Page 12 - EASL Recommendations on Treatment of Hepatitis C 2015 - Full version
P. 12
safety issues. Elvitegravir/cobicistat should not be used because JOURNAL OF HEPATOLOGY
of the additional boosting effect.
Recommendations
Recommendations
• Indications for HCV treatment in HCV/HIV coinfected
• Numerous and complex drug-drug interactions are persons are identical to those in patients with HCV-
possible with the HCV DAAs, especially when they monoinfection (A1)
are used in IFN-free combinations. Strict rules should
thus be applied. As the data accumulate, guidance for • Notwithstanding the respective costs of these options,
contra-indications and dose adjustments can be found IFN-free regimens are the best options when available
in Tables 4A to 4F of these Recommendations and at in HCV-monoinfected and in HIV-coinfected patients
www.hep-druginteractions.org where they are regularly without cirrhosis or with compensated (Child-Pugh A) or
updated (B1) decompensated (Child-Pugh B or C) cirrhosis, because
of their virological efficacy, ease of use and tolerability
• The use of cobicistat-based regimens, efavirenz, (A1)
etravirine, nevirapine, ritonavir, and any HIV
protease inhibitor, boosted or not by ritonavir, is not • The same IFN-free treatment regimens can be used
recommended in HIV-infected patients receiving in HIV-coinfected patients as in patients without HIV
simeprevir (A1) infection, as the virological results of therapy are
identical (A1)
• The daily daclatasvir dose should be adjusted to 30
mg daily in HIV-infected patients receiving atazanavir/ For each genotype, the available options are described below, fol-
ritonavir and to 90 mg daily in those receiving efavirenz lowed by a summary of the data available for the given option,
(B2) and summarized in Tables 5 and 6.
• No drug-drug interaction has been reported between Treatment of HCV genotype 1 infection
sofosbuvir and antiretroviral drugs (A2)
Six treatment options are available in 2015 for patients infected
• The fixed-dose combination of sofosbuvir and ledipasvir with HCV genotype 1, including two IFN-containing regimens
can be used with all antiretrovirals. However, this and four IFN-free regimens. The combination of sofosbuvir and
regimen should not be used with the combination ribavirin should not be used in patients infected with HCV geno-
of tenofovir/emtricitabine with atazanavir/ritonavir, type 1. In settings where none of the proposed options is avail-
darunavir/ritonavir, lopinavir/ritonavir or elvitegravir/
cobicistat when possible, or used with caution with able, the double combination of PegIFN-a and ribavirin, or the
frequent renal monitoring (B1) triple combination of PegIFN-a, ribavirin and either telaprevir
• The combination of ritonavir-boosted paritaprevir, or boceprevir, remain acceptable for selected patients likely to
ombitasvir and dasabuvir should not be used with respond to these regimens until new DAAs become available
efavirenz, etravirine or nevirapine, and rilpivirine and affordable; see prior EASL Clinical Practice Guidelines [5,24].
should be used cautiously with repeat ECG monitoring.
Atazanavir and darunavir should be taken without IFN-containing options
ritonavir and other protease inhibitors are contra-
indicated with this combination. Elvitegravir/cobicistat Genotype 1, IFN-containing Option 1
should not be used with this regimen because of the
additional boosting effect (B1) • Patients infected with HCV genotype 1 can be treated
with a combination of weekly PegIFN-α, daily weight-
based ribavirin (1000 or 1200 mg in patients <75 kg or
≥75 kg, respectively), and daily sofosbuvir (400 mg) 12
weeks (A1)
Treatment of chronic hepatitis C, including patients without Comments: This combination has been evaluated in the
cirrhosis and patients with compensated (Child-Pugh A) NEUTRINO Phase III trial in treatment-naïve patients [25]. The
cirrhosis overall SVR rate was 89% (259/291), 92% (207/225) for subtype
1a and 82% (54/66) for subtype 1b. Patients with cirrhosis had a
In 2015 and onwards, treatment-naïve and treatment-experienced lower SVR rate than non-cirrhotic patients (80% vs. 92%, respec-
patients with compensated and decompensated liver disease will tively). Patients who failed on this regimen did not select HCV vari-
benefit from a broad choice of drug combinations. Indications will ants resistant to sofosbuvir. No Phase II data with this regimen has
depend on the HCV genotype/subtype, the severity of liver disease,
and/or the results of prior therapy. Notwithstanding the respective been presented in patients who failed prior PegIFN-a and ribavirin
costs of these options, IFN-free regimens are the best options when
available, because of their virological efficacy, ease of use and treatment. However, based on SVR rates in historical studies and
tolerability. The indications are the same in HCV-monoinfected the NEUTRINO trial, the US Food and Drug Administration pre-
and HIV-coinfected patients. However, treatment alterations or
dose adjustments may be needed in the latter due to drug-drug dicted that 78% of patients who failed prior PegIFN-a and ribavirin
interactions (see above, drug-drug interactions).
treatment would achieve an SVR with the triple combination of
PegIFN-a, ribavirin and sofosbuvir (although different models
yielded slightly different predictions) [26]. Similarly, there is no
data with this regimen in patients who failed prior PegIFN-a,
11
of the additional boosting effect.
Recommendations
Recommendations
• Indications for HCV treatment in HCV/HIV coinfected
• Numerous and complex drug-drug interactions are persons are identical to those in patients with HCV-
possible with the HCV DAAs, especially when they monoinfection (A1)
are used in IFN-free combinations. Strict rules should
thus be applied. As the data accumulate, guidance for • Notwithstanding the respective costs of these options,
contra-indications and dose adjustments can be found IFN-free regimens are the best options when available
in Tables 4A to 4F of these Recommendations and at in HCV-monoinfected and in HIV-coinfected patients
www.hep-druginteractions.org where they are regularly without cirrhosis or with compensated (Child-Pugh A) or
updated (B1) decompensated (Child-Pugh B or C) cirrhosis, because
of their virological efficacy, ease of use and tolerability
• The use of cobicistat-based regimens, efavirenz, (A1)
etravirine, nevirapine, ritonavir, and any HIV
protease inhibitor, boosted or not by ritonavir, is not • The same IFN-free treatment regimens can be used
recommended in HIV-infected patients receiving in HIV-coinfected patients as in patients without HIV
simeprevir (A1) infection, as the virological results of therapy are
identical (A1)
• The daily daclatasvir dose should be adjusted to 30
mg daily in HIV-infected patients receiving atazanavir/ For each genotype, the available options are described below, fol-
ritonavir and to 90 mg daily in those receiving efavirenz lowed by a summary of the data available for the given option,
(B2) and summarized in Tables 5 and 6.
• No drug-drug interaction has been reported between Treatment of HCV genotype 1 infection
sofosbuvir and antiretroviral drugs (A2)
Six treatment options are available in 2015 for patients infected
• The fixed-dose combination of sofosbuvir and ledipasvir with HCV genotype 1, including two IFN-containing regimens
can be used with all antiretrovirals. However, this and four IFN-free regimens. The combination of sofosbuvir and
regimen should not be used with the combination ribavirin should not be used in patients infected with HCV geno-
of tenofovir/emtricitabine with atazanavir/ritonavir, type 1. In settings where none of the proposed options is avail-
darunavir/ritonavir, lopinavir/ritonavir or elvitegravir/
cobicistat when possible, or used with caution with able, the double combination of PegIFN-a and ribavirin, or the
frequent renal monitoring (B1) triple combination of PegIFN-a, ribavirin and either telaprevir
• The combination of ritonavir-boosted paritaprevir, or boceprevir, remain acceptable for selected patients likely to
ombitasvir and dasabuvir should not be used with respond to these regimens until new DAAs become available
efavirenz, etravirine or nevirapine, and rilpivirine and affordable; see prior EASL Clinical Practice Guidelines [5,24].
should be used cautiously with repeat ECG monitoring.
Atazanavir and darunavir should be taken without IFN-containing options
ritonavir and other protease inhibitors are contra-
indicated with this combination. Elvitegravir/cobicistat Genotype 1, IFN-containing Option 1
should not be used with this regimen because of the
additional boosting effect (B1) • Patients infected with HCV genotype 1 can be treated
with a combination of weekly PegIFN-α, daily weight-
based ribavirin (1000 or 1200 mg in patients <75 kg or
≥75 kg, respectively), and daily sofosbuvir (400 mg) 12
weeks (A1)
Treatment of chronic hepatitis C, including patients without Comments: This combination has been evaluated in the
cirrhosis and patients with compensated (Child-Pugh A) NEUTRINO Phase III trial in treatment-naïve patients [25]. The
cirrhosis overall SVR rate was 89% (259/291), 92% (207/225) for subtype
1a and 82% (54/66) for subtype 1b. Patients with cirrhosis had a
In 2015 and onwards, treatment-naïve and treatment-experienced lower SVR rate than non-cirrhotic patients (80% vs. 92%, respec-
patients with compensated and decompensated liver disease will tively). Patients who failed on this regimen did not select HCV vari-
benefit from a broad choice of drug combinations. Indications will ants resistant to sofosbuvir. No Phase II data with this regimen has
depend on the HCV genotype/subtype, the severity of liver disease,
and/or the results of prior therapy. Notwithstanding the respective been presented in patients who failed prior PegIFN-a and ribavirin
costs of these options, IFN-free regimens are the best options when
available, because of their virological efficacy, ease of use and treatment. However, based on SVR rates in historical studies and
tolerability. The indications are the same in HCV-monoinfected the NEUTRINO trial, the US Food and Drug Administration pre-
and HIV-coinfected patients. However, treatment alterations or
dose adjustments may be needed in the latter due to drug-drug dicted that 78% of patients who failed prior PegIFN-a and ribavirin
interactions (see above, drug-drug interactions).
treatment would achieve an SVR with the triple combination of
PegIFN-a, ribavirin and sofosbuvir (although different models
yielded slightly different predictions) [26]. Similarly, there is no
data with this regimen in patients who failed prior PegIFN-a,
11
