained response had a significantly higher risk of developing a new AIDS-defining event (adjusted hazard ratio 3.24, or a more than threefold risk), dying from a non-liver-related cause (adjusted hazard ratio 2.60) or both (adjusted hazard ratio 2.86).

These results indicate that achievement of a sustained virological response to interferon-based hepatitis C treatment in HIV/HCV-co-infected people "reduces not only liver-related complications and mortality, but also HIV progression and mortality not related to liver disease", the researchers concluded.

They suggested that disease progression "may be associated with a poorer immune response (that does not seem to depend on control of HIV) and/or complications of HCV viremia" in individuals who did not achieve a sustained response.

Dr Berenguer briefly showed data from another study presented at the conference, which found that HIV/HCV-coinfected people had elevated levels of biomarkers of endothelial (blood vessel) dysfunction – indicating increased inflammation and atherosclerosis risk – but levels decreased significantly amongst patients who achieved a sustained response to hepatitis C treatment.

At an accompanying press conference, Dr Berenguer was asked whether hepatitis C treatment that does not result in a sustained virological response might also have a beneficial effect.

He replied that this does appear to be the case compared with no treatment. While these data are not yet fully analysed, he said there were "some hints" that co-infected individuals who achieved an end-of-treatment response but later relapsed also appeared to have improved clinical outcomes.

Further information

You can view abstract 167 and abstract 667 on the official conference website.

You can also view a webcast and slides of this session on the official conference website.

References

Berenguer J et al. Sustained virological response to interferon plus ribavirin reduces HIV progression and non-liver-related mortality in patients coinfected with human immunodeficiency virus and hepatitis C virus. Seventeenth Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 167, 2010.

Fernandez de Castro I et al. Hepatitis C infection increases endothelial dysfunction in HIV/HCV co-infected patients. Seventeenth Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 667, 2010.