Unique Populations

Patients With HIV/HCV Coinfection

Recommendations Related to HCV Medication Interactions With HIV Antiretroviral Medications

RECOMMENDED RATING
Antiretroviral drug switches, when needed, should be done in collaboration with the HIV practitioner. For HIV antiretroviral and HCV direct-acting antiviral combinations not addressed below, expert consultation is recommended. I, A

Daclatasvir when used in combination with other antivirals

Daclatasvir requires dose adjustment with ritonavir-boosted atazanavir (decrease to 30 mg/d), cobicistat-boosted atazanavir (decrease to 30 mg/d), elvitegravir/cobicistat (decrease to 30 mg/d), and efavirenz or etravirine (increase to 90 mg/d).
IIa, B

Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg)

Elbasvir/grazoprevir should be used with antiretroviral drugs with which it does not have clinically significant interactions: abacavir, emtricitabine, enfuvirtide, lamivudine, raltegravir, dolutegravir, rilpivirine, and tenofovir.
IIa, B

Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)a

Glecaprevir/pibrentasvir should be used with antiretroviral drugs with which it does not have clinically significant interactions: abacavir, emtricitabine, enfuvirtide, lamivudine, raltegravir, dolutegravir, rilpivirine, and tenofovir.
 

Given the limited data on the safety of elvitegravir/cobicistat with glecaprevir/pibrentasvir, monitoring for hepatic toxicity is recommended until additional safety data are available in HIV/HCV-coinfected patients.
IIa, B

Simeprevir used in combination with other antivirals

Simeprevir should be used with antiretroviral drugs with which it does not have clinically significant interactions: abacavir, emtricitabine, enfuvirtide, lamivudine, maraviroc, raltegravir, dolutegravir, rilpivirine, and tenofovir.
IIa, B

Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)

Sofosbuvir/velpatasvir can be used with most antiretrovirals, but not efavirenz, etravirine, or nevirapine. Because velpatasvir has the potential to increase tenofovir levels when given as tenofovir disoproxil fumarate, concomitant use mandates consideration of renal function and should be avoided in those with an eGFR <60 mL/min.
 

Due to limited experience with this drug combination, renal monitoring is recommended during the dosing period. Tenofovir alafenamide may be an alternative to tenofovir disoproxil fumarate during sofosbuvir/velpatasvir treatment for patients who take cobicistat or ritonavir as part of their antiretroviral therapy.
IIa, B

Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg)

Ledipasvir/sofosbuvir can be used with most antiretrovirals. Because this therapy increases tenofovir levels when given as tenofovir disoproxil fumarate, concomitant use mandates consideration of renal function and should be avoided in those with an eGFR <60 mL/min.
 

The absolute tenofovir levels are highest, and may exceed exposures for which there are established renal safety data, when tenofovir disoproxil fumarate is administered with ritonavir- or cobicistat-containing regimens. Due to lack of sufficient safety data with this drug combination, consideration should be given to changing the antiretroviral regimen. If the combination is used, renal monitoring is recommended during the dosing period. Tenofovir alafenamide may be an alternative to tenofovir disoproxil fumarate during ledipasvir/sofosbuvir treatment for patients who take cobicistat or ritonavir as part of their antiretroviral therapy.
IIa, C
For combinations expected to increase tenofovir levels, baseline and ongoing assessment for tenofovir nephrotoxicity is recommended. IIa, C

Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) with dasabuvir (600 mg) as part of an extended-release regimen or plus twice-daily dosed dasabuvir (250 mg)

Paritaprevir/ritonavir/ombitasvir plus dasabuvir should be used with antiretroviral drugs with which they do not have substantial interactions: atazanavir, dolutegravir, emtricitabine, enfuvirtide, lamivudine, raltegravir, and tenofovir.
 

The dose of ritonavir used for boosting atazanavir should be held when administered with paritaprevir/ritonavir/ombitasvir plus dasabuvir and then restored when HCV treatment is completed. Atazanavir (300 mg) should be administered at the same time as the fixed-dose HCV combination.
IIa, C

Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)/voxilaprevir (100 mg)

Sofosbuvir/velpatasvir/voxilaprevir should be used with antiretroviral drugs with which they do not have substantial interactions: dolutegravir, emtricitabine, enfuvirtide, lamivudine, rilpivirine, and raltegravir.
 

Given increases in voxilaprevir AUC with darunavir/ritonavir or elvitegravir/cobicistat coadministration and lack of clinical safety data, monitoring for hepatic toxicity is recommended until additional safety data are available in HIV/HCV-coinfected patients.
 

Because this therapy has the potential to increase tenofovir levels when given as tenofovir disoproxil fumarate, concomitant use mandates consideration of renal function and should be avoided in those with an eGFR <60 mL/min. In patients receiving sofosbuvir/velpatasvir/voxilaprevir and tenofovir disoproxil fumarate concomitantly, renal monitoring is recommended during the dosing period.
IIa, B
a This is a 3 tablet coformulation. Please refer to the prescribing information.

 

 

Regimens Not Recommended for Patients with HIV/HCV Coinfection

NOT RECOMMENDED RATING
Antiretroviral treatment interruption to allow HCV therapy is not recommended. III, A
Elbasvir/grazoprevir should not be used with cobicistat, efavirenz, etravirine, nevirapine, or any HIV protease inhibitor. III, B
Glecaprevir/pibrentasvir should not be used with atazanavir, ritonavir-containing antiretroviral regimens, efavirenz, or etravirine.   III, B
Sofosbuvir/velpatasvir should not be used with efavirenz, etravirine, or nevirapine. III, B
Sofosbuvir/velpatasvir/voxilaprevir should not be used with ritonavir-boosted atazanavir, efavirenz, etravirine, or nevirapine. III, B
Sofosbuvir-based regimens should not be used with tipranavir. III, B
Paritaprevir/ritonavir/ombitasvir plus dasabuvir should not be used with darunavir, efavirenz, ritonavir-boosted lopinavir, ritonavir-boosted tipranavir, etravirine, nevirapine, cobicistat, or rilpivirine. III, B
Paritaprevir/ritonavir/ombitasvir with or without dasabuvir should not be used in HIV/HCV-coinfected individuals who are not taking antiretroviral therapy. III, B
Ribavirin should not be used with didanosine, stavudine, or zidovudine. III, B
Simeprevir should not be used with cobicistat, efavirenz, etravirine, nevirapine, or any HIV protease inhibitor. III, B

Table 1.
Drug Interactions Between Direct-Acting Antivirals and Antiretroviral Drugs—Recommended Regimens

Green indicates coadministration is safe; yellow indicates a dose change or additional monitoring is warranted; and pink indicates the combination should be avoided.
 

 
Ledipasvir/ Sofosbuvir

(LDV/SOF)

Sofosbuvir/ Velpatasvir

(SOF/VEL)

Elbasvir/ Grazoprevir

(ELB/GRZ)

Glecaprevir/ Pibrentasvir

(GLE/PIB)

Sofosbuvir/ Velpatasvir/ Voxilaprevir

(SOF/VEL/VOX)

Ritonavir-
boosted
atazanavir
​(ATZ)
 LDV
 ATZa
 VEL
 ATZa
 ELB
 GRZ
 ATZ
 GLE
 PIB
 ATZ
 VOX
 ATZ
Ritonavir-
boosted
darunavir
​(DRV)
 LDV
 DRVa
 VEL
 DRVa
 ELB
 GRZ
 DRV
 GLE
 PIB
 DRV
 VOX
 DRV
Ritonavir-
boosted
lopinavir
​(LPV)
NDa  VEL
 LPVa
 ELB
 GRZ
 LPV
 GLE
 PIB
 LPV
ND
Ritonavir-
boosted
tipranavir
​(TPV/r)
ND ND ND ND ND
Efavirenz
​(EFV)
 LDV
 EFVa
 VEL
 EFV
 ELB
 GRZ
 EFV
ND ND
Rilpivirine
​(RPV)
 LDV
 RPV
 VEL
 RPV
 ELB
 GRZ
 RPV
 GLE
 PIB
 RPV

 VOX
 RPV
Etravirine
​(ETV)
ND ND ND ND ND
Raltegravir
​(RAL)
 LDV
 RAL

 VEL
 RAL

 ELB
 GRZ
 RAL
 GLE
 PIB
 RAL
ND
Cobicistat-
boosted
elvitegravir
​(COB)
 LDV
 COBa
 VEL
 COBa
 ELB
 GRZ
 COB
 GLE
 PIB
 COB
 VOX
 COBa
Dolutegravir
​(DTG)
 LDV
 DTG
 VEL
 DTG
 ELB
 GRZ
 DTG
 GLE
 PIB
 DTG
ND
Tenofovir
Alafenamide (TAF)/
Emtricitabine (FTC)/
Bictegravir (BIC)
 LDV
 BIC
ND ND ND  VOX
 BIC
Maraviroc
​(MVC)
ND ND ND ND ND
Tenofovir
​(TFV)
disoproxil
fumarate
 LDV
 TFVc
 VEL
 TFVb
 ELB
 GRZ
 TFV
  TFV  TFVb
Tenofovir
​(TFV)
alafenamide
 LDV
 TFVd
 VEL
 TFVd
ND  TFV  TFVb
ND, No data
a Caution only with tenofovir disoproxil fumarate
b Increase in tenofovir depends on which additional concomitant antiretroviral agents are administered.
c Avoid tenofovir disoproxil fumarate in patients with an eGFR <60 mL/min; tenofovir concentrations may exceed those with established renal safety data in individuals on ritonavir- or cobicistat-containing regimens.
d Studied as part of fixed-dose combinations with ledipasvir/sofosbuvir or sofosbuvir/velpatasvir plus TAF, emtricitabine, elvitegravir, and cobicistat.

 

Table 2.
Drug Interactions Between Direct-Acting Antivirals and Antiretroviral Drugs—Alternative Regimens

Green indicates coadministration is safe; yellow indicates a dose change or additional monitoring is warranted; and pink indicates the combination should be avoided.
 

 
Simeprevir/ Sofosbuvir

(SMV/SOF)

Daclatasvir/ Sofosbuvir

(DCV/SOF)

Paritaprevir/ Ritonavir/ Ombitasvir + Dasabuvir

(PrOD)

Paritaprevir/ Ritonavir/ Ombitasvir

(PrO)

Ritonavir-
boosted
atazanavir
(ATZ)
ND  DCVa  PRV
 ATZ
 PRV
 ATZ
Ritonavir-
boosted
darunavir
(DRV)
 SMV
 DRV
 DCV
 DRV
 PRV
 DRV
 PRV
 DRV
Ritonavir-
boosted
lopinavir
(LPV)
ND  DCV
 LPV
 PRV
 LPV
 PRV
 LPV
Ritonavir-
boosted
tipranavir
(TPV/r)
ND ND ND ND
Efavirenz
(EFV)
 SMV
 EFV
 DCVb NPDc ND
Rilpivirine
(RPV)
 SMV
 RPV
ND  PRV
 RPV
ND
Etravirine
(ETV)
ND  DCVb ND ND
Raltegravir
(RAL)
 SMV
 RAL
ND  PrOD
 RAL
 PrO
 RAL
Cobicistat-
boosted
elvitegravir
(COB)
ND  DCVa ND ND
Dolutegravir
(DTG)
 SMV
 DTG
 DCV
 DTG
 PRV
 DTG
ND
Tenofovir
Alafenamide (TAF)/
Emtricitabine (FTC)/
Bictegravir (BIC)
ND ND ND ND
Maraviroc
(MVC)
ND ND ND ND
Tenofovir
(TFV)
disoproxil
fumarate
 SMV
 TFV
 DCV
 TFV
 PrOD
 TFV
 PrO
 TFV
Tenofovir
(TFV)
alafenamide
ND ND ND ND
ND, No data
a Daclatasvir dose should be reduced to 30 mg.
b Daclatasvir dose should be increased to 90 mg.

 

Treatment Recommendations for Patients With HIV/HCV Coinfection 

RECOMMENDED RATING

HIV/HCV-coinfected persons should be treated and retreated the same as persons without HIV infection, after recognizing and managing interactions with antiretroviral medications (see Initial Treatment of HCV Infection and Retreatment of Persons in Whom Prior Therapy Has Failed).

I, B

Daily daclatasvir (refer to information above for dose) plus sofosbuvir (400 mg), with or without ribavirin, is a recommended regimen when antiretroviral regimen changes cannot be made to accommodate alternative HCV direct-acting antivirals. Refer to Initial Treatment of HCV Infection and Retreatment of Persons in Whom Prior Therapy Has Failed sections for treatment duration.

I, B

 

Regimens Not Recommended for Patients With HIV/HCV Coinfection

NOT RECOMMENDED RATING
Ledipasvir/sofosbuvir for 8 weeks is not recommended, regardless of baseline HCV RNA level. IIb, C

 

Last update: 
May 24, 2018

Patients With Decompensated Cirrhosis

Recommended for All Patients With HCV Infection Who Have Decompensated Cirrhosis 

RECOMMENDED RATING
Patients with HCV infection who have decompensated cirrhosis—moderate or severe hepatic impairment, ie, Child-Turcotte-Pugh (CTP) class B or class C—should be referred to a medical practitioner with expertise in that condition, ideally in a liver transplant center. I, C

 

Decompensated Cirrhosis Genotype 1, 4, 5, or 6 Infection

Recommended regimens listed by evidence level and alphabetically for:

Patients With Decompensated Cirrhosisa Who Have Genotype 1, 4, 5, or 6 Infection and Are Ribavirin Eligible

RECOMMENDED DURATION RATING
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increase as tolerated)  12 weeks I, Ab
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) with weight-based ribavirinc 12 weeks I, Ad
Genotype 1 or 4 infection only: Daily daclatasvir (60 mg)e plus sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increase as tolerated)  12 weeks I, B
a Includes CTP class B and class C patients who may or may not be candidates for liver transplantation, including those with hepatocellular carcinoma.
​b Only available data for genotypes 5 and 6 are in a small number of patients with compensated cirrhosis.
​c Low initial dose of ribavirin (600 mg) is recommended for patients with CTP class C cirrhosis; increase as tolerated.
​d Only available data for genotype 6 are in patients with compensated cirrhosis.
e The dose of daclatasvir may need to be increased or decreased when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively. Please refer to the prescribing information for daclatasvir.

 

Recommended regimens listed by evidence level and alphabetically for:

Patients With Decompensated Cirrhosisa Who Have Genotype 1, 4, 5, or 6 Infection and Are Ribavirin Ineligible

RECOMMENDED DURATION RATING
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) 24 weeks I, Ab
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 24 weeks I, Ac
Genotype 1 or 4 infection only: Daily daclatasvir (60 mg)d plus sofosbuvir (400 mg)  24 weeks II, C
a Includes CTP class B and class C patients who may or may not be candidates for liver transplantation, including those with hepatocellular carcinoma.
​b Only available data for genotypes 5 and 6 are in a small number of patients with compensated cirrhosis.
​c Only available data for genotype 6 are in patients with compensated cirrhosis.
d The dose of daclatasvir may need to be increased or decreased when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively. Please refer to the prescribing information for daclatasvir.

 

Recommended regimens listed by evidence level and alphabetically for:

Patients With Decompensated Cirrhosisa and Genotype 1, 4, 5, or 6 Infection in Whom Prior Sofosbuvir- or NS5A-Based Treatment Failed

RECOMMENDED DURATION RATING
Prior sofosbuvir-based treatment failure only: Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg; increase as tolerated)  24 weeks II, Cb
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) with weight-based ribavirinc 24 weeks II, Cd

a Includes CTP class B and class C patients who may or may not be candidates for liver transplantation, including those with hepatocellular carcinoma.
b Only available data for genotype 6 are in patients with compensated cirrhosis.
c Low initial dose of ribavirin (600 mg) is recommended for patients with CTP class C cirrhosis.
d Only available data for genotypes 5 and 6 are in a small number of patients with compensated cirrhosis.

 

Decompensated Cirrhosis Genotype 2 or 3 Infection

Recommended Regimens listed by evidence level and alphabetically for:

Patients With Decompensated Cirrhosisa Who Have Genotype 2 or 3 Infection and Are Ribavirin Eligible

RECOMMENDED DURATION RATING
Daily fixed-dose combination sofosbuvir (400 mg)/velpatasvir (100 mg) with weight-based ribavirin 12 weeks I, A
Daily daclatasvir (60 mg)b plus sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increase as tolerated) 12 weeks II, B
a Includes CTP class B and class C patients who may or may not be candidates for liver transplantation, including those with hepatocellular carcinoma.
b The dose of daclatasvir may need to be increased or decreased when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively. Please refer to the prescribing information for daclatasvir.

 

Recommended regimens listed by evidence level and alphabetically for:

Patients With Decompensated Cirrhosisa Who Have Genotype 2 or 3 Infection and Are Ribavirin Ineligible

RECOMMENDED DURATION RATING
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 24 weeks I, A
Daily daclatasvir (60 mg)b plus sofosbuvir (400 mg) 24 weeks II, C

a Includes CTP class B and class C patients who may or may not be candidates for liver transplantation, including those with hepatocellular carcinoma.
b The dose of daclatasvir may need to be increased or decreased when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively. Please refer to the prescribing information for daclatasvir.

 

 

Recommended regimens listed by evidence level and alphabetically for:

Patients With Decompensated Cirrhosisa and Genotype 2 or 3 Infection in Whom Prior Sofosbuvir- or NS5A-Based Treatment Failed

RECOMMENDED DURATION RATING
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) with weight-based ribavirinb 24 weeks II, C

a Includes CTP class B and class C patients who may or may not be candidates for liver transplantation, including those with hepatocellular carcinoma.
b Low initial dose of ribavirin (600 mg) is recommended for patients with CTP class C.

 

 

Regimens not recommended for:

Patients With Decompensated Cirrhosis (Moderate or Severe Hepatic Impairment; Child-Turcotte-Pugh Class B or C)

NOT RECOMMENDED RATING
Paritaprevir-based regimens III, B
Simeprevir-based regimens III, B
Elbasvir/grazoprevir-based regimens III, C
Glecaprevir/pibrentasvir III, C
Sofosbuvir/velpatasvir/voxilaprevir III, C

 

Last update: 
September 21, 2017

Patients Who Develop Recurrent HCV Infection Post Liver Transplantation

Post Liver Transplantation: Genotype 1, 4, 5, or 6 Infection​

Recommended regimens listed by evidence level and alphabetically for:

Treatment-Naive and -Experienced Patients With Genotype 1, 4, 5, or 6 Infection in the Allograft Without Cirrhosis

RECOMMENDED DURATION RATING
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)a 12 weeks I, A
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with weight-based ribavirin 12 weeks I, A
a This is a 3-tablet coformulation. Please refer to the prescribing information.

 

Recommended regimen for:

Treatment-Naive and -Experienced Patients With Genotype 1, 4, 5, or 6 Infection in the Allograft With Compensated Cirrhosis 

RECOMMENDED DURATION RATING
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with weight-based ribavirin for 12 weeks 12 weeks I, A

 

 

Alternative regimens listed by evidence level and alphabetically for:

Treatment-Naive and -Experienced Patients With Genotype 1, 4, 5, or 6 Infection in the Allograft, With or Without Compensated Cirrhosis 

ALTERNATIVE DURATION RATING
Daily daclatasvir (60 mg)a plus sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increase as tolerated) 12 weeks I, B
Genotype 1 or 4 infection only: Daily simeprevir (150 mg) plus sofosbuvir (400 mg) with or without weight-based ribavirin 12 weeks I, B
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b 12 weeks IIa, C
a The dose of daclatasvir may need to be increased or decreased when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively. Please refer to the prescribing information and the section on HIV/HCV coinfection for patients on antiretroviral therapy.
b This is a 3-tablet coformulation. Please refer to the prescribing information.

 

Recommended regimen for:

Treatment-Naive and -Experienced Patients With Genotype 1, 4, 5, or 6 Infection in the Allograft and Decompensated Cirrhosisa 

RECOMMENDED DURATION RATING
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increase as tolerated) 12 weeks I, B
a Includes CTP class B and class C patients.

 

 

Post Liver Transplantation: Genotype 2 or 3 Infection

Recommended regimens listed by evidence level and alphabetically for:

Treatment-Naive and -Experienced Patients With Genotype 2 or 3 Infection in the Allograft Without Cirrhosis

RECOMMENDED DURATION RATING
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)a 12 weeks I, A
Daily daclatasvir (60 mg)b plus sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increase as tolerated) 12 weeks II, A
a This is a 3-tablet coformulation. Please refer to the prescribing information.
b The dose of daclatasvir may need to be increased or decreased when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively. Please refer to the prescribing information and the section on HIV/HCV coinfection for patients on antiretroviral therapy.

 

Recommended and alternative regimens listed by evidence level and alphabetically for:

Treatment-Naive and -Experienced Patients With Genotype 2 or 3 Infection in the Allograft With Compensated Cirrhosis 

RECOMMENDED DURATION RATING
Daily daclatasvir (60 mg)a plus sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increase as tolerated) 12 weeks II, A
ALTERNATIVE DURATION RATING
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b 12 weeks II, C
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) with weight-based ribavirin 12 weeks II, C
a The dose of daclatasvir may need to be increased or decreased when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively. Please refer to the prescribing information and the section on HIV/HCV coinfection for patients on antiretroviral therapy.
b This is a 3-tablet coformulation. Please refer to the prescribing information.

 

Recommended regimens listed by evidence level and alphabetically for:

Treatment-Naive and -Experienced Patients With Genotype 2 or 3 Infection in the Allograft and Decompensated Cirrhosisa 

RECOMMENDED DURATION RATING
Daily daclatasvir (60 mg)b plus sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increase as tolerated) 12 weeks II, A
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) with weight-based ribavirin 12 weeks II, C
a Includes CTP class B and class C patients.
b The dose of daclatasvir may need to be increased or decreased when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively. Please refer to the prescribing information and the section on HIV/HCV coinfection for patients on antiretroviral therapy.

 

 

Table. DAA Interactions With Calcineurin Inhibitors
 

 

Cyclosporine (CSA)

Tacrolimus (TAC)

Sofosbuvir (SOF) 4.5-fold ↑ in SOF AUC, but GS-331007 metabolite unchanged; no a priori dose adjustment No interaction observed; no a priori dose adjustment
Ledipasvir No data; no a priori dose adjustment No data; no a priori dose adjustment

Paritaprevir / ritonavir / ombitasvir + dasabuvir (PrOD)

5.8-fold ↑ in CSA AUC; modeling suggest using 1/5 of CSA dose during PrOD treatment, monitor CSA levels and titrate CSA dose as needed 57-fold ↑ in TAC AUC; modeling suggests TAC 0.5 mg every 7 days during PrOD treatment, monitor TAC levels and titrate TAC dose as needed
Elbasvir / grazoprevir (EBR/GZR) 15-fold ↑ in GZR AUC and 2-fold ↑ in EBR AUC; combination is not recommended 43% ↑ in TAC; no a priori dose adjustment
Velpatasvir No interaction observed; no a priori dose adjustment No data; no a priori dose adjustment
Glecaprevir / pibrentasvir (GLE/PIB) 5-fold ↑ in GLE AUC with higher doses (400 mg) of CSA; not recommended in patients requiring stable CSA doses >100 mg/day 1.45-fold ↑ in TAC AUC; no a priori dose  adjustment, monitor TAC levels and titrate TAC dose as needed
Sofosbuvir / velpatasvir / voxilaprevir (SOF/VEL/VOX) 9.4-fold ↑ in VOX AUC; combination is not recommended No data; no a priori dose adjustment
AUC=area under the curve

 

 

Last update: 
September 21, 2017

Patients with Renal Impairment

Recommendations for Patients With CKD Stagea 1, 2, or 3

RECOMMENDED RATING
No dose adjustment is required when using:
  • Daclatasvir (60 mg)b
  • Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg)
  • Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)c
  • Fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg)
  • Fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)
  • Simeprevir (150 mg)
  • Fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)/
    voxilaprevir (100 mg)
  • Sofosbuvir (400 mg) 
I, A
a Chronic kidney disease (CKD) stages: 1 = normal (eGFR >90 mL/min); 2 = mild CKD (eGFR 60-89 mL/min); 3 = moderate CKD (eGFR 30-59 mL/min); 4 = severe CKD (eGFR 15-29 mL/min); 5 = end-stage CKD (eGFR <15 mL/min)
b Refer to the prescribing information and the section on HIV/HCV coinfection for patients on antiretroviral therapy.
c This is a 3-tablet coformulation. Please refer to the prescribing information.

 

Recommended regimens listed by evidence level and alphabetically for:

Patients With CKD Stagea 4 or 5 (eGFR <30 mL/min or End-Stage Renal Disease)

RECOMMENDED GENOTYPE DURATION RATING
Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) 1a, 1b, 4 12 weeks I, B
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b 1, 2, 3, 4, 5, 6 8 to 16 weeksc I, Bc
a Chronic kidney disease (CKD) stages: 1 = normal (eGFR >90 mL/min); 2 = mild CKD (eGFR 60-89 mL/min); 3 = moderate CKD (eGFR 30-59 ml/min); 4 = severe CKD (eGFR 15-29 mL/min); 5 = end-stage CKD (eGFR <15 mL/min)
b This is a 3-tablet coformulation. Please refer to the prescribing information.
c Patients in this group should be treated as would patients without CKD. Duration of glecaprevir/pibrentasvir should be based on presence of cirrhosis and prior treatment experience (please refer to appropriate section). As such, strength of rating may be lower for certain subgroups.

 

Last update: 
September 21, 2017

Kidney Transplant Patients

Genotypes 1 and 4

Recommended regimens listed by evidence level and alphabetically for:

Treatment-Naive and -Experienced Kidney Transplant Patients With Genotype 1 or 4 Infection, With or Without Compensated Cirrhosis

RECOMMENDED DURATION RATING

Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b

12 weeks I, Ac
IIa, Cd
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) 12 weeks I, A
a For decompensated cirrhosis, please refer to the appropriate section.
b This is a 3-tablet coformulation. Please refer to the prescribing information.
c Evidence for patients without cirrhosis
d Evidence for patients with compensated cirrhosis

 

Genotypes 2, 3, 5, and 6

Recommended and alternative regimens for:

Treatment-Naive and -Experienced Kidney Transplant Patients With Genotype 2, 3, 5, or 6 Infection, With or Without Compensated Cirrhosis

RECOMMENDED DURATION RATING
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b 12 weeks I, Ac
IIa, Cd
ALTERNATIVE DURATION RATING
Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) plus low initial dose of ribavirin (600 mg; increase as tolerated) 12 weeks II, A
a For decompensated cirrhosis, please refer to the appropriate section.
b This is a 3-tablet coformulation. Please refer to the prescribing information.
c Genotypes 2, 3, and 6
d Genotype 5
Last update: 
September 21, 2017

Management of Acute HCV Infection

Diagnosis of Acute HCV

Recommended Testing for Diagnosing Acute HCV Infection

RECOMMENDED RATING
HCV antibody and HCV RNA testing are recommended when acute HCV infection is suspected due to exposure, clinical presentation, or elevated aminotransferase levels (see Testing Algorithm figure). I, C

 

Pharmacologic Prophylaxis

Pharmacologic Prophylaxis Not Recommended

NOT RECOMMENDED RATING
Pre-exposure or post-exposure prophylaxis with antiviral therapy is not recommended. III, C
 

 

Medical Management and Monitoring of Acute HCV Infection

Recommendations for Medical Management and Monitoring of Acute HCV Infection

RECOMMENDED RATING
Regular laboratory monitoring is recommended in the setting of acute HCV infection. Monitoring HCV RNA (eg, every 4 to 8 weeks) for 6 to 12 months is also recommended to determine spontaneous clearance versus persistence of HCV infection. I, B
Counseling is recommended for patients with acute HCV infection to avoid hepatotoxic insults, including hepatotoxic drugs (eg, acetaminophen) and alcohol consumption, and to reduce the risk of HCV transmission to others. I, C
Referral to an addiction medicine specialist is recommended for patients with acute HCV infection related to substance use. I, B

 

Antiviral Therapy

Recommended Treatment for Patients With Acute HCV Infection

RECOMMENDED RATING
If the clinician and patient decide that a delay in treatment initiation is acceptable, monitoring for spontaneous clearance is recommended for a minimum of 6 months. When the decision is made to initiate treatment after 6 months, treating as described for chronic hepatitis C is recommended (see Initial Treatment of HCV Infection). IIa, C
If a decision is made to initiate treatment during the acute infection period, monitoring HCV RNA for at least 12 to 16 weeks before starting treatment is recommended to allow time for possible spontaneous clearance. IIa, C

 

Recommended Regimens for Patients With Acute HCV Infection

RECOMMENDED RATING
Owing to high efficacy and safety, the same regimens that are recommended for chronic HCV infection are recommended for acute infection. IIa, C

 

When Antiviral Therapy Is Not Recommended

NOT RECOMMENDED RATING
For patients in whom HCV infection spontaneously clears, antiviral treatment is not recommended. III, B

 

Last update: 
September 21, 2017

HCV in Pregnancy

Testing

Recommendation for Universal Hepatitis C Screening in Pregnancy

RECOMMENDED RATING
All pregnant women should be tested for HCV infection (see Recommendations for Initial HCV Testing and Follow-Up), ideally at the initiation of prenatal care. IIb, C

 

Whom to Treat

Recommendation Regarding HCV Treatment and Pregnancy

RECOMMENDED RATING
For women of reproductive age with known HCV infection, antiviral therapy is recommended before considering pregnancy, whenever practical and feasible, to reduce the risk of HCV transmission to future offspring. I, B

 

Not Recommended Regarding HCV Treatment and Pregnancy

NOT RECOMMENDED RATING
Treatment during pregnancy is not recommended due to the lack of safety and efficacy data. IIb, C

 

Monitoring During Pregnancy

Recommendations for Monitoring HCV-Infected Women During Pregnancy

RECOMMENDED RATING
HCV RNA and routine liver function tests are recommended at initiation of prenatal care for HCV-antibody–positive pregnant women to assess the risk of mother-to-child transmission (MTCT) and degree of liver disease.  I, B
All pregnant women with HCV infection should receive prenatal and intrapartum care that is appropriate for their individual obstetric risk(s) as there is no currently known intervention to reduce MTCT. I, B
In HCV-infected pregnant women with pruritus or jaundice, there should be a high index of suspicion for intrahepatic cholestasis of pregnancy (ICP) with subsequent assessment of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum bile acids. I, B
HCV-infected women with cirrhosis should be counseled about the increased risk of adverse maternal and perinatal outcomes. Antenatal and perinatal care should be coordinated with a maternal-fetal medicine (ie, high-risk pregnancy) obstetrician. I, B

 

Postpartum Issues

Recommendations Regarding Breastfeeding and Postpartum Care for HCV-Infected Women

RECOMMENDED RATING
Breastfeeding is not contraindicated in women with HCV infection, except when the mother has cracked, damaged, or bleeding nipples, or in the context of HIV coinfection. I, B
Women with HCV infection should have their HCV RNA reevaluated after delivery to assess for spontaneous clearance. I, B
Last update: 
May 24, 2018

HCV in Children

Testing

Recommendations for HCV Testing of Perinatally Exposed Children and Siblings of HCV-Infected Children

RECOMMENDED RATING
All children born to HCV-infected women should be tested for HCV infection. Testing is recommended using an antibody-based test at or after 18 months of age. I, A
Testing with an HCV-RNA assay can be considered in the first year of life, but the optimal timing of such a test is unknown. IIa, C
Repetitive testing by HCV RNA is not recommended. III, A
Children who are anti-HCV positive after 18 months of age should be tested with an HCV-RNA assay after age 3 to confirm chronic hepatitis C infection. I, A
The siblings of children with vertically-acquired chronic HCV should be tested for HCV infection, if born from the same mother. I, C

 

Transmission and Prevention

Recommendations for Counseling Parents Regarding Transmission and Prevention in HCV-Infected Children

RECOMMENDED RATING
Parents should be informed that hepatitis C is not transmitted by casual contact and, as such, HCV-infected children do not pose a risk to other children and can participate in school, sports, and athletic activities, and engage in all other regular childhood activities without restrictions. I, B
Parents should be informed that universal precautions should be followed at school and in the home of children with HCV infection. Educate families and children about the risk and routes of HCV transmission, and the techniques for avoiding blood exposure, such as avoiding the sharing of toothbrushes, razors, and nail clippers, and the use of gloves and dilute bleach to clean up blood. I, B

 

 

Monitoring and Medical Management

Recommendations for Monitoring and Medical Management of HCV-Infected Children

RECOMMENDED RATING
Routine liver biochemistries at initial diagnosis and at least annually thereafter are recommended to assess for disease progression. I, C
Appropriate vaccinations are recommended for HCV-infected children not immune to hepatitis B virus and/or hepatitis A virus to prevent these infections. I, C
Disease severity assessment via routine laboratory testing and physical examination, as well as use of evolving noninvasive modalities (ie, elastography, imaging, or serum fibrosis markers) is recommended for all children with chronic HCV. I, B
Children with cirrhosis should undergo hepatocellular carcinoma (HCC) surveillance and endoscopic surveillance for varices per standard recommendations. I, B
Hepatotoxic drugs should be used with caution in children with chronic HCV after assessment of potential risk versus benefit of treatment. Use of corticosteroids, cytotoxic chemotherapy, or therapeutic doses of acetaminophen are not contraindicated in children with chronic HCV. II, C
Solid organ transplantation and bone marrow transplantation are not contraindicated in children with chronic HCV. II, C
Anticipatory guidance about the potential risks of ethanol for progression of liver disease is recommended for children with HCV and their families. Abstinence from alcohol and interventions to facilitate cessation of alcohol consumption, when appropriate, are advised for all persons with HCV infection. I, C

 

 

Treatment

Recommendations for Whom and When to Treat Among HCV-Infected Children

RECOMMENDED RATING
If direct-acting antiviral (DAA) regimens are available for a child’s age group, treatment is recommended for all HCV-infected children older than 3 years as they will benefit from antiviral therapy, independent of disease severity. I, B
Treatment of children aged 3 to 11 years with chronic hepatitis C should be deferred until interferon-free regimens are available. II, C
The presence of extrahepatic manifestations—such as cryoglobulinemia, rashes, and glomerulonephritis—as well as advanced fibrosis should lead to early antiviral therapy to minimize future morbidity and mortality. I, C

 

Recommended regimens listed by evidence level and alphabetically for:

Adolescents ≥12 Years Old or Weighing ≥35 kg, Without Cirrhosis or With Compensated Cirrhosis

RECOMMENDED DURATION RATING
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for patients with genotype 1 who are treatment-naive without cirrhosis or with compensated cirrhosisa, or treatment-experiencedb without cirrhosis 12 weeks I, B
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for patients with genotype 1 who are treatment-experiencedb with compensated cirrhosisa 24 weeks I, B
Daily sofosbuvir (400 mg) plus weight-based ribavirinc for patients with genotype 2 who are treatment-naive or treatment-experiencedb without cirrhosis or with compensated cirrhosisa 12 weeks I, B
Daily sofosbuvir (400 mg) plus weight-based ribavirinc for patients with genotype 3 who are treatment-naive or treatment-experiencedb without cirrhosis or with compensated cirrhosisa 24 weeks I, B
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for patients with genotype 4, 5, or 6 who are treatment-naive or treatment-experiencedb without cirrhosis or with compensated cirrhosisa 12 weeks I, B
a Child-Pugh A
b Patients who have failed an interferon-based regimen, with or without ribavirin
c See ribavirin dosing table for recommended weight-based dosages.

 

Last update: 
May 24, 2018

Key Populations: Identification and Management of HCV in People Who Inject Drugs

Recommendations for Screening and Treatment of HCV Infection in People Who Inject Drugs (PWID)

RECOMMENDED RATING
Annual HCV testing is recommended for PWID with no prior testing, or past negative testing and subsequent injection drug use. Depending on the level of risk, more frequent testing may be indicated. IIa, C
Substance use disorder treatment programs and needle/syringe exchange programs should offer routine, opt-out HCV-antibody testing with reflexive or immediate confirmatory HCV-RNA testing and linkage to care for those who are infected. IIa, C
PWID should be counseled about measures to reduce the risk of HCV transmission to others. I, C
PWID should be offered linkage to harm reduction services when available, including needle/syringe service programs and substance use disorder treatment programs. I, B
Active or recent drug use or a concern for reinfection is not a contraindication to HCV treatment. IIa, B

 

Recommendation for Testing for Reinfection in People Who Inject Drugs (PWID) 

RECOMMENDED RATING
At least annual HCV-RNA testing is recommended for PWID with recent injection drug use after they have spontaneously cleared HCV infection or have been successfully treated. IIa, C

 

Last update: 
May 24, 2018

HCV in Key Populations: Men Who Have Sex With Men

Testing

Recommendations for Testing and Prevention of HCV Infection in Men Who Have Sex With Men (MSM)

RECOMMENDED RATING
Annual HCV testing is recommended for sexually active HIV-infected adolescent and adult MSM. Depending on the presence of high-risk sexual or drug use practices, more frequent testing may be warranted. IIa, C
HCV testing at HIV pre-exposure prophylaxis (PrEP) initiation and at least annually thereafter (while on PrEP) is recommended in HIV-uninfected MSM. Depending on sexual or drug use risk practices, more frequent testing may be warranted. IIa, C
All MSM should be counseled about the risk of sexual HCV transmission with high-risk sexual and drug use practices, and educated about measures to prevent HCV infection or transmission. IIa, C

 

Treatment

Recommendation on Treatment of HCV in Men Who Have Sex With Men (MSM)

RECOMMENDED RATING
Antiviral treatment for HCV-infected MSM should be coupled with ongoing counseling about the risk of HCV reinfection, and education about methods to reduce HCV reinfection risk after cure. I, B

 

Testing for HCV Reinfection

Recommendation on Prevention of HCV Reinfection in Men Who Have Sex With Men (MSM)

RECOMMENDED RATING
At least annual (and risk-based, if indicated) HCV testing with HCV RNA is recommended for sexually active MSM after successfully treated or spontaneously cleared HCV infection. IIa, C

 

Last update: 
May 24, 2018
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