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RESEARCH LETTERS

Treatment of acute hepatitis C virus infection in HIV-infected MSM: the effect of treatment duration

Lambers, Femke AEa; Brinkman, Keesb; Schinkel, Jankec; Spijkerman, Ingrid JBd; Molenkamp, Richardc; Coutinho, Roel Ae,f; Prins, Mariaa,f; van der Meer, Jan TMf on behalf of the MOSAIC (MSM Observational Study of Acute Infection with hepatitis C) study group

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doi: 10.1097/QAD.0b013e3283480144
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Abstract

The widespread epidemic of sexually transmitted hepatitis C virus (HCV) infection among HIV-infected MSM has led to an increased number of early diagnoses of HCV infection and accordingly acute HCV treatment [1]. Although treatment of acute HCV in HIV-coinfected can be quite as successful as treatment of chronic HCV monoinfection [2–7], discussion is ongoing as to the optimum treatment strategy and specifically treatment duration for this specific population [8]. Our objective was therefore to examine the HCV treatment outcome and the effect of treatment duration among HIV-infected MSM with acute HCV infection in two hospitals in Amsterdam.

We included HIV-infected MSM diagnosed with an acute HCV infection presumably transmitted by male-to-male sexual contact; less than 2 years between the last negative result (HCV antibody or RNA) and the first positive result; and less than 2 years between estimated time of infection (midpoint between last negative and first positive test) and start of treatment. In one hospital, treatment was started with the intention to treat 24 weeks, in the other with the intention to treat 48 weeks. In both hospitals, regimens consisted of weekly peginterferon (Peg-IFN)-alpha-2a (180 μg/week) or (Peg-IFN)-alpha-2b (1.5 μg/kg bodyweight/week) and weight-based ribavirin daily.

Data collection included clinical data and the HCV virological response at week 4 (rapid virological response: RVR), week 12 (early virological response: EVR), at the end of treatment and 24 weeks after treatment; the latter defining treatment outcome as a sustained virological response (SVR) when HCV-RNA was undetectable. Logistic regression analysis was performed to examine the associations between different variables, including treatment duration, and treatment outcome.

Of 84 patients treated between 2003 and 2009, 52 met the inclusion criteria for this study, of whom two spontaneously cleared the virus and were excluded from analyses. Of the remaining, 42% (21/50) started treatment with the intention to treat 24 weeks and 58% (29/50) with the intention to treat 48 weeks. Nevertheless, treatment duration was not always exactly as intended, with the shorter regimen ranging from 22 to 36 weeks [median 24 weeks, interquartile range (IQR) 23–25] and the longer regimen ranging from 47 to 58 weeks (median 48 weeks, IQR 48–50).

Table 1 presents the clinical and virological characteristics, and determinants of treatment outcome of the 50 MSM at start of treatment.

T1-12
Table 1:
Characteristics of HIV-infected MSM with acute HCV infection treated in two hospitals in Amsterdam, from 2003 through 2009, and determinants of treatment outcome.

Of the 50 patients, 12% (6/50) were either nonresponders who stopped treatment around week 12 (n = 3) or persons who stopped earlier because of side-effects (n = 3). At the end of treatment, 88% (44/50) of patients were HCV-RNA negative, of whom 38 subsequently showed SVR and six relapsed. Overall, 76% (38/50) [95% confidence interval (CI) 64–88] obtained SVR. Virological data at week 4 and/or week 12 of treatment were available for 70% (n = 35) and 78% (n = 39) of the patients, respectively. An RVR was present in 19 of 35 patients (54%), of whom 18 achieved SVR (positive predictive value 95%). An EVR was present in 34 of 39 patients (87%), of whom 29 achieved SVR (positive predictive value 85%). In those without RVR, the negative predictive value was 44% (7/16); for those without EVR, it was 100%. Of patients without RVR and treated for 24 weeks, 40% (2/5) had SVR; among those without RVR and treated for 48 weeks, SVR was 64% (7/11) (P = 0.377).

In univariate analysis, no significant effect of longer treatment duration on SVR was found [odds ratio (OR) 1.53; 95% CI 0.42–5.66]. After adjusting for genotype, time between estimated infection and starting treatment, and RVR (see Table 1), the effect increased but remained nonsignificant (OR adjusted 2.23; 95% CI 0.43–11.46). RVR was significantly associated with SVR in both univariate and multivariate analysis. Because of correlation, EVR was only studied in univariate analysis.

Finally, a sensitivity analysis showed that the effect of treatment duration on outcome did not change substantially when analysis was restricted to patients with less than 1 year (n = 40) or less than 6 months (n = 19) between negative and positive HCV test and between estimated infection and start of treatment.

The high SVR rate of 76% in this study confirms that treatment of HCV infection can be successful in HIV-infected patients when started in the acute phase and should encourage clinicians to treat this complicated patient group. Although the adjusted odds of attaining SVR was 2.2 times higher for 48 weeks of treatment compared with 24 weeks, this difference was not statistically significant. This suggests that 24 weeks of treatment might be sufficient. This result strengthens the evidence for recommendations in current treatment guidelines for acute HCV infection in HIV coinfected patients [8–10]. The shorter regimen would be of great advantage for patients, as both peginterferon and ribavirin can cause serious side-effects.

High (pretreatment) CD4 cell counts have been found to be associated with spontaneous clearance and SVR in genotype 1 HCV-infection [11,12]. Like Vogel et al.[7], we could not confirm this association. However, the majority of our patients had relatively high CD4 cell counts, making it difficult to demonstrate a potential effect of immunodeficiency. Our study also found no influence of concurrent cART, which suggests that coinfected patients with sufficient CD4 cell counts do not necessarily need to start cART before starting HCV treatment. Like others, we found that RVR and EVR are the strongest predictors for SVR [5,7].

Even though our sample size is limited, our study is one of the largest to be undertaken by one group and results are comparable with that of the larger European multicentre cohort study [7]. Larger prospective studies are still of interest to specify new determinants for treatment decision guidance, such as the IL28b polymorphism [13–15].

In conclusion, the results of this retrospective cohort of HIV-infected MSM with acute HCV infection demonstrate that acute HCV treatment in this coinfected population can be very effective and 24 weeks treatment may be sufficient. The week 4 and 12 virological responses were strong predictors for good outcome and its role in clinical decision-making should be studied more extensively besides other predictors.

Acknowledgements

The following individuals also contribute to the MOSAIC study group: H. Reesink (Academic Medical Center Amsterdam); D. van Baarle (University Medical Center Utrecht); and C. Smit (HIV Monitoring Foundation Netherlands).

We would like to thank G. van den Berk, W. Koevoets and S. van Mens for data collection; S. Jurriaans and M. Bakker for sample management, and L. Phillips for editorial review.

This study is funded by the AIDS Fund Netherlands, grant no. 2008026.

All authors attributed to the idea and design of the study. J.M. and K.B. treated patients and collected clinical data; J.S., R.M. and I.S. performed virological tests and collected virological data; F.L. collected data and F.L. and M.P. performed statistical analyses. F.L. drafted the manuscript., which was reviewed and edited by all authors. All the authors have approved the text as submitted to the journal.

Data (in part) were presented previously at 17th Conference on Retroviruses and Opportunistic Infections, San Francisco 2010. Sixth international workshop on HIV and Hepatitis Co-infection, Tel Aviv, 2010 and published as abstract in Reviews in Antiviral Therapy and Infectious Diseases, Volume 4, 2010.

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