HIV/HCV Coinfected Patients Who Respond to Interferon-based Therapy Experience More Side Effects than Non-responders

		SUMMARY: Among HIV positive patients treated with pegylated interferon plus ribavirin for chronic hepatitis C, those who experience side effects such as depression and anemia, as well as reduced CD4 cell count, were more like to achieve virological response, researchers from the U.S. National Institutes of Health reported in the January 23, 2010 advance online Journal of Acquired Immune Deficiency Syndromes.

By Liz Highleyman

People with HIV/HCV coinfection tend to respond less well to interferon-based therapy for hepatitis C. Rapid virological response at week 4 is a reliable indicator of sustained response, but there may also be other predictors.

Anu Osinusi and colleagues aimed to determine whether interferon-related adverse side effects were associated with HCV virological response in coinfected patients.
The investigators conducted 2 prospective, open-label trials in which HIV/HCV coinfected participants were treated with pegylated interferon alpha-2a (Pegasys) or pegylated interferon alpha-2b (PegIntron) plus ribavirin for 48 weeks.

The researchers analyzed treatment safety and efficacy by assessing HCV RNA levels, laboratory data, psychiatric side effects (e.g., depression, anxiety), and ophthalmologic (eye) evaluations at baseline and monthly through week 72. Responders were defined as patients who experienced HCV RNA decline of at least 2 logs from baseline, while non-responders did not.

Results

	Of the 27 patients (50%) who experienced psychiatric side effects, 26 were virological responders.
	In contrast, only 1 of the 14 non-responders experienced psychiatric adverse events.
	Other adverse effects, including anemia and ophthalmologic problems, were also more frequent in responders compared with non-responders.
	Decline in CD4 cell count also strongly correlated with HCV RNA decline.

Based on these findings the study authors concluded, "Our study demonstrates coupling of antiviral effect and occurrence of adverse events in HIV/HCV coinfected patients."

"These patients with interferon-related adverse effects need a multidisciplinary treatment approach, hence, they are more likely to achieve sustained virologic response," they continued. "Future studies are needed to evaluate the factors that predict the development of interferon-alpha-dependent adverse events before therapy."

Interestingly, virological response was linked to side effects of both interferon (e.g., depression) and ribavirin (e.g., anemia). Occurrence of adverse events may be an indicator that the drugs are reaching adequate levels in the body. They may also show that treatment is triggering a strong immune response against HCV -- similar to how people who experience symptoms during acute HCV infection are more likely to spontaneously clear the virus without treatment.

Laboratory of Immunoregulation & Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases; National Institute of Mental Health; National Eye Institute; Critical Care Medicine Department, Clinical Research Center, National Institutes of Health, Bethesda, MD.

Reference
A Osinusi, JJ Rasimas, R Bishop, and others. HIV/Hepatitis C Virus-Coinfected Virologic Responders to Pegylated Interferon and Ribavirin Therapy More Frequently Incur Interferon-Related Adverse Events than Nonresponders Do. Journal of Acquired Immune Deficiency Syndromes (Abstract). January 23, 2010 (Epub ahead of print).