CROI: Sustained response to hepatitis C treatment lowers liver complications and death in HIV/HCV coinfected people

HIV/HCV coinfected people who achieve sustained response to hepatitis C treatment have a decreased long-term risk of liver-related complications and death, researchers reported Monday at the Fifteenth Conference on Retroviruses and Opportunistic Infections in Boston.

HIV positive people with chronic hepatitis C tend to experience more rapid liver disease progression than individuals infected with only hepatitis C virus (HCV). Amongst hepatitis C monoinfected patients, it has been shown that achievement of sustained virological response (SVR), or continued undetectable HCV viral load six months after completing hepatitis C treatment, reduces liver disease progression. But little is known about the long-term benefits of treatment response in coinfected individuals.

Investigators with the GESIDA 3603 Study Group conducted a long-term analysis of 711 HIV-positive patients at eleven clinical centres in Spain who were treated for chronic hepatitis C between January 2000 and December 2005. Most study participants (72%) were men, the median age was 41 years, 80% had a history of injecting drug use, and 2% were triply infected with hepatitis B.

Just under one-third (63%) had HCV genotypes 1 or 4 and 39% had advanced liver fibrosis (Metavir stage F3-F4) pre-treatment. The participants in general had well controlled HIV. Most (80%) were on combination antiretroviral therapy, the CD4 cell count was 544 cells/mm3, and 52% had HIV viral load under 50 copies/ml; about one-fifth, however, had AIDS.

Most participants had been treated with pegylated interferon (44% with alfa-2a or Pegasys, 38% with alfa-2b or PegIntron) plus ribavirin, though 18% had received conventional (non-pegylated) interferon plus ribavirin.

Overall, 31% of patients achieved sustained virological response to interferon-based therapy, but rates differed by type of HCV: 14% for genotypes 1 and 4 vs. 46% for genotypes 2 and 3. Factors associated with SVR were presence of genotypes 2 or 3, higher nadir (lowest-ever) CD4 cell count, and lower HCV viral load. Both patients who did not respond initially and those who relapsed during or after completion of treatment were classified as non-responders.

Sustained responders and non-responders were followed every six months after completion of treatment, for a median duration of about 20 months, so that the investigators could determine the effect of SVR on outcomes including liver disease, HIV disease progression, liver-related death, and death due to all causes.

After adjusting for various factors associated with an increased risk of death, including AIDS and baseline liver cirrhosis, the investigators found that patients who achieved sustained virological response were significantly less likely than non-responders to develop liver cancer, to progress to decompensated liver disease (abdominal fluid accumulation, upper gastrointestinal bleeding, or hepatic encephalopathy), or to require a liver transplant. None of the sustained responders developed liver cancer or needed a transplant. Looking at all liver-related events together, the non-responders had nearly a nine-fold higher risk compared with sustained responders (hazard ratio 8.92).

Unsurprisingly, patients who achieved a sustained treatment response also had a significantly lower rate of liver-related death. Furthermore, successful anti-hepatitis C treatment was also associated with significantly lower mortality due to all causes. However, there was no difference in new AIDS-defining events between patients who achieved SVR and those who did not.

“Our results suggest that the achievement of a sustained virological response after interferon-ribavirin therapy in HIV/HCV-positive patients reduces liver-related complications and mortality”, the investigators concluded.