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Differing HCV Response Rates Depending on HIV in Prospective German Cohort
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Tenth International Congress on Drug Therapy in HIV Infection, November 7-11, 2010, Glasgow
Mark Mascolini
Early virologic response and end-of-treatment response to peginterferon alfa-2a (PegIFN) plus ribavirin were similar in German hepatitis C virus (HCV) patients with or without HCV infection [1]. But preliminary results from this prospective cohort study found much lower sustained virologic response rates in HCV genotype 2/3-infected people with HIV than in the HIV-negative group. And only one third in each group had a sustained virologic response if they were infected with less responsive HCV genotypes. Jurgen Rockstroh (University Clinic, Bonn), who presented the results, suggested study-related reasons for these findings.
This prospective German cohort, the largest chronic HCV cohort in the world, includes 351 people with HIV and 5392 HIV-negative people with HCV. Respective numbers who have completed 4 weeks, 12 weeks, and a complete course of PegIFN plus ribavirin are 295 and 4718, 277 and 4491, and 169 and 3270. Everyone had HCV infection for at least 1 year.
Among people who have completed their course of therapy, 84.6% in the coinfected group and 62.1% in the HCV-only group are men. A higher proportion of the HCV/HIV group got infected with HCV sexually (52.1% versus 4.0%), and a higher proportion of the HCV-only group got infected by injecting drugs (45.9% versus 27.2%). Average age is similar in the two groups: 41.6 +/- 8.4 with HCV/HIV and 42.1 +/-11.6 with HCV only.
Average duration of HCV infection measured 6.7 years in the HCV/HIV group and 12.8 years in the HCV-only group. A slightly higher proportion in the HCV-only group was taking their first anti-HCV regimen (89.3% versus 82.8%). A higher proportion of HCV/HIV-infected people had poorly responding HCV genotypes 1, 4, 5, or 6 (81.1% versus 60.7%), while a higher proportion of HCV-monoinfected people had more responsive genotypes 2 and 3 (39.3% versus 18.9%).
Rapid virologic response rates (undetectable HCV RNA after 4 weeks of treatment) were similar in the HCV/HIV group and the HCV-only group for the hard-to-treat genotypes and somewhat worse in the HCV/HIV group for genotypes 2 and 3:
-- HCV/HIV genotypes 1/4/5/6: 26.5%
-- HCV only genotypes 1/4/5/6: 29.8%
-- HCV/HIV genotypes 2/3: 64.0%
-- HCV only genotypes 2/3: 78.7%
Early virologic response rates (undetectable HCV RNA or at least a 100-fold drop in HCV RNA after 12 weeks of treatment) were similar in the coinfected and monoinfected groups regardless of genotype:
-- HCV/HIV genotypes 1/4/5/6: 64.5%
-- HCV only genotypes 1/4/5/6: 73.0%
-- HCV/HIV genotypes 2/3: 77.8%
-- HCV only genotypes 2/3: 85.0%
End-of-treatment response rates (undetectable HCV RNA at the end of treatment) were also similar in the two groups:
-- HCV/HIV genotypes 1/4/5/6: 64.9%
-- HCV only genotypes 1/4/5/6: 70.6%
-- HCV/HIV genotypes 2/3: 96.4%
-- HCV only genotypes 2/3: 89.5%
But sustained virologic response rates (undetectable HCV RNA 24 weeks after the end of treatment) were much worse in the HCV/HIV group infected with the more responsive 2 and 3 genotypes, and low proportions in both groups responded if they had the less-responsive genotypes:
-- HCV/HIV genotypes 1/4/5/6: 34.1%
-- HCV only genotypes 1/4/5/6: 36.8%
-- HCV/HIV genotypes 2/3: 30.8%
-- HCV only genotypes 2/3: 56.3%
Rockstroh urged restraint in interpreting the sustained virologic response (SVR) results because relatively few cohort members have reached SVR and because it remains unclear whether early withdrawal affected SVR. He noted that European guidelines call for 48 weeks of PegIFN/ribavirin in people without an early virologic response; so he surmised that some people may have stopped therapy with an undetectable HCV load at 36 or 40 weeks because the patient and physician decided that treatment had lasted long enough.
Discontinuation rates were 47% in the HCV/HIV group and 32% in the HCV-only group. Cohort investigators classified reasons for discontinuation as nonresponse (55.0% with HIV/HCV and 46.8% with HCV alone), patient request (25.0% and 13.7%), tolerability (12.5% and 10.6%), and adherence problems (11.3% and 9.9%). (More than one reason could apply to a single person.)
The investigators suggested that "a more detailed analysis, in particular the influence of HIV antiretroviral therapy on HCV therapy outcome, may help [in] interpreting these data." Most HIV-infected cohort members (86.4%) were taking antiretroviral therapy, and 64.6% had an HIV load below 50 copies.
Reference
1. Baumgarten A, Lutz T, Kreckel P, et al. Efficacy and safety of peginterferon alfa-2a + RBV in cHCV/HIV vs. cHCV infected patients--interim analysis of a multicentric Germany cohort. Tenth International Congress on Drug Therapy in HIV Infection. November 7-11, 2010. Glasgow. Abstract O314.
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