Black HIV/HCV Coinfected Patients Experience Slower HCV Decline and Are Less Likely than Whites to Respond to Hepatitis C Treatment

		SUMMARY: HIV/HCV coinfected African-Americans experience significantly slower HCV viral load decline compared with white patients after starting hepatitis C treatment, indicating reduced sensitivity to pegylated interferon despite achieving equally high concentrations in the body, according to research reported in the November 27, 2009 issue of AIDS.

By Liz Highleyman

A consistent body of evidence shows that people of African descent do not respond as well as white patients to interferon-based therapy for chronic hepatitis C, though the reasons for this discrepancy are not well understood. Differences in treatment response have been less extensively studied in HIV/HCV coinfected individuals.

In the present study, Avidan Neumann from Bar-Ilan University in Israel and colleagues sought to characterize the relationship between various pharmacokinetic and pharmacodynamic parameters and virological response among HIV positive patients coinfected with HCV genotype 1 who were treated with pegylated interferon alfa-2b (PegIntron) plus ribavirin.

The researchers also hoped to learn more about the underlying mechanisms leading to poorer response in African-American versus white patients, and how these compare with findings observed in hepatitis C monoinfected individuals.

Results

	An HCV RNA decline of more than 1.0 log at day 3 combined with viral load < 5.0 log IU/mL at day 28 predicted sustained virological response (SVR).
	Negative predictive value and positive predictive value were both 100%.
	African-Americans had significantly slower HCV viral kinetics compared with white patients (P < 0.01).
	Pegylated interferon concentrations and pharmacokinetic parameters -- including maximum concentration and half-life -- were similar in both racial groups, and did not predict sustained response.
	However, the pegylated interferon EC50 (50% effective concentration), estimated from viral kinetics and drug concentration data, showed that coinfected blacks had less sensitivity to interferon than whites, thus producing slower HCV decline.
	A combined pharmacokinetic/pharmacodynamic parameter calculated as the pegylated interferon maximum concentration divided by the EC90 (90% effective concentration) was an "excellent" predictor of SVR.

These findings, the study authors concluded, show the importance of maintaining pegylated interferon alfa-2b levels above the EC90 to achieve successful treatment outcomes.

"Further studies are needed to evaluate whether these pharmacodynamic predictions are a result of differential host response to [pegylated interferon alfa-2b] or other viral factors conferring relative resistance to [pegylated interferon alfa-2b]," they added.

Bar-Ilan University, Ramat-Gan, Israel.

1/05/10

Reference
L Rozenberg, BL Haagmans, AU Neumann, and others. Therapeutic response to peg-IFN-alpha-2b and ribavirin in HIV/HCV co-infected African-American and Caucasian patients as a function of HCV viral kinetics and interferon pharmacodynamics. AIDS 23(18): 2439-2450 (Abstract). November 27, 2009.