Lucas A. Hill, PharmD Clinical Instructor University of California San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences San Diego, California Drug-Drug Interactions Between Antiretrovirals and the HCV Treatments in HIV/HCV Coinfection Management AU EDITED: 09/01/15 New York, NY: September 9, 2015 ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ Slide 2 of 50 Financial Relationships With Commercial Entities Dr Hill has no relevant financial affiliations to disclose. (Updated 09/01/15) ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ Slide 3 of 50 Learning Objectives After attending this presentation, participants will be able to describe: Available efficacy data for treatment of HCV in HIV/HCV coinfected patients Important drug interactions between HIV antiretrovirals and HCV direct acting antivirals Future therapies for the treatment of HCV in HIV/HCV coinfection ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ ___________________________________ New York, NY: September 9, 2015 1
18
Embed
Learning Objectives - IAS- · PDF fileNew York, NY: September 9, 2015 1. Slide 4 of 50 Potential issues in treating HIV/HCV ... Efavirenz + FTC + TDF 160 (48) Raltegravir + FTC + TDF
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Lucas A. Hill, PharmDClinical Instructor
University of California San Diego Skaggs School of Pharmacy and
Pharmaceutical SciencesSan Diego, California
Drug-Drug Interactions Between
Antiretrovirals and the HCV Treatments in
HIV/HCV Coinfection Management
AU EDITED: 09/01/15
New York, NY: September 9, 2015
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 2 of 50
Financial Relationships With Commercial Entities
Dr Hill has no relevant financial affiliations to
disclose. (Updated 09/01/15)
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 3 of 50
Learning Objectives
After attending this presentation, participants will be
able to describe:
Available efficacy data for treatment of HCV in
HIV/HCV coinfected patients
Important drug interactions between HIV
antiretrovirals and HCV direct acting antivirals
Future therapies for the treatment of HCV in
HIV/HCV coinfection
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
New York, NY: September 9, 2015 1
Slide 4 of 50
Potential issues in treating HIV/HCV co-infection with new HCV antivirals
HCV Therapy in
HCV/HIV
Efficacy
ProvidersAccess
D-D-I
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 5 of 50
MD (evaluation, assessment, treatment planning)
Clinic Pharmacist (treatment planning, follow-up)
Health Educator, Drug and Alcohol Counselor (rehab, lifestyle changes)
• ARV History– Zidovudine, didanosine, zalcitabine during 1980s– Stavudine, nelfinavir, ritonavir during 1990s– Tenofovir, lamivudine, efavirenz 12/2003 – 5/2007– Tenofovir/emtricitabine/efavirenz (FDC) since 5/2007 to
present• HIV-1 viral load undetectable since 2003
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 8 of 50
HCV History• Treatment history:
Failed peginterferon/ribavirin x 2 (relapsed after 42 wks)
• ART regimens included emtricitabine and tenofovir disoproxil fumarate plus efavirenz, raltegravir, or rilpivirine
Wk 0 Wk 12 Wk 24
SVR12LDV/SOFN=335
Naggie S, Cooper C, Saag M, et al. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015; 373:705-713.
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
New York, NY: September 9, 2015 5
Slide 16 of 50ION-4 Results: Demographics and Baseline Characteristics
LDV/SOF 12 weeksN=335
Mean age, y (range) 52 (26-72)
Male, n (%) 276 (82)
Black, n (%) 115 (34)
Hispanic or Latino, n (%) 56 (17)
Mean BMI, kg/m2 (range) 27 (18-66)
IL28B CC, n (%) 81 (24)
GT 1 327 (98)
HCV treatment experienced, n (%) 185 (55)
Cirrhosis, n (%) 67 (20)
Mean HCV RNA, log10 IU/mL ± SD 6.7 ± 0.6
Median CD4 cell count, cells/µL (range) 628 (106-2069)
HIV ARV Regimen
Efavirenz + FTC + TDF 160 (48)
Raltegravir + FTC + TDF 146 (44)
Rilpivirine + FTC + TDF 29 (9)
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 17 of 50
96 95 97 96 94
0
20
40
60
80
100
Naïve vs ExperiencedOverall Cirrhosis Status
LDV/SOF 12 Weeks
ExperiencedNaïve No Cirrhosis Cirrhosis
321/335 142/150 179/185 63/67258/268
SV
R12 (
%)
Results: SVR12 by Prior TreatmentExperience and Cirrhosis Status
Overall
Error bars represent 95% confidence intervals.
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 18 of 50
ION-4 Results: Renal FunctionEFV+FTC+TDF (n=160)
RAL+FTC+TDF (n=146)
RPV+FTC+TDF (n=29)
LDV/SOF +
60708090
100110120130140150
Cre
atin
ine
Cle
aran
ce(m
L/m
in),
mea
n
SD
WeekBL 1 2 4 6 8 10 12 FU-4
4 patients (1%) had change in creatinine ≥ 0.4 mg/dL
– 2 completed treatment with no ART change
– 1 had dose reduction of TDF, 1 discontinued TDF
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
New York, NY: September 9, 2015 6
Slide 19 of 50
SVR12ABT450/r/267 + 333 + R
ABT450/r/267 + 333 + R
12 24Weeks
SVR12
N=31
N=32
• Stable ART
– ATV or RAL
– HIV RNA <40 copies/mL
– CD4 >200
Wyles. EASL 2014.
.
12 Week 24 Week
Male 94% 91%
Naïve 65% 69%
Null 16% 16%
1a 87% 91%
F4 19% 19%
CD4 633 625
TURQUOISE I: PrOD + RBV in HIV/HCV
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 20 of 50
TURQUOISE I: PrOD + RBV in HIV/HCV
• In 12-week arm 1 patient withdrew consent• Two patients in 24-week arm were re-infected causing decrease to 90.6% at SVR12• Two virologic failures — both 1a cirrhotic null responders, both on raltegravir
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 21 of 50Daclatasvir-ALLY-2
■ Primary endpoint: SVR12 in treatment-naive patients with GT 1 treated for 12 weeks
■ Standard DCV dose is 60 mg– Dose-adjusted for concomitant ARV therapy: 30 mg with ritonavir-boosted PIs, 90 mg with
NNRTIs except RPV* HCV RNA <LLOQ (TD or TND) at posttreatment Week 12, assessed using the Roche HCV COBAS TaqMan Test v2.0 (LLOQ 25 IU/mL).
DCV 30/60/90 mg +SOF 400 mg QD
24
DCV 30/60/90 mg +SOF 400 mg QD
12
NaiveRandomize 2:1
Experienced
DCV 30/60/90 mg + SOF 400 mg QD
Week 0 8
N
101
50
52
SVR12*
Wyles D, Ruane P, Sulkowski M, et al. Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015;373:714-725.
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
New York, NY: September 9, 2015 7
Slide 22 of 50Slide 22 of 50
Demographic and HCV Disease CharacteristicsDemographic and HCV Disease Characteristics
ParameterNaive
12 WeekN = 101
Experienced12 Week
N = 52
Naive8 WeekN = 50
Age, median years (range) 52 (24–71) 57 (43–66) 50 (28–75)
Audience Response Question• Based on the patient’s ARV regimen of
tenofovir/emtricitabine/efavirenz, which treatment regimen would allow the patient to remain on his current ARVs and start HCV treatment.
1. Paritaprevir/ritonavir/ombitasvir + dasabuvir + ribavirin x 24 weeks
2. Sofosbuvir + daclatasvir + ribavirin x 24 weeks
3. Ledipasvir/sofosbuvir x 24 weeks
4. Sofosbuvir + simeprevir x 24 weeks
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 45 of 50
Which DAA regimen with which HAART regimenSOF/RBV SOF/SMV SOF/LDV SOF/DCV PrOD/RBV
TDF
ABC, 3TC, FTC
DRV/RTVCaution only if with TDF
ATV/RTVCaution only if with TDF
Use 30mg dose
EFVCaution when using with TDF
Use 90mg dose
ETR No data Use 90mg dose No data
RPV
RAL
EVG/COBI/TDF/FTC
Can consider with TAF No data No data
DTG No data No data
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
New York, NY: September 9, 2015 15
Slide 46 of 50
Investigational Therapies
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 47 of 50
C-EDGE• All patients treated with Grazoprevir (PI)/Elbasvir (NS5A)
fixed dose combination for 12 weeks
• Co-infected, genotype 1, 4, and 6 treatment naïve patients with and without cirrhosis
• Naïve to ART with CD4 > 500 cells/mm3 and HIV RNA < 50k copies/mL or on stable ART with undetectable viral load and CD4 >200
• ART allowed was tenofovir or abacavir + emtricitabine or lamivudine + rilpivirine, raltegravir, or dolutegravir
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 48 of 50
Demographics
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
New York, NY: September 9, 2015 16
Slide 49 of 50
C-EDGE results
• Well tolerated, most common side effects were headache, nausea, and fatigue
• Anticipate will not be able to use with efavirenz- or ritonavir-boosted protease inhibitors
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 50 of 50
Regimen Switching in the Setting of Viral Suppression Prior to Starting Hep
C Treatment• Cardinal principle of regimen switching
– Maintain viral suppression without jeopardizing future options
• Virologic failure with emergence of new resistance mutations
– Increases need for more complex, difficult-to-follow, or expensive regimens
DHHS. http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Revision May 1, 2014.
Panel on Antiretroviral Guidelines for Adult and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. May 1, 2014;1-285. http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 51 of 50Principles for Successful Regimen Switching
• Review ART history
– Virologic suppression, resistance test results, and past adverse events
– If resistance data are unavailable, resistance may often be inferred by treatment history
– Consult with an HIV specialist for patients with a history of resistance >1 drug classes
• During first 3 months after a regimen switch
– More intensive monitoring of tolerability, viral suppression, adherence, and laboratory changes is recommended
DHHS. http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Revision May 1, 2014.
Panel on Antiretroviral Guidelines for Adult and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. May 1, 2014;1-285. http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
New York, NY: September 9, 2015 17
Slide 52 of 50
Monitoring After Switching Regimens• Evaluate more closely for several months after a treatment switch
– 1 to 2 weeks post switch: a clinic visit or phone call
– 4 to 8 weeks post switch: viral load test (rebound viremia)
• Goal of the intensive monitoring
– Assess medication tolerance
– Conduct targeted laboratory testing within 3 months after the regimen switch (ie, pre-existing laboratory abnormalities or potential concerns with the new regimen)
• Absent any specific complaints, laboratory abnormalities, or evidence of viral rebound at this 3-month visit, clinical and laboratory monitoring of the patient may resume on a regularly scheduled basis
DHHS. http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Revision May 1, 2014.
Panel on Antiretroviral Guidelines for Adult and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. May 1, 2014;1-285. http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Slide 53 of 50
Summary
• Efficacy in HIV/HCV co-infection patients treated with DAAs appears to mimic efficacy seen in mono-infected patients
• Drug interactions and management have become easier in HCV treatment but still exist
• Remains “unique” population due to frequent complex drug regimens and co-morbid conditions
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
IAS–USA
An IAS–USA State-Of-The-Art Clinical Conference on the