Study design
This was a cross-sectional study. The data was collected using Estonian HIV Cohort Study (E-HIV) which is a web-based database established in 2009 and comprises HIV positive subjects aged > 16 years since 1992(13). In Estonia, all HIV positive patients are treated by infectious diseases specialists in five HIV treatment centres (West-Tallinn Central Hospital, Tartu University Hospital, Ida-Virumaa Central Hospital, Narva Hospital and Pärnu Hospital) and in all four prisons. Participation in E-HIV is offered to all HIV positive subjects at the first visit to infectious disease specialist. The participation in E-HIV is voluntary and written informed consent is requested from all participants. The data are first entered during the first visit and then updated at each visit to the physician, subjects infected before 2009 were entered retrospectively. Data are updated at each visit. E-HIV collects sociodemographic (gender, age, route of HIV transmission), clinical data (cART history, opportunistic diseases, comorbidities including presence of HCV infection) and outcome together with date and reason of death as described elsewhere (13).
In this study we have compared two time periods – first, from 1st of January 2000 to 31st of December 2008 when HIV epidemic was mostly spreading among PWID and second, from 1st of January 2009 to 31st of December 2015 when HIV started to emerge to general population.
Study Population
We made data extraction on the 1st of August 2016 and included all HIV positive patients who have been entered into database during the study period. The following information was analysed: gender, date of birth, date of the first positive HIV test, HCV seropositivity and/or HCV PCR positivity and/or viral load year together with time of the first positive HCV test, self-reported route of HIV transmission, HCV genotype and treatment history, CD4 + T cell count and HIV-1 viral load (VL) at the first visit.
Definitions
HIV positivity was defined as having a confirmed test performed in Estonian HIV Reference Laboratory at West Tallinn Central Hospital using INNO-LIA® HIV I/II Score (Innogenetics N.V., Gent, Belgium), Bio‐Rad's NEW LAV BLOT I (Bio‐Rad Laboratories Inc., Hercules, CA, USA) and NEW LAV BLOT II (Bio‐Rad Laboratories Inc., Hercules, CA, USA) tests.
HCV positivity was defined as follows: positive HCV antibody test and/or positive HCV RNA and/or determination of HCV genotype and/or treatment for HCV infection. Subjects who had negative HCV antibody test were considered as HCV negative; subjects who had no information about HCV testing were designated as HCV unknown.
The prevalence of HIV/HCV co-infection and the genotypic distribution were calculated based on the year of HIV diagnosis because all HIV positive subjects are always tested for HCV infection whereas date of HCV infection may not be known.
HCV genotype was determined when the patient had medical insurance and was eligible for HCV treatment. In case of repeated HCV testing all GTs were reported with the date of each test. If the GT was determined as GT 1 at first but repeated and determined as 1a or 1b only the latter was reported.
The HIV transmission route was self-reported. Patients with no information were designated as “undetermined”. If route of transmission was reported heterosexual and PWID simultaneously, the latter was considered as most likely route of transmission.
Statistical analysis
Exact binomial 95% confidence intervals (CI) were calculated for the prevalence of HIV/HCV coinfection for each year. To estimate the change in prevalence of HIV/HCV co-infection between two time periods modified Poisson regression model was fitted and results reported as prevalence ratio with corresponding 95% CI (18,19). Sociodemographic characteristics of HIV/HCV co-infected and HIV mono-infected patients were expressed as median and interquartile range (IQR) or proportions (absolute and relative frequencies) and compared using Wilcoxon rank-sum test for continuous and Chi-square or Fisher exact test for categorical variables. To account for the multiple testing, p-values were adjusted using Holm-Bonferroni method. To further examine the association between HIV/HCV coinfection and patient characteristics – age, gender, transmission route and period of HIV diagnosis, adjusted prevalence ratios with 95% CI were calculated from modified regression models.
Analysis were run on complete case basis and prevalence of HIV/HCV co-infection was assumed to be the same among patients with unknown HCV status as patients with known HCV status.
Statistical analyses were performed in Stata version 14.2 (20).
Ethical Aspects
E-HIV is approved by the Ethics Committee of Tartu University. All the patients have signed informed consent to participate in the cohort.