HIV-HCV coinfected patients treated with pegylated interferon plus ribavirin achieved a sustained virological (SVR) rate of 54% -- the same as HIV negative individuals -- and sustained response was more likely in patients who did not take a nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) as part of their combination antiretroviral regimen.

By Liz Highleyman

The effect of NRTIs on response to interferon-based treatment for chronic HCV remains controversial. In particular, some studies have found that abacavir (Ziagen, also in the Trizivir and Epzicom coformulations) is associated with poorer response, but others have not observed this effect.

As reported in a poster at the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009) last month in Cape Town, German researchers conducted a prospective, partially randomized study comparing hepatitis C treatment outcomes in HIV negative individuals (Group A; n = 60), HIV positive patients not on combination antiretroviral therapy (ART) (Group B; n = 46), and HIV positive patients on ART (Group C; n = 68).

Participants in Group C were randomly assigned to take either a NRTI-free regimen consisting of dual protease inhibitors (PIs) or a PI plus a non-nucleoside reverse transcriptase inhibitor (NNRTI) (Group C1; n = 20), or else a standard HAART regimen consisting of 2 NRTIs plus a PI or NNRTI (Group C2; n = 48).

Approximately 60% of participants had hard-to-treat HCV genotypes 1 or 4. Patients were initially treated with 180 mcg pegylated interferon alfa-2a (Pegasys) plus 800 mg/day ribavirin (lower than the usual 1000-1200 mg/day weight-adjusted dose for hard-to-treat genotypes) for 24 weeks if they had HCV genotypes 2 or 3, or 48 weeks if they had genotypes 1 or 4 (guidelines recommend 48 weeks for coinfected patients regardless of genotype). The protocol was later amended to treat genotype 2 or 3 patients for 48 weeks and to increase the ribavirin dose for those with genotypes 1 or 4.

Results

	In an intent-to-treat (missing=failure) analysis, SVR rates were comparable between HIV positive and HIV negative patients, both at 54%.
	SVR rates did not differ significantly between Group B (ART) and Group C (no ART), at 59% vs 52%, respectively.
	However, there was a significant difference between patients in Group C1 (NRTI-sparing) and Group C2 (NRTI-containing), at 75% vs 42%, respectively (P = 0.031).
	In a post-hoc multivariate analysis of Group C patients according to SVR status, low baseline HCV RNA, genotype 2 or 3, and no use of abacavir were independent predictors of SVR.
	After restricting the analysis to genotype 1 or 4 patients who received weight-adjusted ribavirin, however, only baseline HCV RNA remained a significant predictor.

"High SVR rates, comparable to HIV negative patients, were reached in 55% of HIV positive patients," the investigators concluded.

NRTI-free HAART resulted in higher SVR rates compared with NRTI-containing regimens, they added, suggesting, "This effect was most likely due to use of abacavir in patients with low doses of ribavirin."

Bonn University, Bonn, German; Practice Hintsche/Klausen, Berlin, Germany; Infektiologikum Frankfurt, Frankfurt/Main, Germany; Charite University Medical Center, Berlin, Germany; University of Frankfurt, Frankfurt/Main, Germany; Ärzteforum Seestrasse, Berlin, Germany; Praxis Dupke/Baumgarten/Carganico, Berlin, Germany; Institut für Interdisziplinäre Medizin, Hamburg, Germany; University of Würzburg, Würzburg, Germany; Practice John, Berlin, Germany; Praxiszentrum Kaiserdamm, Berlin, Germany.

8/11/09

Reference
M Vogel, G Ahlenstiel, G Klausen, and others. The effect of nucleoside free HAART on the treatment of chronic HCV infection. 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa. Abstract WEPEB235. (Abstract).

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