Post on 24-Jul-2015
February 23-26, 2015Seattle, Washington
HIV/AIDS Seattle UpdateCCO Independent Conference Coverageof the 2015 Conference on Retroviruses and Opportunistic Infections*
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This program is supported by an educational grant from
This program is supported by educational grants fromGilead Sciences, Merck, and ViiV.
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Faculty
Joseph J. Eron, Jr., MDProfessor of Medicine and EpidemiologyUniversity of North Carolina School of MedicineDirector, AIDS Clinical Trials UnitUniversity of North CarolinaChapel Hill, North Carolina
Joel E. Gallant, MD, MPHMedical Director of Specialty Services Southwest CARE CenterSanta Fe, New MexicoAdjunct Professor of MedicineDivision of Infectious DiseasesJohns Hopkins University School of MedicineBaltimore, Maryland
Kathleen E. Squires, MDW. Paul and Ida H. Havens Professor of Infectious DiseasesDirector, Division of Infectious DiseasesSidney Kimmel Medical College of Thomas Jefferson UniversityPhiladelphia, Pennsylvania
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Disclosures
Joseph J. Eron, Jr., MD, has disclosed that he has received consulting fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV, Merck, Tibotec/Janssen, and Tobira; and has received funds for research support from GlaxoSmithKline/ViiV.
Joel E. Gallant, MD, has disclosed that he has received consulting fees from Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and ViiV and funds for research support from AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV, Janssen, Merck, and Sangamo Biosciences.
Kathleen E. Squires, MD, has disclosed that she has received funds for research support paid to Thomas Jefferson University from Gilead Sciences and has served on advisory boards for Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and ViiV.
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PROUD: Immediate vs Deferred PrEP in High-Risk MSM in “Real World” Trial Randomized, open-label trial of daily
oral TDF/FTC PrEP in HIV- MSM in 13 clinics in London
– Immediate (n = 267) vs
– Deferred for 12 mos (n = 256)
Primary endpoint: HIV infection in first 12 mos
86% reduction in risk seen over 60 wks with immediate PrEP (90% CI: 58% to 96%, P = .0002)
– Rate difference: 7.6 (90% CI: 4.1-11.2)
– Number needed to treat to prevent 1 infection: 13 (90% CI: 9-25)
2 of 3 infected persons in immediate group seroconverting at study entry or shortly after first dose of PrEP
M184V/I observed in 3/6 patients who seroconverted
– No K65R observed
High rate of STIs seen in both groups
DMSB interrupted trial; recommended that all participants be offered PrEP
HIV Incidence
Group Infected, nIncidence/100 PY (90% CI)
Immediate 3 1.3 (0.4-3.0)
Deferred 19 8.9 (6.0-12.7)
McCormack S, et al. CROI 2015. Abstract 22LB.Reproduced with permission.
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0.20
0.16
0.12
0.08
0.04
0.000 2 4 6 8 10 12 14 16 18 20 22 24 26
Mos
ANRS Ipergay: On-Demand Oral PrEP in High-Risk MSM Randomized double-blind trial of event-
driven oral TDF/FTC* (n = 199) vs placebo (n = 201) (both with prevention services) in France
– 2 tablets taken 2-24 hrs before sex
– 1 tablet 24 hrs after sex
– 1 tablet 48 hrs after first event-driven dose
Primary endpoint: HIV seroconversion
86% reduction in risk seen in PrEP arm (95% CI: 40% to 99%, P = .002)
– Number needed to treat for 1 yr to prevent 1 infection: 18
– Median of 16 pills taken per mo in each arm
In pts with infection, no TFV found in serum in last 2 visits
4 cases of acute HCV infection noted among lab abnormalities
DSMB stopped trial early and recommended all participants start PrEPMolina JM, et al. CROI 2015. Abstract 23LB.
Reproduced with permission.
*On-demand PrEP strategy not FDA approved.
2 infections; incidence 0.94/100 PY
14 infections; incidence 6.6/100 PY
201199
141140
7482
5558
4143
Pts at Risk, nPlaceboTDF/FTC
Placebo
TDF/FTC
P = .002
Pro
bab
ilit
y o
f H
IV
Infe
ctio
n
Kaplan-Meier Estimate of Time to HIV Infection
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Oral PrEP + ART as Prevention in High-Risk Serodiscordant Couples Partners Demonstration Project in Africa
– Oral daily TDF/FTC PrEP for HIV-uninfected partner in serodiscordant couple continued 6 mos beyond initiation of ART for infected partner
– High-risk couples defined as younger age, fewer children, uncircumcised HIV-negative male, cohabitating, unprotected sex in past mo, high HIV-1 RNA in HIV-positive partner
Interim analysis
– > 95% of HIV-negative partners using PrEP
– 80% of HIV-positive partners have initiated ART; of these, > 90% with suppression
96% reduction in expected infections
‒ IRR, expected vs observed: 0.04 (95% CI: 0.01-0.19; P < .0001)
In pts with seroconversion, no TFV detectable in plasma at time of seroconversion
– HIV-positive partner in 1 couple not on ART (high CD4+ count)
– Other couple dissolved and HIV-negative partner in new relationship
Baeten J, et al. CROI 2015. Abstract 24. Reproduced with permission.
HIV Incidence, Actual vs Expected
Group Infected, nIncidence/100 PY
(95% CI)
Expected 39.7 5.2 (3.7-6.9)
Actual 2 0.2 (0-0.9)
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Medical Cost Savings Associated With HIV Prevention in the United States Cost modeling analysis of the Medical Expenditure Panel
Survey
Investigators used Cost-Effectiveness of Preventing AIDS Complications Model to project discounted lifetime medical costs, assuming HIV infection at 35 yrs of age
The medical cost savings of averting 1 HIV infection was found to be $229,800
Cost savings are higher if taking secondary infections into account and lower if infection is delayed vs totally averted
Schackmann R, et al. CROI 2015. Abstract 1104.
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PROMISE: Randomized Trial of PMTCT Strategies: Antepartum Component Multinational trial in HIV-positive pregnant women in India and Africa
Primary endpoint: HIV infection in infant
– MTCT through neonatal 14 days of age significantly lower in triple ART arms
– Difference: -1.28% (95% CI, -2.11% to -0.44%)
Fowler MG, et al. CROI 2015. Abstract 31LB.
ZDV + sdNVP + TDF/FTC tail
TDF/FTC + LPV/RTV*
ZDV/3TC + LPV/RTV
HIV-positive pregnant women Gestational age ≥ 14 wksNo triple ART in current
pregnancyDid not meet country
eligibility for ARTCD4+ ≥ 350 or country
threshold for ARTCrCl > 60
No active TB(N = 3529)
MTCT, % (infections/births)
1.8 (25/1326)
0.56 (9/1710)†
*In Version 2 of the protocol, only HBV-positive women in TDF/FTC arm. †Combined triple ARV arms.
Primary Endpoint ResultsAntepartum component14 days postdelivery
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PROMISE: Less MTCT but Adverse Events Greater in Triple ART Arms Higher moderate, but not severe, adverse pregnancy outcome with triple ARV
– Severe outcomes less in ZDV/3TC arm vs TDF/FTC arm
– Lower risk of infant death with ZDV/3TC vs TDF/FTC: 0.6% (2/346) vs 4.4% (15/341), P = .001
– Primarily among deaths in infants < 34 wks of gestational age
Fowler MG, et al. CROI 2015. Abstract 31LB. Reproduced with permission.
ZDV (Arm A)ZDV/3TC + LPV/RTV (Arm B)TDF/FTC + LPV/RTV (Arm C)
40
30
20
10
0
Moderate Adverse Outcomes Severe Adverse Outcomes
27
3835
2017
9
20
9 7
4
19
13
63 3210
B vs CP = .02 B vs C
P = .04
A vs CP = .004
A vs CP = .04
% W
ith
Eve
nt
Any < 37 WkGest. Age
Any < 34 WkGest. Age
< 2500 gBirth Wt
< 1500 gBirth Wt
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Studies 104/111: Tenofovir Alafenamide Fumarate vs TDF in Treatment-Naive Pts Parallel, randomized, double-blind, active-controlled phase III studies
Primary endpoint: HIV-1 RNA at Wk 48
TAF/FTC/EVG/COBI*single-tablet regimen
(n = 866)
TDF/FTC/EVG/COBI†
single-tablet regimen(n = 867)
Treatment-naive HIV-infected pts with
HIV-1 RNA ≥ 1000 copies/mL,eGFR ≥ 50 mL/min
(N = 1733)
Stratified by HIV-1 RNA, CD4+ cell count, geographic region
Wk 48Primary endpoint Wk 144
*10/200/150/150 mg once daily.†300/200/150/150 mg once daily.
Wohl DA, et al. CROI 2015. Abstract 113LB.
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Virologic Success*
Virologic Failure
No Data
Studies 104/111: TAF Noninferior to TDF at Week 48
TAF also noninferior to TDF at Wk 48 in each study (104 and 111)
Results similar across all baseline virologic and demographic subgroups
7 pts in TAF arm and 5 pts in TDF arm with NRTI resistance at VF
– 1 in TAF arm and 2 in TDF arm with combined M184V/I + K65R
5 pts in TAF arm and 3 pts in TDF arm with INSTI resistance at VF
0.9% in TAF arm and 1.5% in TDF arm discontinued due to AE
CD4+ increases greater in TAF arm: 211 vs 181 (P = .024)
Pts
(%
)
9290
Δ +2.0%(95% CI: -0.7% to +4.7)
TAF/FTC/EVG/COBI (n = 866)TDF/FTC/EVG/COBI(n = 867)
0
20
40
60
80
100
4 4 4 6n =
*HIV-1 RNA < 50 c/mL as defined by FDA Snapshot algorithmDiscontinued for AE, death, or missing data.
800 784
Wohl DA, et al. CROI 2015. Abstract 113LB. Reproduced with permission.
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Renal Markers With TAF and TDF at Wk 48
Smaller decreases in eGFR with TAF[1]
Smaller changes in proteinuria with TAF[1]
In separate single-arm trial of virologically suppressed pts with eGFR 30-69 mL/min switched to open-label TAF/FTC/EVG/COBI[2]
– 65% on TDF at BL
At Wk 48 after switch:
– 92% maintained virologic suppression
– No change in eGFR
– Reduction in proteinuria and markers of renal tubular function
– Improvement in hip and spine BMD
1. Sax P, et al. CROI 2015. Abstract 143. Reproduced with permission. 2. Pozniak A, et al. CROI 2015. Abstract 795.
P < .0012010
0-10-20
0 12 24 36 48
Time (Wks)
-6.6-11.2
Mea
n Δ
Fro
m B
L i
n e
GF
R,
mL
/min
(C
ock
cro
ft-G
ault
) TAF/FTC/EVG/COBI (n = 866)TDF/FTC/EVG/COBI (n = 867)
Median % Change From BL in Urine Protein:Creatinine Ratio
MarkerTAF
(n = 866)
TDF (n = 867)
P Value
Protein -3 +20 < .001
Albumin -5 +7 < .001
Retinol-binding protein +9 +51 < .001
β2-microglobulin -32 +24 < .001
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Studies 104/111: Significantly Smaller Decline in Hip and Spine BMD With TAF Significantly smaller decline in hip and spine BMD with TAF
Higher lipid levels with TAF, but TC:HDL-C ratio same as TDF[1]
0 24 48 0 24 48-8
-6
-4
-2
0
2
Wk Wk
-8
-6
-4
-2
0
2
= 845= 850
797816
784773
836848
789815
780767
-1.30-2.86
-0.66
-2.95
P < .001 P < .001
Mea
n %
Ch
ang
e F
rom
BL
Sax P, et al. CROI 2015. Abstract 143. Reproduced with permission.
n n
TAF/FTC/EVG/COBI (n = 866)TDF/FTC/EVG/COBI (n = 867)
Change in Spine BMD Change in Hip BMD
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LATTE: Cabotegravir (GSK1265744) + RPV as Maintenance ART: Wk 96 Results Cabotegravir, DTG analogue with long half-life, oral or injectable formulations
Randomized, dose-ranging phase IIb study of oral formulation
Primary endpoint: HIV-1 RNA < 50 c/mL at Wk 48
CAB 10 mg QD + RPV 25 mg QD
CAB 30 mg QD + RPV 25 mg QD
*Pts with HIV-1 RNA < 50 c/mL at Wk 24 continued to maintenance phase.TDF/FTC or ABC/3TC.
ART-naive pts,HIV-1 RNA ≥ 1000 c/mL
(N = 243) CAB 60 mg QD + RPV 25 mg QD
EFV 600 mg QD + 2 NRTIs QD (n = 62)
Margolis D, et al. CROI 2015. Abstract 554LB.
CAB 10 mg QD + 2 NRTIs
(n = 60)
CAB 30 mg QD + 2 NRTIs
(n = 60)
CAB 60 mg QD + 2 NRTIs
(n = 61)
Wk 48primary analysis
Stratified by HIV-1 RNA (≤ vs > 100,000 c/mL) and NRTI Wk 24
Induction Phase* Maintenance Phase
Wk 96
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LATTE: Virologic Success Through Maintenance Wk 96
6 pts in CAB arms with PDVF at Wk 96; 4 additional pts since Wk 48
– 3 pts in CAB 10-mg arm with treatment-emergent NNRTI resistance; 1 of these with both NNRTI + INSTI RAMs but decreased ARV exposure in PK analysis
Margolis D, et al. CROI 2015. Abstract 554LB. Reproduced with permission.
HIV
-1 R
NA
< 5
0 c/
mL
by
Sn
apsh
ot
Alg
ori
thm
(%
)
100
80
60
40
20
0BL 4 12 24 28 36 48 72 96
Induction Phase Maintenance Phase
CAB 10 mg (n = 60)CAB 30 mg (n = 60)*CAB 60 mg (n = 61)EFV 600 mg (n = 62)
68%63%
84%
75%
Wks*CAB 30 mg selected for future development
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BMS-955176: Investigational Second-Generation Maturation Inhibitor BMS-955176 binds tightly and
reversibly to HIV-1 Gag with greater potency and coverage of Gag polymorphs than first-generation maturation inhibitors
– Low-dose with half-life supportive of once-daily dosing
– Low serum binding
– No significant safety issues in early clinical studies
Antiviral activity measured over 10 days in placebo-controlled study
– HIV-infected treatment-naive and experienced pts with HIV-1 RNA ≥ 5000 and CD4+ count ≥ 200
All doses ≥ 10 mg associated with HIV-1 RNA declines over dosing period
– Median change in HIV-1 RNA from BL to Day 11: 1.4 log10 c/mL
No serious AEs; no discontinuations due to AEs over study period
Hwang C, et al. CROI 2015. Abstract 114LB. Reproduced with permission.
1 2 3 4 5 6 7 8 91011 13 25
Dosing period
Study Days
1
0
-1
-1.8
BMS-955176: Median Δ in HIV-1 RNA Over Time
Placebo5 mg10 mg20 mg40 mg80 mg120 mg
Me
dia
n Δ
in
HIV
-1 R
NA
F
rom
B
L (
log
10 c
/mL
)
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NA-ACCORD: Recent Abacavir Use and Risk of MI Retrospective analysis of pts in 7
clinical cohorts with recent ABC use from 1/1/1995 to 12/31/2010
“Recent” ABC initiation: prescribed within previous 6 mos
ABC initiators (n = 1948) vs non-ABC initiators (n = 14,785):
– “Full” study population: all ART users excluding persons on ABC at study entry
– “Restricted” population: ART-naive persons who initiated ART in the cohort
Endpoint of incident MIs: presence of clinical diagnosis or elevation of cardiac enzymes
– All MIs independently adjudicatedPalella F, et al. CROI 2015. Abstract 749LB. Reproduced with permission.
0.00 2.001.00 4.003.00
Full Study
Restricted Study
D:A:DReplication
1.95
1.33
Recent ABC use significant in restricted population and D:A:D replication
Association diminished after adjusting for additional CVD risk factors in multivariate analysis
Significant factors
– Both: age 60+ yrs, HTN, eGFR < 30, AIDS
– Full: smoking, DM
Adjusted HRs for MI in Those With Recent ABC Use
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A5260: Changes in Limb and Trunk Fat With INSTI vs PI/RTV First-line Regimens Metabolic substudy of A5257,
comparison of first-line TDF/FTC +
– RAL (n = 106)
– ATV/RTV (n = 109)
– DRV/RTV (n = 113)
Endpoints: change from BL to Wk 96 in peripheral fat, central adiposity, lean mass
– ATV/RTV vs DRV/RTV
– Combined PIs vs RAL
Trend toward greater % change in lean mass in ATV/RTV vs DRV/RTV
– Combined PIs similar to RAL
Similar changes in limb and trunk fat (SAT and VAT) among regimens
Greater gains in VAT and SAT in BL VL stratum HIV-1 RNA ≥ 100,000 c/mL vs < 100,000 c/mL, regardless of regimen
McComsey G, et al. CROI 2015. Abstract 140. Reproduced with permission.
ATV/RTV 31%RAL 33%DRV/RTV 29%
NATV/RTV 108 97RAL 105 95DRV/RTV 112 94
Wk 96BL
504030
2010
0
VAT Change
Mea
n %
Ch
an
ge
Fro
m
Bas
elin
e ATV/RTV vs DRV/RTV (P = .54)PI/RTV vs RAL (P = .72)
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Randomized Trial of Statin Therapy and Coronary Plaque Progression Randomized 12-mo trial in HIV+ pts
on stable ART with LDL-C < 130 and ≥ 1 coronary plaque
– Atorvastatin 20 mg ( to 40 mg at 3 mos) (n = 19) vs
– Placebo (n = 21)
Statin therapy reduced progression of coronary plaques
– Reduced overall plaque volume, including lipid-laden plaques
– Reduced high-risk morphology plaques
Statin therapy safe and well tolerated
Lo J, et al. CROI 2015. Abstract 136. Reproduced with permission.
Plaque Progression in Proximal Left Anterior Descending Coronary
Artery With Atorvastatin or Placebo
BL
12 mos
PlaceboAtorvastatin
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D:A:D: ARV Exposure and Risk of CKD
Retrospective analysis of pts with BL eGFR > 90/mL/min (N = 23,560)
– Evaluated cumulative exposure to TDF, ABC, ATV/RTV, LPV/RTV, other PIs and risk of CKD
– 210 pts developed CKD
Multivariate analysis: exposure to TDF, ATV/RTV, and LPV/RTV significantly associated with CKD development
– Risk greatly over 5 yrs
Association with TDF or LPV/RTV and CKD remains when excluding those who stopped drugs during or before study entry
When TDF exposure censored, CKD risk per yr of ATV/RTV or LPV/RTV exposure increased substantially
CKD risk with time after stopping TDF
CKD Risk by Yrs of ARV Exposure, IRR (95% CI)
Drug 1 Yr 2 Yrs 5 Yrs
TDF1.12 (1.06-1.18)
1.25 (1.12-1.39)
1.74 (1.33-2.27)
ATV/RTV
1.27 (1.18-1.36)
1.61 (1.40-1.84)
3.27(2.32-4.61)
LPV/RTV
1.16 (1.10-1.22)
1.35 (1.21-1.50)
2.11(1.62-2.75)Mocroft A, et al. CROI 2015. Abstract 142. Reproduced with permission.
Relationship Between Increasing Exposure to ARVS and CKD
1.80
1.60
1.40
1.20
1.00
0.00ATV/RTV LPV/RTV TDF
Univariate
Multivariate
On treatment
TDF censored
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ION-4: LDV/SOF for 12 Wks in GT1/4 HCV/HIV-Coinfected Pts Phase III open-label study in HIV
virologically suppressed HIV/HCV coinfected pts (N = 335)
– 20% with compensated cirrhosis
– n = 8 with HCV GT4
ART regimens
– TDF/FTC/EFV (n = 160)
– TDF/FTC + RAL (n = 146)
– TDF/FTC/RPV (n = 29)
HCV treatment experienced, 55%
– Previous HCV PI therapy: 29%
– n = 13 previously failed SOF + RBV
Very high rate of SVR12
– No difference in SVR rates based on HCV treatment experience or cirrhosis status
SV
R12
(%
)
96
0
20
40
60
80
95 97 96 94
Overall No Yes
n/N =321/335
142/150
100
179/185
258/268
63/67
No Yes
Naggie S, et al. CROI 2015. Abstract 152LB. Reproduced with permission.
SVR Rates According to BL Characteristics
CirrhosisPrevious HCV Tx
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ION-4: LDV/SOF Effective Across All Pt Demographic and Disease Subgroups
10 relapses all in black pts
No pt with HIV virologic rebound
No discontinuation of therapy due to adverse events
4 pts experienced increase in creatinine > 0.4 mg/dL
– 2 completed treatment without change in ART
– 1 pt changed TDF to new NRTI
– TDF dose reduced in 1 pt
Naggie S, et al. CROI 2015. Abstract 152LB. Reproduced with permission.
BlackNonblack
1a1b4
< 800,000≥ 800,000
< 30≥ 30
CCCTTT
TDF/FTC/EFVTDF/FTC + RALTDF/FTC/RPV
< 350≥ 350
HCV Genotype
Baseline HCV RNA (IU/mL)
Baseline BMI (kg/m2)
Race
IL28B
ARV Regimen
Baseline CD4 (cells/mm³)
Overall
60 70 80 90 100
SVR12, % (95% CI)
Statistically significant in multivariate analysis
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ION-4: Resistance Analysis and LDV/SOF Drug–Drug Interactions With bPIs Deep sequencing at BL
identified 67 (20%) pts with NS5A RAVs[1]
– 63 (94%) of these pts achieved SVR12
RAVs in NS5A found in 10/12 pts with virologic failure
No S282T mutation in NS5B found in any pt at BL or virologic failure
In drug–drug interaction studies with LDV/SOF and boosted PIs and TFV[2]
– LDV/SOF increases ATV, RTV, and TFV exposure
– ATV/RTV + TDF/FTC increases LDV
– DRV/RTV + TDF/FTC decreases SOF
Staggered administration did not mitigate interactions but interactions not deemed clinically relevant
1. Naggie S, et al. CROI 2015. Abstract 152LB. 2. German P, et al. CROI 2015. Abstract 82.
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ALLY-2: SOF + DCV in GT1-6 HCV/HIV-Coinfected Pts Phase III open-label study
– Non GT1 < 20% in each cohort; compensated cirrhosis < 50% overall; HIV-1 RNA < 50 c/mL and CD4+ ≥ 100 in pts on ART; CD4 ≥ 350 in pts not on ART
– ART allowed: PI/RTV, NRTIs, NNRTIs, INSTIs, MVC, ENF
Primary endpoint: SVR12 in GT1 naive pts treated for 12 wks
Wyles DL, et al. CROI 2015. Abstract 151LB.
Treatment-naive pts(N = 151)
SOF 400 mg QD + DCV 30/60/90* mg QD
(n = 101)
SOF 400 mg QD + DCV 30/60/90* mg QD
(n = 52)
Treatment-experienced pts(N = 52)
Wk 12
Pts followed to Wk 36
SOF 400 mg QD + DCV 30/60/90* mg QD
(n = 50)
Wk 8
*Standard dose of 60 mg adjusted for ART: 30 mg with RTV; 90 mg with NNRTIs except RPV.
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High SVR12 rates with 12 wks SOF + DCV
– Large decline in SVR rate with shortening to 8 wks
12-Wk 12-Wk8-Wk 12-Wk 12-Wk8-Wk
ALLY-2: Virologic Outcomes With SOF + DCV in HIV/HCV-Coinfected Pts
In 12-wk groups analyzed by GT, 100% with SVR12 except GT1a
– GT1a naive: 96%; exp’d: 97%
Similar SVR12 rates in pts with or without baseline NS5A RAVs
12 pts with relapse, 10 in 8-wk arm
– 1 in 8-wk arm had emergent NS5A RAVs
No NS5B RAVs at BL or time of failure
No discontinuation of therapy due to AEs
10 pts with HIV-1 RNA > 50 at EOT
– 8 with repeat testing; 7 with suppression without change in ART; 1 with HIV-1 RNA of 59; 2 LTFU
2 with HIV VF = HIV-1 RNA ≥ 400 c/mL
SV
R12
, %
96
0
20
40
60
80
98
76
97 98
n/N =80/83
43/44
100
31/41
98/101
51/52
76
38/50
Wyles DL, et al. CROI 2015. Abstract 151LB. Reproduced with permission.
Naive Exp’d Naive Exp’d
GT1 Overall
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Capsule Summaries of key data from the conference
CME-certified Expert Analysis module with faculty commentary on key studies presented in Seattle
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