Elsevier

Journal of Hepatology

Volume 63, Issue 3, September 2015, Pages 573-580
Journal of Hepatology

Research Article
High hepatic and extrahepatic mortality and low treatment uptake in HCV-coinfected persons in the Swiss HIV cohort study between 2001 and 2013

https://doi.org/10.1016/j.jhep.2015.04.019Get rights and content

Background & Aims

The landscape of HCV treatments is changing dramatically. At the beginning of this new era, we highlight the challenges for HCV therapy by assessing the long-term epidemiological trends in treatment uptake, efficacy and mortality among HIV/HCV-coinfected people since the availability of HCV therapy.

Methods

We included all SHCS participants with detectable HCV RNA between 2001 and 2013. To identify predictors for treatment uptake uni- and multivariable Poisson regression models were applied. We further used survival analyses with Kaplan-Meier curves and Cox regression with drop-out as competing risk.

Results

Of 12,401 participants 2107 (17%) were HCV RNA positive. Of those, 636 (30%) started treatment with an incidence of 5.8/100 person years (PY) (95% CI 5.3–6.2). Sustained virological response (SVR) with pegylated interferon/ribavirin was achieved in 50% of treated patients, representing 15% of all participants with replicating HCV-infection. 344 of 2107 (16%) HCV RNA positive persons died, 59% from extrahepatic causes. Mortality/100 PY was 2.9 (95% CI 2.6–3.2) in untreated patients, 1.3 (1.0–1.8) in those treated with failure, and 0.6 (0.4–1.0) in patients with SVR. In 2013, 869/2107 (41%) participants remained HCV RNA positive.

Conclusions

Over the last 13 years HCV treatment uptake was low and by the end of 2013, a large number of persons remain to be treated. Mortality was high, particularly in untreated patients, and mainly due to non-liver-related causes. Accordingly, in HIV/HCV-coinfected patients, integrative care including the diagnosis and therapy of somatic and psychiatric disorders is important to achieve mortality rates similar to HIV-monoinfected patients.

Introduction

The treatment of hepatitis C virus (HCV) infection in HIV-infected patients has changed dramatically in the last decades. Before 1990, HCV-infection was incurable. Subsequently, sustained viral response (SVR) was only about 10% with interferon monotherapy [1]. After 2000, and until recently, the pegylated interferon and ribavirin (pegIFN/RBV) combination therapy improved outcome substantially, but still resulted in modest SVR of 14–29% for genotype 1, and 44–73% for genotypes 2 or 3 [2], [3], [4]. Although successful treatment of chronic HCV-infection decreased liver-specific and all-cause mortality [5], [6], rates of treatment uptake in the HIV-coinfected population were low [7]. Barriers to start treatment included comorbid medical and psychiatric conditions, active substance abuse with the inability to adhere to complex HCV treatment regimens, expected adverse effects of or contraindications for HCV combination therapy, and uncontrolled HIV disease (reviewed in [7]).

With the availability of direct-acting antivirals (DAAs), the landscape of HCV treatment is changing rapidly. New treatment options with high cure rates for HIV/HCV-coinfected patients are now available or will be approved shortly. At the beginning of this new era, documentation of the long-term epidemiological trends, treatment uptake, outcome and mortality of HCV-infections is important to adequately assess the impact of new therapies. Moreover, physicians and public health authorities need information on the proportion of patients with replicating HCV-infection, on HCV genotype distribution and on liver-related complications in representative populations. This information is key to define the most urgent treatment priorities, and to optimally invest the available resources in order to reduce HCV-related mortality in HIV-infected patients.

The Swiss HIV Cohort Study (SHCS) offers an ideal platform to study the natural course of HCV-infection and long-term influence of HCV treatments in a nationwide representative population of HIV-infected patients. We aimed to (i), assess the changes in epidemiology, clinical course and therapy of HCV-infections between 2001 and 2013, and (ii), to characterize the population who remains eligible for the new HCV treatment options by the end of 2013.

Section snippets

Swiss HIV cohort study

The SHCS is an ongoing, prospective cohort study that continuously enrolls and observes HIV-infected adults at five university outpatient clinics, two large district hospitals, affiliated regional hospitals, and private practices, since 1988. This nationwide cohort covers 69% of all patients living with AIDS, and 75% of persons receiving antiretroviral therapy (ART) in Switzerland [8], [9]. Demographic, clinical and laboratory data are collected at registration and every six months thereafter

Study population

Of 12,401 SHCS participants followed between 1 January 2001 and 31 December 2013, 2956 (23.8%) were HCV antibody positive, and 2107 (17.0%) were HCV RNA positive (Fig. 1). In 415 patients HCV RNA was not available (Fig. 1). Of those, 42.0% died and 39.5% left the cohort in the first years after the approval of pegIFN/RBV therapy in Switzerland, in a time period where HCV RNA was not collected systematically. HCV RNA tested vs. HCV RNA untested patients did not differ regarding sex, age, and HIV

Discussion

This is one of the largest nationwide community based HIV cohort studies describing the long-term changes in epidemiology, treatment uptake, efficacy, and mortality of HCV-coinfection since the availability of HCV treatment. We found that of 12,401 cohort participants 24% were HCV-seropositive and 17% were HCV RNA positive. Of those with replicating HCV-infection, 30% were treated and 15% were cured during a follow-up period of thirteen years. During the observation period 16% of participants

Financial support

This study was funded within the framework of the SHCS, supported by the Swiss National Science Foundation – Switzerland (grant # 134277), and with an unrestricted grant by Gilead Sciences.

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Author’s contributions

HK, BL, RW and AR concepted and designed the study. HK, MC, JA, AB, MS, EB, RW and AR were responsible for the data acquisition. BL analyzed the data. All authors interpreted the data. HK and AR prepared the paper. All authors read and approved the final manuscript.

Acknowledgments

This study was funded within the framework of the SHCS, supported by the Swiss National Science Foundation (grant # 134277), and with an unrestricted grant by Gilead Sciences.

The members of the SHCS are: Aubert V, Battegay M, Bernasconi E, Böni J, Bucher HC, Burton-Jeangros C, Calmy A, Cavassini M, Dollenmaier G, Egger M, Elzi L, Fehr J, Fellay J, Furrer H, Fux CA, Gorgievski M, Günthard H, Haerry D, Hasse B, Hirsch HH, Hoffmann M, Hösli I, Kahlert C, Kaiser L, Keiser O, Klimkait T, Kouyos R,

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