SUMMARY: HIV positive people with normal levels of the liver enzyme alanine aminotransferase (ALT) who received hepatitis C therapy using pegylated interferon plus ribavirin responded as well as individuals with elevated ALT, according to findings presented at the XVIII International AIDS Conference (AIDS 2010) last month in Vienna.

By Liz Highleyman

A majority of people with chronic hepatitis C virus (HCV) infection will not progress to advanced liver disease such as cirrhosis or hepatocellular carcinoma, but a larger proportion will develop some degree of liver fibrosis, and research indicates that progression is more likely among HIV/HCV coinfected individuals than among those with HCV alone.

People with signs of liver disease progression are typically advised to receive treatment. Liver biopsy is the "gold standard" for determining extent of liver damage, but elevated ALT -- a sign of liver inflammation -- is also often considered an indicator of active disease progression and need for treatment.

At last month's conference, Miguel Angel von Wichmann de Miguel from Hospital de Donostia in San Miguel, Spain, and colleagues presented data from an analysis of hepatitis C treatment in HIV/HCV coinfected patients with persistently normal ALT, a group that has been less extensively studied.

This single-arm, open-label, Phase 4 (post-market) study included 68 coinfected participants at multiple centers in Spain. Just over half (35 people, or 52%) were classified as "case" patients with normal ALT (at least 5 normal measurements over a 24-month period), with the rest (33 people, or 49%) designated "control" patients with elevated ALT (that is, the type of patients usually treated and studied).

About three-quarters were men, the median age was 43 years, most (74%) had hard-to-treat HCV genotypes 1 or 4, and just over half had high baseline HCV viral load (? 800,000 IU/mL). Almost all (89%) were on antiretroviral therapy (ART) with undetectable HIV viral load and the median CD4 cell count was 461 cells/mm3.

All participants received 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day weight-adjusted ribavirin for 48 weeks, with a 24-week post-treatment follow-up period to assess sustained virological response (SVR), or continued undetectable HCV RNA.

The AIDS 2010 report included results at week 4 (rapid virological response, or RVR) and week 12 (early virological response, or EVR); follow-up is continuing to determine SVR rates.

Results

	35% of patients in the normal ALT group achieved RVR, or undetectable HCV RNA at week 4 of therapy, compared with 33% in the elevated ALT group, not a significant difference (P = 0.99).
	EVR rates, or at least a 2-log reduction in HCV RNA by week 12, diverged a bit more -- 80% in the normal ALT and 96% in the elevated ALT group -- but the difference did not reach statistical significance (P = 0.10).
	Rates of complete EVR, or undetectable HCV RNA at week 12, were 52% and 68%, respectively, also not a significant difference.
	ALT levels decreased in both groups, but remained lower in the initially normal ALT group.
	There were no significant differences between the 2 groups with regard to safety profiles.
	46% of patients in the normal ALT group and 45% in the elevated ALT group experienced adverse events.
	Only 1 patient in each group required blood cell growth factors to manage anemia or neutropenia.
	More patients in the normal ALT group compared with the elevated ALT group (19% vs 40%, respectively) received interferon or ribavirin dose adjustments or discontinued treatment due to adverse events, but again this did not reach statistical significance (P = 0.25).

Based on these findings, the researchers concluded, "Response to peginterferon alfa-2a plus ribavirin in HIV/HCV coinfected patients with persistently normal ALT levels is comparable to those with elevated ALT levels."

Investigator affiliations: Hospital de Donostia, San Sebastian, Spain; Hospital Universitario de Bellvitge, Barcelona, Spain; Hospital La Paz, Madrid, Spain; Hospital de Cruces, Bilbao, Spain; Hospital La Princesa, Madrid, Spain; Consorci Sanitari de Terrasa, Terrasa, Spain; Hospital Clinic de Barcelona, Barcelona, Spain; Hospital General Universitario de Alicante, Alicante, Spain; Hospital Santa Creu i Sant Pau, Barcelona, Spain; Hospital Joan XXIII, Tarragona, Spain.

8/10/10

Reference
MA von Wichmann de Miguel, M Santin, J Gonzalez, and others (CONTRA). Phase IV, open label study to evaluate peginterferon alpha-2a plus ribavirin for treatment of chronic hepatitis C in HIV-infected patients with persistently normal alanine aminotransferase. XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. (Abstract).