HIV/HCV co-infection in Sweden : epidemiology, HCV treatment and the importance of IL28B gene polymorphism

Liver disease, mainly due to hepatitis C virus (HCV) infection, is a leading cause of death in HIV positive patients with access to antiretroviral therapy (ART). HCV treatment, which can prevent long-term complications of HCV infection, is available. Despite this, only a minority of HIV/HCV co-infected patients initiate HCV treatment. We aimed to determine key epidemiological features, including HCV treatment uptake, of HIV/HCV co-infection in Sweden.

In 2009, the IL28B genotype was shown to be strongly associated with spontaneous and treatment induced clearance of HCV genotype 1. Patients with HCV genotype 2/3 and HIV co-infection were less studied. We therefore aimed to study the role of IL28B genotype in these sub-groups of HCV infected patients.

In paper I and II, 13 HIV/HCV co-infected and 100 HCV mono-infected patients with HCV genotype 2/3 were treated with a lower-than-standard dose of pegylated interferon and weight-based ribavirin. Early viral kinetics and treatment outcome were studied according to IL28B genotype. In HCV mono-infected patients, IL28B genotype CC was associated with a steeper first phase decline during HCV treatment. This did not translate into higher sustained viral response (SVR) rates, hence the value of pretreatment IL28B genotyping can be questioned in patients with HCV genotype2/3. The small number of HIV/HCV co-infected patients included prevents firm conclusions regarding this group.

In paper III and IV, data from InfCare HIV, where all known HIV infected persons in Sweden (n=5315) are included, were extracted. Factors associated with spontaneous clearance of HCV and HCV treatment were studied in uni- and multi-variate analyses. Furthermore, using a questionnaire given to HIV/HCV co-infected patients and their attending physicians in Stockholm, we investigated reasons for not having initiated HCV treatment yet.

The prevalence of anti-HCV in the total HIV infected Swedish cohort was 14% in 2010. This corresponds to a 9-11% prevalence of chronic HCV. 21% had spontaneously cleared the HCV infection. Spontaneous clearance of HCV was associated with IL28B genotype CC and a chronic hepatitis B virus infection. Interestingly, three cases of spontaneous clearance of a chronic HCV infection after immune reconstitution induced by ART were seen, all with IL28B genotype CC. The HCV treatment uptake was 25%, which is in line with European data and possibly also with the treatment uptake in HCV mono-infected patients in Sweden. HCV genotype 2/3, HIV transmission route other than intravenous drug use (IDU) and on-going ART were associated with a higher HCV treatment uptake. No significant differences in treatment uptake according to gender, ethnicity or university clinic or not were found. A major reason for not having initiated HCV treatment was on-going or recent IDU. The higher HIV treatment uptake, and rate of undetectable HIV viral load, indicate that many patients who had not initiated HCV treatment were adherent to their HIV treatment. When interferon-free direct acting antivirals (DAA) combinations soon will become available, this changes everything. Again. HCV treatment should then expand to include more HIV/HCV co-infected patients in order to prevent morbidity and mortality from HCV in this population.

List of scientific papers

I. Nilsson J, Weiland O. Effect of control selection on sustained viral response rates in genotype 2/3 HCV mono-infected versus HIV/HCV co-infected patients. Scandinavian Journal of Infectious Diseases. 2010; 42:533-539.
https://doi.org/10.3109/00365541003621486

II. Stenkvist J, Sönnerborg A, Weiland O. HCV RNA decline in chronic HCV genotype 2 and 3 during standard of care treatment according to IL28B gene polymorphism. Journal of Viral Hepatitis. 2013; 20:193-199.
https://doi.org/10.1111/j.1365-2893.2012.01645.x

III. Stenkvist J, Nyström J/ Falconer K, Sönnerborg A, Weiland O. Spontaneous clearance of chronic HCV in HIV/HCV co-infected patients with ART induced immune reconstitution. [Submitted]

IV. Stenkvist J, Weiland O, Sönnerborg A, Blaxhult A, Falconer K. Lower uptake of HCV treatment than HIV treatment in HIV/HCV co-infected patients. [Submitted]