HIV and HCV Update for the Pharmacist

Report
HIV and HCV Update for the
Pharmacist – June 2014
John J. Faragon, PharmD, BCPS, AAHIV-P
Regional Pharmacy Director, NY/NJ AETC
Pharmacist, Albany Medical Center
Objectives
• Discuss recent guidelines changes for HIV
infection
• Using patient cases, discuss the role of
sofosbuvir and simeprevir in HIV/HCV coinfection
• Review consensus guidelines for
managing HIV/HCV coinfection
2
DHHS Guidelines Update 2014: Recommended
Regimens in ARV Naives Regardless of Baseline
CD4 and Viral Load
NNRTI – Based Regimen
Efavirenz/tenofovir/emtricitabine (AI)
PI – Based Regimens:
Atazanavir/ritonavir + tenofovir/emtrictiabine (AI)
Darunavir/ritonavir + tenofovir/emtricitabine (AI)
INSTI – Based Regimens:
Dolutegravir plus abacavir/lamivudine – ONLY if patient HLA-B*5701 negative (AI)
Dolutegravir plus tenofovir/emtricitabine (AI)
Elvitegravir/cobicistat/tenofovir/emtricitabine – ONLY if pre-ART CrCl >70ml/min (AI)
Raltegravir plus tenofovir/emtricitabine (AI)
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.
Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed 5/2/14
DHHS Guidelines Initial
Recommended Regimens - 2014
Atripla
1/day
Reyataz/Norvir/Truvada
3/day
Prezista/Norvir/Truvada
3/day
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.
Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed 5/2/14.
DHHS Guidelines Initial
Recommended Regimens - 2014
Isentress (BID)/Truvada
3/day
Tivicay/Truvada OR Epzicom
OR
2/day
Stribild
1/day
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.
Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed 5/2/14.
DHHS Guidelines Update 2014: Recommended
Regimens, ARV Naives, ONLY if Pre ART Viral
Load <100,000 copies/ml
NNRTI – Based Regimen
Efavirenz + abacavir/lamivudine – ONLY if patient HLA-B*5701 negative (AI)
Rilpivirine/tenofovir/emtricitabine – ONLY if patient has CD4 count>200 cells/mm3 (AI)
PI – Based Regimens:
Atazanavir/ritonavir + abacavir/lamivudine (AI) – ONLY if patient is HLA-B*5701 negative
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.
Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed 5/2/14
DHHS Guidelines Update 2014
Alternative Regimens in ARV Naives
PI – Based Regimen
Darunavir/ritonavir + abacavir/lamivudine – ONLY for patients who are HLA-B*5701
negative (BII)
Lopinavir/ritonavir (once or twice daily) plus abacavir/lamivudine – ONLY for
patients who are HLA-B*5701 negative (BI)
Lopinavir/ritonavir (once or twice daily) plus tenofovir/emtricitabine (BI)
INSTI – Based Regimens:
Raltegravir + abacavir/lamivudine – ONLY for patients who are HLA-B*5701 negative
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.
Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed 5/2/14
Preferred NRTI Backbones in Pregnancy –
DHHS Perinatal Guidelines, March 2014
Preferred NRTI Backbones
Abacavir/lamivudine
Available as fixed dose combination, once
daily dosing. Do NOT use in patients
testing positive for HLAB*5701
Tenofovir/emtricitabine or lamivudine
Available as fixed dose combination, once
daily dosing. Tenofovir may cause renal
impairment
Zidovudine/lamivudine
Available as fixed dose combination.
Most experience in pregnancy to date,
but twice daily adminstration, and
potential for hematologic toxicity
Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs
in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Available at
http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed 5/2/14
Preferred PI, NNRTI Regimens in Pregnancy –
DHHS Perinatal Guidelines, March 2014
Preferred PI Regimens
Atazanavir/ritonavir + preferred dual
NRTI backbone
Once daily administration
Lopinavir/ritonavir + preferred dual NRTI
backbone
Twice daily administration. Once daily
dosing not recommended in pregnancy.
May need to increase dosage in 3rd
trimester
Preferred NNRTI Regimens
Efavirenz + preferred dual NRTI backbone Teratogenicity in primates.
initiated AFTER first 8 weeks of pregnancy
Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral
Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States.
Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed 5/2/14
Current Medications for HCV
 Older Medications
 Pegylated Interferon – PegIntron or Pegasys
 Ribavirin
 Older Direct Acting Antivirals
 Boceprevir (Victrelis)
 Telaprevir (Incivek)
 New Direct Acting Antivirals
 Simeprevir (Olysio)
 Sofosbuvir (Sovaldi)
Challenges with Older DAA
 Telaprevir (Incivek)
 Rash – Black Box Warning
 Anemia – Worse than Pegylated interferon +
Ribavirin alone
 Needs interferon and ribavirin – brings all ADRs
with it too
 Anorectal adverse events challenging
 Only for Genotype 1 – ie not pangenotypic
 Response guided therapy/stopping rules
 Drug Interactions complex, especially when
treating co-infection
 Large pull burden (6/day), TID, now BID
frequency
Challenges with Older DAA
 Boceprevir (Victrelis)
 Dygeusia –Anemia – Worse than Pegylated
interferon + Ribavirin alone
 Needs interferon and ribavirin – brings all ADRs
with it too
 4 week lead in period
 Only for Genotype 1 – ie not pangenotypic
 Response guided therapy/stopping rules
 Drug Interactions complex, especially when
treating co-infection
 Large pull burden (12/day), TID frequency
Contraindicated medications
with boceprevir and telaprevir
Drug Class
Contraindicated With BOC[1]
Contraindicated With TVR[2,3]
Alpha 1-adrenoreceptor
antagonist
Alfuzosin
Alfuzosin
Anticonvulsants
Carbamazepine, phenobarbital,
phenytoin
Carbamazepine, phenobarbital,
phenytoin
Antimycobacterials
Rifampin
Rifampin
Ergot derivatives
Dihydroergotamine, ergonovine,
ergotamine, methylergonovine
Dihydroergotamine, ergonovine,
ergotamine, methylergonovine
GI motility agents
Cisapride
Cisapride
Herbal products
St John’s wort
St John’s wort
HMG CoA reductase inhibitors
Lovastatin, simvastatin
Lovastatin, simvastatin
Oral contraceptives
Drospirenone
N/A
Neuroleptic
Pimozide
Pimozide
PDE5 inhibitor
Sildenafil or tadalafil when used
for tx of pulmonary arterial HTN
Sildenafil or tadalafil when used
for tx of pulmonary arterial HTN
Sedatives/hypnotics
Triazolam; orally administered
midazolam
Triazolam; orally administered
midazolam
1. Boceprevir [package insert]. 2013. 2. Telaprevir [package insert]. 2013., 3. www.hep-druginteractions.org
Concurrent Medication
Boceprevir allowed
Telaprevir allowed
Atazanavir/ritonavir (Reyataz®/Norvir®)
No
Yes
Darunavir/ritonavir (Prezista®/Norvir®)
No
No
No, not studied to date
No
No
No
No
Yes, increase TLV dose to
1125mg Q8H
Etravirine (Intelence®)
Yes, reduced etravirine
levels reported
Yes
Rilpivirine (Edurant®)
Yes
Yes
Tenofovir (Viread®)
Yes
Yes, monitor renal fx
Raltegravir (Isentress®)
Yes
Yes
Elvitegravir (in Stribild®)
??
Yes
Dolutegravir (Tivicay®)
Yes
Yes
Maraviroc (Selzentry®)
Yes, MRV 150mg BID
Yes, MRV 150mg BID
Fosamprenavir/ritonavir
(Lexiva®/Norvir®)
Lopinavir/ritonavir (Kaletra®)
Efavirenz (Sustiva®)
Telaprevir
Boceprevir
Simeprevir
Faldapravir
ABT-450
Daclatasvir
Ledipasvir
ABT- 267
Sofosbuvir
ABT-333
Simeprevir FDA Approved
November 22, 2013
 FDA Panel recommended approval October
24, 2013, formal approval November 22,
2013
 Recommend approval of simeprevir, an HCV
NS3/4A protease inhibitor, in combination
with pegylated interferon/ribavirin
 150 mg once-daily for use by genotype 1
hepatitis C patients, either treatment-naive or
prior non-responders, with food
 No dosage recommendations for East Asian
ancestry subjects
Janssen Research and Development. FDA Advisory Committee Recommends Approval of Simeprevir
for Combination Treatment of Genotype 1 Chronic Hepatitis C in Adult Patients. Press release. October 24, 2013.
www.olysio.com. Accessed June 4, 2014.
Simeprevir Key Points
 Q80K mutation screening will be important
 GT1a polymorphism
 Substantial reduction in SVR rates if present at baseline
 Pre-treatment screening recommended
 Serious photosensitivity reactions have been observed
during combination therapy
 Use sun protection measures and limit sun exposure.
Consider discontinuation if a photosensitivity reaction
occurs.
 Rash has been observed during combination therapy
Discontinue OLYSIO if severe rash occurs.
 Caution in Sulfa allergic, simeprevir is a sulfonamide
 Hyperbilirubinemia also reported
Janssen Research and Development. FDA Advisory Committee Recommends Approval of SimeQ*)previr
for Combination Treatment of Genotype 1 Chronic Hepatitis C in Adult Patients. Press release. October 24, 2013.
www.olysio.com. Accessed June 4, 2014.
Simeprevir Key Points
Duration of Treatment with Simeprevir, peg-interferon alfa, ribavirin
Simeprevir, peginterferon alfa +
ribavirin
Peg-interferon alfa Total treatment
+ ribavirin
duration
First 12 weeks
Additional 12
weeks
24 weeks
Prior non-responders, including First 12 weeks
cirrhosis
Additional 36
weeks
48 weeks
Naïve, prior relapser, including
cirrhosis
Simeprevir Stopping Rules
Week 4, > 25IU/mL
Discontinue simeprevir, peg-interferon and ribavirin
Week 12, > 25IU/mL
Discontinue peg-interferon alfa and ribavirin (simeprevir
complete at week 12)
Week 24, > 25IU/mL
Discontinue peg-interferon alfa and ribavirin
Janssen Research and Development. FDA Advisory Committee Recommends Approval of SimeQ*)previr
for Combination Treatment of Genotype 1 Chronic Hepatitis C in Adult Patients. Press release. October 24, 2013.
www.olysio.com. Accessed June 4, 2014.
18
Simeprevir with PEG/RBV, GT 1
HIV/HCV CoInfection Design
Primary Analysis
Treatment naïve or RGT
Prior relapser
Prior partial or
Null responder
SMV + PR
PR
Follow-up
SMV + PR
PR
Follow-up
SMV + PR
PR
Follow-up
12
Dieterich D et al. CROI 2014; Abst 24
24
36
48
60
72
19
Simeprevir + PEG/R,GT1 HIV/HCV
CoInfection: SVR 12 Results, ITT
100
p<0.001
80
87
79
74
70
p<0.001
57
60
40
29
20
0
0
Overall
0
Naives
Dieterich D et al. CROI 2014; Abst 24
Relapsers
0
Partial
5
Null
20
Drug Interactions Considerations
 Simeprevir
 Mild inhibitor of CYP1A2 activity and intestinal
CYP3A4
 Does not affect hepatic CYP3A4 activity
 Inhibits OATP1B1/3 and P-glycoprotein
 Multiple drug interactions expected
www.hcvguidelines.org
Medications to Avoid with Simeprevir
Medication and or Class
Rationale for Avoiding with Simeprevir
Anticonvulsants carbamazepine,
oxcarbazepine,
phenobarbital, phenytoin
Antibiotics – clarithromycin,
erythromycin, telithromycin

Co-administration with these medications is likely to reduce
concentrations of simeprevir and lead to reduced simeprevir
efficacy. Co-administration not recommended.

Antifungals – fluconazole,
itraconazole, ketoconazole,
posaconazole, voriconazole

Antimycobacterials –
rifampin, rifabutin,
rifapentine

Co-administration with these medications is likely to
increase concentrations of either simeprevir or the
antibiotic due to CYP3A4 and P-glycoprotein (P-gp)
inhibition. Co-administration not recommended.
Co-administration with these medications is likely to
increase concentrations of simeprevir due to CYP3A4
inhibition from the antifungals. Co-administration not
recommended.
Co-administration with these medications is likely to reduce
concentrations of simeprevir and lead to reduced simeprevir
efficacy. Co-administration not recommended.
www.nynjaetc.org
Medications to Avoid with Simeprevir
Medication and or Class
Rationale for Avoiding with Simeprevir
Corticosteroids –
dexamethasone

Co-administration with dexamethasone is likely to decrease
concentrations of simeprevir and lead to reduced simeprevir
efficacy. Co-administration not recommended.
Propulsive – cisapride

Co-administration with cisapride may result in increased
concentrations of cisapride leading to potential cardiac
arrhythmias.
Herbal products – Milk
Thistle, St. John’s Wort

Co-administration with milk thistle is likely to increase
concentrations of simeprevir. Co-administration not
recommended.
Co-administration with St. John’s Wort is likely to reduce
concentrations of simeprevir leading to reduced simeprevir
efficacy, due to intestinal P-glycoprotein (P-gp) induction
associated with St. John’s Wort.

www.nynjaetc.org
Simeprevir and HIV Medications
Concurrent Medication
Recommendation
HIV Protease Inhibitors
All HIV PIs

Efavirenz (Sustiva®),
Etravirine (Intelence®),
Nevirapine (Viramune®)

Significant reductions in simeprevir levels and reduced
simeprevir efficacy due to CYP3A4 induction. Coadministration not recommended.
Rilpivirine (Edurant®)

Concurrent use at standard doses acceptable.
Significant increases or decreases in simeprevir levels
expected when used with any HIV protease inhibitor, when
used with or without ritonavir. Co-administration not
recommended
HIV Non Nucleoside Reverse Transcriptase Inhibitors
www.nynjaetc.org
Simeprevir and HIV Medications
Concurrent Medication
Recommendation
HIV Integrase Strand Transfer Inhibitors
Dolutegravir (Tivicay®)
 Concurrent use at standard doses acceptable. Interactions
not expected based upon metabolism of simeprevir.
Elvitegravir (contained in
 Significant increase in simeprevir levels expected when used
Stribild®)
with a cobicistat containing regimen. Co-administration not
recommended.
Raltegravir (Isentress®)
 Concurrent use at standard doses acceptable.
HIV Entry Inhibitors
Maraviroc (Selzentry®)
 Concurrent use at standard doses acceptable. Interactions
not expected based upon metabolism of simeprevir.
HIV Nucleoside/Nucelotide Reverse Transcriptase Inhibitors
All NRTIs
 Concurrent use at standard doses acceptable. Interactions
not expected based upon metabolism of simeprevir.
www.nynjaetc.org
Sofosbuvir FDA Approved,
December 6, 2013
 FDA Panel recommended approval
October 25, 2013
 Recommendation covers both use with
interferon-based therapy for treatmentnaive people with HCV genotypes 1 or 4
 Also use in dual therapy with ribavirin for
people with easier-to-treat HCV genotypes
2 or 3 - the first approved interferon-free
regimen
Gilead Sciences. FDA Advisory Committee Supports Approval of Gilead’s Sofosbuvir for Chronic
Hepatitis C Infection. Press release. October 25, 2013. www.solvadi.com. Accessed June 4, 2014.
Sofosbuvir Key Points
 Indication
 NS5B nucleotide polymerase inhibitor for the treatment of
chronic HCV as a component of combination anitiviral treatment
regimen
 400 mg tablet, once daily dosing, with no food restrictions
HCV Mono-infected and
HCV/HIV Co-infected
Treatment
Duration
Sofosbuvir + PEG-interferon
+ ribavirin
12 weeks
Genotype 2
Sofosbuvir + ribavirin
12 weeks
Genotype 3
Sofosbuvir + ribavirin
24 weeks
Genotype 1 or 4
www.solvadi.com. Accessed June 4, 2014.
27
Sofosbuvir Key Points
 Sofosbuvir + ribavirin ALONE for 24 weeks
can be considered for GT1 if intolerant to
interferon
 No dosage recommendation can be made
in patients with severe renal impairment or
ESRD – up to 20 fold increase in SOF
metabolite
 Contraindications – Monotherapy, also
ribavirin birth defects
www.solvadi.com. Accessed June 4, 2014.
Sofosbuvir Key Points
 Adverse Events
 Headache and fatigue most common
 Anemia and insomnia, nausea when adding
peginterferon + ribavirin
 Additional info
 HIV/HCV coinfection studied, also data on
patients with HCC awaiting liver transplantation
studied
 Drug Interactions
 Intestinal PGP inducers likely to reduce levels –ie
rifampin, St Johns Wort
www.solvadi.com. Accessed June 4, 2014
PHOTON-1 Trial in HIV/HCV
Co-infection
• Open-label, phase 3 study of sofosbuvir plus weightbased ribavirin in coinfection, genotypes 1, 2 or 3.
Week 0
GT1,
Naive
12
24
36
48
SOF + RBV, n=114
GT2/3, Naive
SOF + RBV, n=68
GT2/3,
Experienced
SOF + RBV, n=41
Naggie S et al. CROI 2014; Abst 26.
SVR 12
SVR 24
30
PHOTON-1: Results
Naggie S et al. CROI 2014; Abst 26
31
PHOTON-1: Results
 Allowable ARVs: NRTIs, atazanavir/r,
darunavir/r, rilpivirine & raltegravir
 Most virologic failures had relapse
 No sofosbuvir resistance seen
Naggie S et al. CROI 2014; Abst 26
32
PHOTON-1 Adverse Events
Patients, % AEs
24 Weeks SOF+RBV(n=155)
12 Weeks SOF+RBV(n=68)
Fatigue
39
35
Insomnia
15
21
Headache
14
13
Nausea
15
18
Diarrhea
11
9
Irritability
10
10
URI
12
12
Grade 3-4 AEs
12
10
Serious AEs
6
7
Treatment DC due to AEs
3
4
Death
0
1
Naggie S et al. CROI 2014; Abst 26
33
Drug Interactions Considerations
 Sofosbuvir
 Substrate for P-glycoprotein and breast
cancer resistance protein
 Intracellular metabolism mediated by
hydrolase and nucleotide phosphorylation
pathways
 Minimal drug interactions expected
www.hcvguidelines.org
Medications to Avoid with Sofosbuvir
Medication and or Class
Rationale for Avoiding with Sofosbuvir
Anticonvulsants –

carbamazepine,
oxcarbazepine,
phenobarbital, phenytoin
Co-administration with these medications is likely to reduce
concentrations of sofosbuvir leading to reduced sofosbuvir
efficacy. Co-administration not recommended.
Antimycobacterials –
rifampin, rifabutin,
rifapentin

Co-administration with these medications is likely to reduce
concentrations of sofosbuvir leading to reduced sofosbuvir
efficacy due to intestinal P-glycoprotein (P-gp) induction
from rifampin.
Herbal products – St.
John’s Wort

Co-administration with these medications is likely to reduce
concentrations of sofosbuvir leading to reduced sofosbuvir
efficacy due to intestinal P-glycoprotein (P-gp) induction
associated with St. John’s Wort.
www.nynjaetc.org
Sofosbuvir and HIV Medications
Concurrent Medication
Recommendation
HIV Protease Inhibitors
All HIV PIs, with or without  Concurrent use at standard doses acceptable. Interactions not
ritonavir, except tipranavir
expected based upon metabolism of sofosbuvir.
Tipranavir (Aptivus®)
 Co-administration not recommended
HIV Non Nucleoside Reverse Transcriptase Inhibitors
All NNRTIs
 Concurrent use at standard doses acceptable.
www.nynjaetc.org
Sofosbuvir and HIV Medications
Concurrent Medication
Recommendation
HIV Integrase Strand Transfer Inhibitors
Dolutegravir (Tivicay®)
 Concurrent use at standard doses acceptable. Interactions not
expected based upon metabolism of sofosbuvir.
Elvitegravir (contained in  Concurrent use at standard doses acceptable. Interactions not
Stribild®)
expected based upon metabolism of sofosbuvir.
Raltegravir (Isentress®)
 Concurrent use at standard doses acceptable.
HIV Entry Inhibitors
Maraviroc (Selzentry®)
 Concurrent use at standard doses acceptable. Interactions not
expected based upon metabolism of sofosbuvir.
HIV Nucleoside/Nucleotide Reverse Transcriptase Inhibitors
All NRTIs
 Concurrent use at standard doses acceptable. Interactions not
expected based upon metabolism of sofosbuvir.
www.nynjaetc.org
COSMOS Study Design
Randomized
2:1:2:1
Arm1
SMV+SOF+RBV
Post-treatment follow-up
Arm2
SMV+SOF
Post-treatment follow-up
Arm 3
SMV+SOF
+ RBV
Post-treatment follow-up
Arm 4
SMV+SOF
Post-treatment follow-up
12
24
36
48
Cohort 1 – Metavir F0-F2, prior null responders
Cohort 2 – Metavir F3-F4, prior null responders or naives
Primary Endpoint: SVR12
Secondary Endpoints: RVR, Tx failure, relapse rate, safety
Lawitz, etal. 49th EASL, April 9-13, 2014.
38
COSMOS, Baseline Characteristics
Characteristic
SMV/SOF+
RBV
24 weeks
n=30
SMV/SOF
24 weeks
n=16
SMV/SOF +
RBV 12
weeks
n=27
SMV/SOF
12 weeks
n=14
Total
n=87
70
44
74
71
67
97/3
81/19
93/7
86/14
91/9
Hispanic, Latino
10
31
19
14
17
Median Age
58
58
57
58
58
Median BMI
28
29
27
32
28
GT 1a
77
75
82
79
78
GT 1a, Q80K
48
42
36
30
40
Median HCV VL
6.3
6.6
6.7
6.7
6.6
Null Responders
57
50
56
50
54
IL28B, non CC
73
88
85
71
79
Cirrhosis
43
63
41
50
47
Male, %
White/African American
Lawitz, etal. 49th EASL, April 9-13, 2014.
39
COSMOS, SVR 12 (ITT) Results
100%
0
7
7
7
2
80%
60%
Relapse
100
93
93
93
95
40%
Non VF
SVR12
20%
0%
28/30
16/16
25/27
13/14
82/87
SMV/SOF/RBV
SMV/SOF
SMV/SOF/RBV
SMV/SOF
SMV/SOF +/- RBV
24 weeks
Lawitz, etal. 49th EASL, April 9-13, 2014.
12 weeks
Overall
40
www.hcvguidelines.org
Released 1/29/14!
HIV/HCV Co-Infection, GT1
Preferred
Alternative
Treatment-naïve, prior PEG/RBV
relapsers, IFN eligible:
SOF + PEG/RBV(WB) x 12 weeks
Treatment-naïve, prior PEG/RBV
relapsers, IFN eligible:
SMV x 12 weeks + PEG/RBV(WB) x 24
weeks
IFN ineligible:
None
IFN ineligible:
SOF + RBV(WB) x 24 weeks
SOF + SMV ± RBV(WB) x 12 weeks
Treatment experienced, prior PEG/RBV
nonresponders, regardless of IFN
eligibility:
SOF + SMV ± RBV(WB) x 12 weeks
Treatment experienced, prior PEG/RBV
nonresponders
IFN eligible: SOF + PEG/RBV(WB) x 12
Weeks
IFN ineligible: SOF + RBV(WB) x 24
Weeks
Not Recommended:
TVR + PEG/RBV x 24 or 48 weeks (RGT), BOC + PEG/RBV x 28 or 48 weeks (RGT)
PEG/RBV x 48 weeks, SMV x 12 weeks + PEG/RBV x 48 wks
www.hcvguidelines.org
HIV/HCV Co-Infection, GT2
Preferred
Alternative
All patients, regardless of treatment
history:
SOF + RBV(WB) x 12 weeks
Treatment naive and prior PEG/RBV
relapsers:
None
Treatment experienced, prior PEG/RBV
Nonresponders:
IFN eligible: SOF + PEG/RBV(WB) X 12
Weeks
IFN ineligible: None
Not Recommended:
PEG/RBV x 24-48 weeks, or any regimen with TVR, BOC, or SMV
www.hcvguidelines.org
HIV/HCV Co-Infection, GT3
Preferred
Alternative
All patients, regardless of treatment
history:
SOF + RBV(WB) x 24 weeks
Treatment naïve, PEG/RBV relapsers:
None
Treatment experienced, prior PEG/RBV
Nonresponders:
IFN eligible: SOF + PEG/RBV(WB) X 12
weeks
IFN ineligible: None
Not Recommended:
PEG/RBV x 24 - 48 weeks, Any regimen with TVR, BOC, or SMV
www.hcvguidelines.org
HIV/HCV Coinfection, GT4
Preferred
Alternative
All patients, regardless of treatment
history:
None
IFN eligible: SOF + PEG/RBV(WB) x 12
weeks
IFN ineligible: SOF + RBV(WB) x 24
weeks
Not Recommended:
PEG/RBV x 48 weeks, any regimen with TVR or BOC
www.hcvguidelines.org
HIV/HCV Coinfection, GT 5,6
Preferred
Alternative
All patients, regardless of treatment
history:
SOF + PEG/RBV(WB) x 12 weeks
None
Not Recommended:
PEG/RBV x 48 weeks, any regimen with TVR, BOC, or SMV
www.hcvguidelines.org
Standard Dosing




Sofosbuvir – 400mg once daily
Simeprevir – 150mg once daily
Peg Interferon – 180mcg once weekly
Ribavirin – weight based dosing
 <75kg – 1000mg daily in divided doses
 ≥75 kg – 1200mg daily in divided doses
www.hcvguidelines.org
IFN Ineligible Definitions
 Intolerance to IFN
 Autoimmune hepatitis and other autoimmune
disorders
 Hypersensitivity to PEG or any of its components
 Decompensated hepatic disease
 History of depression, or clinical features
consistent with depression
 A baseline neutrophil count below 1500/μL, a
baseline platelet count below 90,000/μL or
baseline hemoglobin below 10 g/dL
 A history of preexisting cardiac disease
www.hcvguidelines.org
Investigational HCV Medications
Select Investigational Medications
 All oral, interferon free likely in October 2014
 Ledipasvir (FDC with sofosbuvir)
 ABT-450/ritonavir+ABT-267 (ombitasvir) (FDC)
plus ABT-333 (dasabuvir) BID
 Other meds moving forward (not all inclusive)




Daclatasvir + asunaprevir + BMS-791325
Faldaprevir
MK-5172, MK-8742
GS-9669, GS-9451, GS-5816
50
Select HIV/HCV Resources
www.hcvguidelines.org
Released 1/29/14!
www.nynjaetc.org
www.nynjaetc.org
CLICK HERE
www.nynjaetc.org
CLICK HERE
NY/NJ AETC – www.nynjaetc.org
NY/NJ AETC – www.nynjaetc.org
www.hep-druginteractions.org
NY/NJ AETC – www.nynjaetc.org
NY/NJ AETC – www.nynjaetc.org

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