July 20-25, 2014 Melbourne, Australia Highlights of AIDS 2014 CCO Official Conference Coverage of the 20th International AIDS Conference This program is supported by an educational grant from This program is supported by educational grants from Gilead Sciences and ViiV In partnership with
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Highlights of AIDS 2014 .CCO Official Conference Coverage of the 20th International AIDS Conference
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July 20-25, 2014Melbourne, Australia
Highlights of AIDS 2014 CCO Official Conference Coverageof the 20th International AIDS Conference
This program is supported by an educational grant from
This program is supported by educational grants from Gilead Sciences and ViiV
In partnership with
clinicaloptions.com/hivHighlights of AIDS 2014 clinicaloptions.com/hivHighlights of AIDS 2014
About These Slides
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Faculty
David A. Cooper, MD, DScDirector, Kirby InstituteUniversity of New South WalesSydney, Australia
Joel E. Gallant, MD, MPHAssociate Medical Director of Specialty ServicesSouthwest CARE CenterSanta Fe, New MexicoAdjunct Professor of MedicineDivision of Infectious DiseasesJohns Hopkins University School of MedicineBaltimore, Maryland
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Disclosures
David A. Cooper, MD, DSc, has disclosed that he has received consulting fees from Gilead Sciences, Janssen, Merck, and ViiV and funds for research support from AbbVie, Gilead Sciences, and Merck.
Joel E. Gallant, MD, MPH, has disclosed that he has received consulting fees from Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and Takara Bio and funds for research support from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Merck, Sangamo Biosciences, Vertex, and ViiV.
Antiretroviral Therapy
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IAS-USA: 2014 Recommended Regimens for First-line ART
*Please see notes section of slide for important caveats regarding certain agents and regimens.
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Randomized, double-blind, international phase III trial
Primary endpoint: HIV-RNA < 50 c/mL at Wk 48
TDF/FTC QD + DRV/RTV QD
MVC 150 mg QD + DRV/RTV QD
Treatment-naive HIV-infected
patients
Wk 48primary analysis
Stellbrink HJ, et al. AIDS 2014. Abstract MOAB0101.
MODERN: Maraviroc QD + Darunavir/RTV as First-line ART
TDF/FTC QD + DRV/RTV QD
MVC 150 mg QD + DRV/RTV QD
Phenotypic tropism assay
Genotypic tropism assay
Randomization of pts with CCR5-tropic HIV
clinicaloptions.com/hivHighlights of AIDS 2014 clinicaloptions.com/hivHighlights of AIDS 2014
MODERN: MVC QD + DRV/RTV Not Noninferior to TDF/FTC + DRV/RTV
HARNESS: suppressed pts switched from any ART to ATV/RTV + RAL had higher rates of virologic rebound vs those switched to ATV/RTV + TDF/FTC[2]
Similar rates of HIV-1 RNA suppression at Wk 48 by screening assay type
1. Stellbrink HJ, et al. AIDS 2014 Graphic used with permission. Abstract MOAB0101. 2. van Lunzen J, et al. AIDS 2014. Abstract LBPE19.
MVC + DRV/RTV (n = 396)
TDF/FTC + DRV/RTV (n = 401)
100
80
60
40
20
0
Wk
Pts
Wit
h H
IV-1
RN
A <
50
co
pie
s/m
L[1
]
BL 4 8 12 16 20 24 36 48
77.3%
86.8%
Adjusted treatment difference: -9.5% (95%% CI: -14.8% to -4.2%)
Assay Type
MVC + DRV/RTV(n = 396)
TDF/FTC + DRV/RTV(n = 401)
Phenotypic 74.4 87.0
Genotypic 80.7 86.5
Δ (95% CI) 6.9% (-1.3% to 15%)
NR
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OLE: Simplification to Dual ART With LPV/RTV + 3TC or FTC in Suppressed Pts Randomized, open-label phase III noninferiority trial
Primary endpoint: free of VF at Wk 48
HIV-infected patients with HIV-1 RNA < 50 c/mL;
on triple ART with LPV/RTV + 3TC or FTC + NRTI for 6 mos; no resistance to LPV/RTV or 3TC or FTC
(N = 239)
Lopinavir/Ritonavir 400/100 mg BID +Lamivudine or Emtricitabine
(n = 118)
Lopinavir/Ritonavir 400/100 mg BID +Lamivudine or Emtricitabine +
Investigator-selected NRTIs in FDC* (n = 121)
Wk 48primary analysis
Gatell J, et al. AIDS 2014. Abstract LBPE17.
*TDF/FTC: 60%; ABC/3TC: 28%; Other: 12%
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OLE: Switching Suppressed Pts to Dual ART Noninferior to Triple ART at Wk 48
New grade 3/4 AEs in 9 pts in each arm
Significantly greater increases in TC (P = .02), numerically greater increases in TG (P = .09) in dual-ART arm
Numerically greater decreases in creatinine in triple-ART arm
New lab abnormalities similar
VF in 3 pts in each arm
– 1 pt (dual-ART) tested for resistance; had K103N and M184V
SALT trial of switches in suppressed pts showed switch to ATV/RTV + 3TC noninferior to switch to ATV/RTV + 2 NRTIs[2]
Pat
ien
ts (
%)[1
]
91.5 90.9
Δ -0.6%(95% CI: -6.9% to 8.1%)
Dual ART (n = 118)
Triple ART (n = 121)
0
20
40
60
80
100
2.5 2.5 0.83.3
n =
Therapeutic Response*
VF D/C Due to AE
D/C for Other
Reasons
5.1 3.3
*HIV-1 RNA < 50 c/mL at Wk 48 (mITT).
1. Gatell J, et al. AIDS 2014. Abstract LBPE17. Graphic used with permission. 2. Perez-Molina JA, et al. AIDS 2014. Abstract LBPE18.
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SAILING Subanalysis: Activity of DTG in INSTI-Naive Pts With NRTI Resistance Post hoc analysis of SAILING: randomized, double-blind, active-
controlled phase III noninferiority trial
Treatment-experienced, INSTI-naive patients with
HIV-1 RNA ≥ 400 copies/mL and ≥ 2 class
resistance(N = 715)
Dolutegravir 50 mg QD +background regimen*
(n = 354)
Raltegravir 400 mg BID +background regimen*
(n = 361)
Wk 96
Stratified by number of fully active background agents, use of DRV,
screening HIV-1 RNA ≤ vs > 50,000 c/mL
*Background regimen contains 1-2 agents, at least 1 of which is fully active.
Current Analysis: Wk 48
Demarest J, et al. AIDS 2014. Abstract TUAB0104.
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SAILING: No Virologic Failure With DTG + NRTIs, Even If No Fully Active NRTIsPts With Protocol-Defined Virologic Failure at Wk 48, n/N (%)
DTG 50 mg QD(n = 354)
RAL 400 mg BID(n = 361)
Overall 21/354 (6) 45/361 (12)
Type of background regimenPI containingNRTI onlyOther
18/300 (6)0/32
3/22 (14)
36/305 (12)7/32 (22)22/24 (8)
Fully active NRTIs* in background regimen210Missing phenotype
0/160/120/10/3
3/194/13
----
Demarest J, et al. AIDS 2014. Abstract TUAB0104.
*Fully active based on PhenoSense assay.
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Canadian National Cohort: Switching After Suppression Associated With Risk of VF Retrospective analysis of correlates
of VF among suppressed pts who switched ART for reasons other than VF (N = 2807)
– Initiated first-line ART with ≥ 3 agents between 1/1/2005 and 6/30/2012
In multivariate model
– Switching ART associated with increased risk of VF (P < .001)
– Females and patients with IDU history at increased risk of VF with switch (P < .001)
Authors advocate closer follow-up of pts switching for nonvirologic reasons
– Switching may serve as marker for problems with adherence or tolerance of ART agents
Hull M, et al. AIDS 2014. Abstract TUAB0103. Table used with permission.
Factor Adj OR(95% CI)
P Value
ART switch 1.35 (1.18-1.53) < .001
Male sex 0.35 (0.21-0.58) < .001
IDU 2.85 (1.70-4.80) < .001
Age (per 10 yrs) 0.98 (0.71-1.35) .884
BL CD4+ count, per 100 cells/mm3 1.08 (0.93-1.26) .30
Initiated ART before vs after 2008
1.17 (0.70-1.93) .55
Province (ref. British Columbia) .260
Ontario Quebec
1.11 (0.63-1.95)1.33 (0.78-2.26)
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Resistance analysis of randomized, open-label, multicenter trial
LPV/RTV + RAL
(n = 270)
LPV/RTV + 2-3 NRTIs*(n = 271)
HIV-infected patients with confirmed VF
on NNRTI + 2 NRTIswith no previous PI
or INSTI use(N = 541)
Wk 96
*NRTIs selected by genotypic resistance test or by algorithm.
SECOND-LINE Subanalysis: Resistance to NRTIs and Risk of Virologic Failure
Primary analysis: LPV/RTV + RAL noninferior to LPV/RTV + 2-3 NRTIs after VF of initial NNRTI regimen
46% with high-level NRTI resistance at baseline by global genotypic sensitivity score
Risk of VF at Wk 96 in both treatment arms higher among pts with lower levels of NRTI resistance by gGSS
Boyd M, et al. AIDS 2014. Abstract TUAB0105LB. Graphic used with permission.
VF at Wk 96 by BL Resistance Level, %
LPV/RTV +2-3 NRTIs
LPV/RTV + RAL
High 9 14
Moderate 13 12
Low 43 38
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SECOND-LINE: Predictors of Virologic Failure at Wk 96 by Multivariate Analysis Risk of VF at Wk 96 higher among pts with lower levels of NRTI resistance by gGSS
Predictors of VF at Wk 96 Multivariate OR (95% CI) P Value
Adherence (Wk 4) All ART in last 7 days < All ART in last 7 days
1 (ref) 2.18 (1.07-4.47) .032
Adherence (Wk 48) All ART in last 7 days < All ART in last 7 days
1 (ref)3.43 (1.09-5.69) .03
Resistance by gGSS High Moderate Low
1 (ref) 1.03 (0.52-2.03) 4.73 (1.04-11.46) .002
Boyd M, et al. AIDS 2014. Abstract TUAB0105LB. Table used with permission.
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In modified analysis, no difference in rate of VF among those with consistent HIV-1 RNA < 20 vs those HIV-1 RNA < 20 c/mL and transient increases to 50 c/mL
– Transient HIV-1 RNA increases to > 200 significantly associated with VF (P = .0157)
– Trend toward increased risk of VF with blips between 50-200 copies/mL (P = .09)
VACH Cohort: HIV-1 RNA 20-50 c/mL Not Predictive of VF After Suppression to < 20 Retrospective analysis of Spanish
VACH cohort (N = 21,480 on ART)
Compared risk of virologic failure in
– Pts maintaining HIV-1 RNA < 20 c/mL vs
– Pts with transient increases (“blips”) of HIV-1 RNA to 20-50 c/mL
Analysis included pts with HIV-1 RNA < 50 c/mL on 2 determinations and HIV-1 RNA < 20 c/mL at least once
VF: one HIV-1 RNA > 200 followed by one of the following
– Second HIV-1 RNA > 200, censoring, change of treatment, or loss to follow-up
Teira R, et al. AIDS 2014. Abstract TUAB0102. Table used with permission.
Factors Predictive of VF
Variable RH 95% CI
Transient VL 20-50 vs consistent VL < 20
0.588 0.399-0.899
Nadir CD4+ count 0.998 0.997-0.999
MSM vs IDU 0.577 0.337-0.989
Time receiving effective ART (per yr)
0.916 0.853-0.983
Pre-Exposure Prophylaxis(PrEP)
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iPrEX OLE: Oral PrEP Reduces Incidence of HIV in MSM Open-label extension of iPrEX trial of daily TDF/FTC oral PrEP in MSM and
transgender women (N = 1603)
– Started PrEP at enrollment: 72%
– Started PrEP later: 6%
– Never started PrEP: 23%
PrEP uptake significantly higher among those reporting receptive anal intercourse without condoms (P = .003) or HSV coinfection (P = .03)
Evaluated HIV acquisition according to PrEP use, adherence, and risk behavior
HIV incidence decreased in those starting PrEP
– HR adjusted for sexual behavior: 0.51 (95% CI: 0.26-1.01)
Grant R, et al. AIDS 2014. Abstract TUAC0105LB.
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iPrEX OLE: 100% Adherence With Daily PrEP Not Required to Attain Full Benefit
TFV-DP: tenofovir diphosphate (measurable tenofovir in dried blood spots)
Grant R, et al. AIDS 2014. Abstract TUAC0105LB. Graphic used with permission.
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iPrEX OLE: HIV Infection Occurred During Periods of Nonadherence
Grant R, et al. AIDS 2014. Abstract TUAC0105LB. Graphic used with permission.
1.0
0.8
0.6
0.4
0.2
072 60 48 36 24 12 0 12 24 36 48 60
Control
ControlCase
Case
Wks PostinfectionWks Preinfection
3808
130622
164722
139624
148924
144126
133828
7687
386 266 171 44Control, n:Case, n:
Pro
po
rtio
n W
ith
TF
V-D
P
Det
ecte
d i
n D
ried
Blo
od
Sp
ots
First evidence of HIV infection
TFV-DP LLOQ TFV-DP ≥ 350 fmol/punch
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ANRS Ipergay: Detection of TFV in Plasma After On-Demand PrEP ANRS Ipergay: planned randomized,
placebo-controlled trial of event-driven PrEP vs placebo in MSM engaging in high-risk sex
Planned study population: 950 per arm
Event-driven PrEP:
2 tablets (TDF/FTC or placebo) 2-24 hrs before sex
1 tablet 24 hrs later
1 tablet 48 hrs later
Proof-of-concept of 129 pts measuring TFV and FTC in plasma after intermittent PrEP
Overall, TFV was detected in plasma in 86% of samples from pts in the TDF/FTC arm vs 4% from those in placebo arm
0
20
40
60
80
100
113 0
1071
1012
864
776
488
1610
56 57 51 56 49 52 42 44 37 40 22 26 8 8
100
8883
918582
4 6 5 50 02
52333404446 22323 8
Par
tici
pa
nts
(%
)
Fonsart J, et al. AIDS 2014. Abstract TUAC0103. Graphic used with permission.
Arm ns:N:
Month:
Comorbidities
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All time-updated variables
D:A:D: BMI Gain After ART Initiation and Increased Risk of Diabetes, CVD Analysis of D:A:D cohort including pts starting ART with BMI data and no DM or CVD
1 yr before starting ART (N = 9321)
– 70% with normal or low BMI (< 25) before starting ART
Diabetes risk ↑ by ~ 10%/BMI unit gain after ART initiation regardless of pre-ART BMI
Post-ART BMI gain associated with ↑ risk of CVD in middle 2 pre-ART BMI quartiles
1.6
1.4
1.0
0.8
1.2
0.6BMI Q1< 20.9
BMI Q220.9-23.0
BMI Q323.0-25.5
BMI Q4> 25.5
IRR
*P for effect modification in adjusted models: .011
Adjusted IRR for CVD per Unit Gain in BMI
1.6
1.4
1.0
0.8
1.2IR
R
All Patients*
Underweight< 18.5
Normal18.5-25
Obese> 30
Overweight25-30
Pre-ART BMIPre-ART BMI*P for effect modification in adjusted models: > .05
Adjusted IRR for DM per Unit Gain in BMI
Achhra AC, et al. AIDS 2014. Abstract WEAB0103. Graphics used with permission.
*
*
*
Adjusted for demographics All time-updated variablesAdjusted for demographics
HCV Treatment in HIV/HCV-Coinfected Patients
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