Assess HIV/HCV patients' response to interferon
July 1, 2008 5 minutes read
Assess HIV/HCV patients' response to interferon
Non-responders gain nothing from treatment
HIV/HCV coinfected patients who do not respond early on to interferon treatment will gain nothing from continued treatment, according to a study that looked at whether interferon treatment could slow liver disease progression among patients who were nonresponders to early interferon plus ribavirin treatment.1
Studies have shown that about half of the people who are infected with hepatitis C will respond to treatment with an interferon-based regimen. And a significant portion of these people will be cured of the disease, says Kenneth E. Sherman, MD, PhD, the Gould professor of medicine and director of the Division of Digestive Diseases at the University of Cincinnati College of Medicine in Cincinnati, OH. Sherman was the principal investigator of the HCV maintenance treatment study.
"Hepatitis C treatment has evolved over the years, but it still remains dependent on the use of interferon and, in the last decade, ribavirin," Sherman says. "Those medications are difficult to tolerate even in mono-infected patients, and the lack of experience and training in the infectious disease community with these agents has made their volume of use minimal among HCV/HIV coinfected patients."
The question Sherman's study sought to answer was whether continued interferon treatment provided any benefits in the maintenance of HIV/HCV patients who were not early responders to the treatment.
The study examined outcomes of 329 co-infected HIV/HCV patients who were treated with pegylated interferon plus weight-based ribavirin for 12 to 18 weeks. About 55% of the patients were determined to have early virologic response to the treatment, based on virologic levels at week 12.
"We learned from pivotal trials that at 12 weeks we could identify who was going to be a nonresponder with nearly 100% certainty," Sherman says. "Early viral response (EVR) is defined as a undetectable hepatitis C virus at 12 weeks or a drop of two logs in HCV from baseline."
Patients who don't achieve one of those two definitions have no chance of cure of their HCV disease using standard treatment regimens, he adds.
44% of the study's participants did not achieve early viral response. These subjects, who did not respond at 12 weeks, were randomly placed in a group that continued to receive the interferon treatment versus an observation arm for 72 weeks, at which time another liver biopsy would be performed. However, the study was stopped early by a data safety monitoring board because of futility in exposing the intervention arm to the continued treatment.1
"There was no fibrotic progression in the observation arm," Sherman says. "In addition, there was a trend — not statistically significant — that showed a slight worsening of fibrosis in the treatment arm, so the safety monitoring board recommended that the maintenance arm be terminated and no more patients undergo liver biopsy."
On the positive side, the study had a higher than anticipated number of HIV/HCV patients who were early responders to the HCV treatment, Sherman notes.
"The only difference between our study and similar investigations was that we used weight-based ribavirin dosing," Sherman says. "Based on historical controls, weight-based ribavirin appears to be more effective."
The study's other key finding was that response rates to HCV treatment varied by patients' race. White, non-Hispanic patients had the best response of 64.8%, while Hispanics had a 56% response rate, and black, non-Hispanic patients had a 42.3% response rate, Sherman says.
"That's a significant difference in racial response," Sherman says. "That difference has been noted in mono-infected patients, but not previously described among co-infected patients, and that was one of the big findings."
In Sherman's research and clinical work, he's seen problems in the treatment of HIV/HCV patients because of the specialization of care that leaves many HIV clinicians with too limited knowledge about HCV.
"There tends to be a minimization of understanding of the role of hepatitis C and HIV coinfection," Sherman says.
So treatment of co-infected HIV/HCV patients is somewhat disjointed.
Add to this the reality that patients with HIV/HCV coinfection have a lower response rate to HCV treatment than do mono-infected HCV patients, and those with the HIV/HCV coinfection have a rate of liver fibrosis that is faster than in mono-infected patients, Sherman says.
"Put those two factors together — less people cured and faster disease progression, and you have a recipe for disaster in terms of developing long-term liver disease," he says.
This is why HCV infection is a leading cause of death among HIV patients, Sherman says.
"It's an important disease and there are far better outcomes in those who are appropriately treated and subsequently cured," Sherman says.
"I think there needs to be more focused training in the management of liver disease among HIV caregivers, and I've been a big proponent of that for a number of years," Sherman says.
There are a number of ways HIV clinicians could reduce morbidity and mortality from HIV/HCV coinfection, and the first step is to screen all HIV patients for HCV, Sherman says.
"Treatment decisions are often being made in a vacuum in terms of HIV management that does not include identification of hepatitis C," he says. "There's a certain complacency in the HIV community regarding abnormal liver tests."
Treating opportunistic infections (OIs) became the top priority, and so liver problems were considered less relevant, he notes.
"The optimal evaluation includes an evaluation of liver histology with a liver biopsy, and HIV clinicians don't do liver biopsies in general," Sherman says. "And in their training they have little experience with interpretation of biopsy results."
Also, HIV clinicians should monitor patients who fail HCV treatment for advanced liver disease, he says.
"They need to consider transplantation in those patients," Sherman says. "The lack of understanding of liver disease is so high among many HIV practitioners that frequently we are called in very, very late in the disease — beyond the time when patients might be suitable candidates for transplantation."
Since there now are about 20 centers in the United States that will do transplants in HIV patients, this failure to refer patients for transplantation has dire consequences, he adds.
Reference
- Sherman K, Andersen J, Butt A, et al. Sustained long-term antiviral maintenance with pegylated interferon in HCV/HIV-co-infected patients: early viral response and effect on fibrosis in treated and control subjects. Abstract 59. Presented at the 15th Conference on Retroviruses and Opportunistic Infections. Feb. 3-6, 2008, Boston, MA.
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