The purpose of this study is to evaluate the efficacy and tolerability of DAA-based
regimens in the clinical practice in HIV/HCV-coinfected patients.

Hypothesis: The efficacy and tolerability of DAA-based regimens in the clinical practice
is different to what is observed in clinical trials in HIV/HCV-coinfected patients.

Real-life Security and Efficacy of DAA-based Therapy in HCV/HIV-Coinfected Patients

Hepatitis C, Chronic

Human Immunodeficiency Virus

Treatment strategies aimed to achieve sustained virologic response (SVR) are of highest
priority in patients with chronic hepatitis C and HIV coinfection, since SVR leads to a
dramatic reduction in the incidence of hepatic decompensations and mortality in this
setting. Until recently, therapy against hepatitis C virus (HCV) was based on pegylated
interferon (peg-IFN) plus ribavirin (RBV). This combination prompt SVR only in
approximately 50% of the HCV genotype 1 (HCV-1)-infected patients. Furthermore, it is
costly and associated with multiple and sometimes serious side effects. In the setting of
HIV/HCV-1-coinfection, rates of SVR are even lower and do not exceed 25% in the clinical
practice.

Considerable increases of SVR have been achieved recently with the arrival of direct
acting antivirals (DAA) against HCV. Among the first of these new agents are the protease
inhibitors telaprevir (TVR) and boceprevir (BOC), which are approved for HCV-1 infection.
Data obtained from clinical trials have demonstrated that the combination of peg-IFN/RBV
with TVR or BOC significantly augments SVR rates as compared to what is observed with
peg-IFN plus RBV only. As a consequence, triple therapy including peg-IFN, RBV plus TVR
or BOC has become the standard therapy for HCV-1-infected patients in our setting. In
addition, a number of further DAAs are currently in the final phases of development, as
it is the case for the protease inhibitors faldaprevir and simeprevir, the polymerase
NS5B inhibitor sofosbuvir and the NS5A inhibitor daclatasvir.

Although the considerable improvement of therapy outcome with DAA-including regimens is
giving a positive prospective, there are a number of questions that have to be solved as
soon as possible. On the one hand, the information on response to DAA in the coinfected
population is derived from clinical trials, which often do not reflect patient management
in the clinical practice. Also, the populations included in clinical trials are highly
selective and may lack the high proportion of difficult-to-treat individuals expected
among the candidate population, i.e., those who failed previous treatment and who bear
compensated cirrhosis. In fact, data derived from the French cohort CUPIC including
HCV-monoinfected, cirrhotic patients, show that tolerability and efficacy of TVR and
BOC-based treatment is lower than observed in pivotal trials. On the other hand, similar
to dual therapy including Peg-IFN/RBV, it is possible that both response rates and safety
profiles of DAAs are not comparable between HCV-monoinfected and HIV/HCV-coinfected
patients. In this context, the coinfected population has singularities as the
coadministration of antiretroviral therapy, that may cause drug-drug-interactions and
decreased tolerability, thus resulting in diminished efficacy. Finally, it is of highest
relevance to identify predictive factors for treatment response in the new DAA-based
regimens in order to individualize treatment decision and duration of therapy.

Due to the above mentioned, studies on safety and efficacy of DAA-based therapy under
real life conditions in HIV/HCV-coinfected patients are urgently needed.

Primary objectives:

  -  To determine the efficacy of DAA-based therapy in the clinical in patients with
     chronic hepatitis C and HIV coinfection.

  -  To determine the security of DAA-based therapy in the clinical in patients with
     chronic hepatitis C and HIV coinfection.

Secondary objectives:

  -  Identification of predictive factors for response to DAA-based treatment in the
     studied population.

  -  Compare security and efficacy of the different DAAs used.

  -  Evaluate the on-treatment HCV kinetics for the different regimens.

Scheduled visits: 0, 1, 2, 4, 8, 12, 24, 36 and 48 weeks, as well as 12 and 24 weeks
post-treatment.

Definition SVR: Undetectable HCV-RNA 24 weeks after scheduled end of treatment.

Definition of hepatic fibrosis:

  -  advanced fibrosis: F3 as determined by liver biopsy or 11 kilopascals as determined
     by transient elastometry

  -  cirrhosis: F4 as determined by liver biopsy or 14.6 kilopascals as determined by
     transient elastometry

Variables collected within in the cohort:

  -  primary outcome variable: SVR (efficacy study) and % of patients who discontinued
     therapy due to adverse events (safety study)

  -  epidemiological variable: age, sex, interleukin 28B rs12979860 genotype

  -  variables related to hepatitis C virus-infection: infection route, genotype, grade
     of hepatic fibrosis and method used for its determination, baseline
     Child-Pough-Index, previous hepatic decompensations

  -  treatment-related variables: previous response to treatment, doses and dose
     reductions/discontinuations of peg-IFN, RBV and the DAA(s), overall severe adverse
     events, adverse events that occur in more than 5% of the patients, hepatic
     decompensations, deaths, HCV viral load at baseline and at each visit

  -  variables related to HIV-infection: Centers for Disease Control and Prevention (CDC)
     category, HIV viral load, cluster of differentiation 4 (CD4) cell count,
     antiretroviral regimen

  -  analytical variables: aspartate aminotransferase (AST), alanine aminotransferase
     (ALT), platelets, leucocytes, low-density lipoprotein cholesterol, bilirubin,
     gamma-glutamyltransferase (GGT), alkaline phosphatase,

  -  clinical variables: alcohol intake Quality assurance and data checks: Data will be
     obtained from controlled databases at the participating centers. Databases will be
     monitored and controlled by queries every three months. Descriptive statistics will
     be be applied in order to detect transcription errors.

Source data verification: not planned.

All grade 3 or 4 adverse events, as well as all unexpected events, will be reported to
the Andalusian Center for Pharmacovigilance (Centro Andaluz de Farmacovigilancia,
www.cafv.es).

A sample size of 230 is planned for this study.

Statistical analysis: The outcome variables of this study will be the achievement of SVR,
as well as the development of severe adverse events during follow-up. Descriptive
statistical analysis will be performed in order to describe the cohort. Continuous
variables will be expressed as median [interquartile range (IQR)] and categorical
variables as number [percentage; 95% confidence interval (CI)]. The association of
continuous variables with SVR or the frequency of patients who discontinue therapy will
be analyzed using the Student's t-test for normal distribution and the Mann-Whitney
U-test otherwise whereas the relationship with categorical variables will be determined
applying the χ2-test or the Fisher's test, when applicable. Those factors that show an
association in the univariate analysis with a p<0.2, as well as those with a biologically
possible influence, will be entered logistic regression in order to identify independent
predictors for SVR. The adjusted odds ratio (AOR) and the respective 95% CI will be
calculated. All p values <0.05 will be considered statistically significant. Data will be
analyzed using the SPSS statistical software package release 19.0 (SPSS Inc., Chicago,
Illinois, USA) and STATA 9.0 (StataCorp, College Station, Texas, USA).

Sample size calculations: Estimating a SVR rate of 55%, with a confidence interval of 95%
and a lost-to-follow-up rate of 5%, a minimum of 230 patients should be included in order
to obtain a precision of 5%.

DAA against HCV

Security and Efficacy of Triple Therapy Including Direct-Acting Antivirals Against Chronic Hepatitis C Infection In HIV-Coinfected Patients In Real-Life Conditions: The Prospective HEPAVIR Cohort.

Achievement of SVR to DAA-based therapy in the clinical practice in patients with chronic
hepatitis C and HIV coinfection.

Development of severe adverse events related to DAA-based therapy in the clinical
practice in patients with chronic hepatitis C and HIV coinfection.

In order to compare TVR- and BOC-based therapy, the numbers of patients who achieve SVR
to DAA-based therapy will be analyzed.

In order to compare TVR- and BOC-based therapy, the numbers of patients who develop
adverse events during either treatment will be analyzed.

The numbers of patients who achieve SVR to DAA-based therapy in absence of interferon
will be analyzed.

HIV/HCV-coinfected patients who start therapy against HCV including one or more DAA

Real-life Security and Efficacy of DAA-based Therapy in HCV/HIV-Coinfected Patients

About this trial

Study ID

Status

Type

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?

Locations

Location

Status