Highlights of AIDS 2014 .CCO Official Conference Coverage of the 20th International AIDS Conference

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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Faculty
David A. Cooper, MD, DSc
Director, Kirby Institute
University of New South Wales
Sydney, Australia
Joel E. Gallant, MD, MPH
Associate Medical Director of
Specialty Services
Southwest CARE Center
Santa Fe, New Mexico
Adjunct Professor of Medicine
Division of Infectious Diseases
Johns Hopkins University
School of Medicine
Baltimore, Maryland

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.

IAS-USA: 2014 Recommended Regimens
for First-line ART
Günthard HF, et al. JAMA. 2014;312:410-425.
Class Recommended Regimens*
NNRTI
 EFV/TDF/FTC
 EFV + ABC/3TC
 RPV/TDF/FTC
Boosted PI
 ATV/RTV + TDF/FTC
 ATV/RTV + ABC/3TC
 DRV/RTV + TDF/FTC
INSTI
 DTG + ABC/3TC
 DTG + TDF/FTC
 EVG/COBI/TDF/FTC
 RAL + TDF/FTC
*Please see notes section of slide for important caveats regarding certain agents and regimens.

 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 48
primary 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

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
PtsWithHIV-1RNA<50copies/mL[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

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 48
primary analysis
Gatell J, et al. AIDS 2014. Abstract LBPE17.
*TDF/FTC: 60%; ABC/3TC: 28%; Other: 12%

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]
Patients(%)[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 0.8
3.3
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.

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.

SAILING: No Virologic Failure With DTG +
NRTIs, Even If No Fully Active NRTIs
Pts 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 regimen
PI containing
NRTI only
Other
18/300 (6)
0/32
3/22 (14)
36/305 (12)
7/32 (22)
22/24 (8)
Fully active NRTIs* in background regimen
2
1
0
Missing phenotype
0/16
0/12
0/1
0/3
3/19
4/13
--
--
Demarest J, et al. AIDS 2014. Abstract TUAB0104.
*Fully active based on PhenoSense assay.

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)

 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 NRTIs
with 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

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
Race
 Asian
 White
 Hispanic
 Black
1 (ref)
2.28 (0.65-8.02)
3.13 (1.21-9.13)
3.49 (1.68-7.28)
NR
.007
Baseline VL, copies/mL
 ≤ 100,000
 > 100,000
1 (ref)
3.43 (1.70-6.94) < .001
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.

 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)

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.

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.
HIV Incidence and Drug Concentrations
5
4
3
2
1
0
150012501000700500350LLOQ0
Off PrEP
On PrEP
TFV-DP in fmol/punch
7 Tablets/Wk4-6 Tablets/Wk< 2 Tablets/Wk 2-3 Tablets/Wk
HIVIncidenceper
100Person-Yrs
Follow-up,%
Risk Reduction,%
95% Cl, %
26
44
-31 to 77
21
100
12
100
86 to 100 (combined)
12
84
21 to 99

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
0
72 60 48 36 24 12 0 12 24 36 48 60
Control
ControlCase
Case
Wks PostinfectionWks Preinfection
380
8
1306
22
1647
22
1396
24
1489
24
1441
26
1338
28
768
7
386 266 171 44Control, n:
Case, n:
ProportionWithTFV-DP
DetectedinDriedBloodSpots
First evidence of HIV infection
TFV-DP LLOQ
TFV-DP ≥ 350 fmol/punch

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
107
1
101
2
86
4
77
6
48
8
16
10
56 57 51 56 49 52 42 44 37 40 22 26 8 8
100
88
83
91
8582
4 6 5 5
0 02
5
2333404446 22323 8
Participants(%)
Fonsart J, et al. AIDS 2014. Abstract TUAC0103. Graphic used with permission.
Arm ns:
N:
Month:

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
0.6
BMI Q1
< 20.9
BMI Q2
20.9-23.0
BMI Q3
23.0-25.5
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
1.2
IRR
All
Patients*
Underweight
< 18.5
Normal
18.5-25
Obese
> 30
Overweight
25-30
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

TURQUOISE-I: ABT-450/RTV/Ombitasvir +
Dasabuvir + RBV in GT1 HCV/HIV Pts
 Open-label phase II/III trial
 Inclusion criteria: GT1; compensated cirrhosis (Child-Pugh A) allowed; DAA naive but
pegIFN naive or experienced; HIV-1 RNA < 40 c/mL on ATV or RAL regimen; CD4+
count ≥ 200 or %CD4+ ≥ 14%
 52% on ATV, 49% on RAL in 12-wk arm; 38% on ATV, 63% on RAL in 24-wk arm; 19%
with cirrhosis
 Primary endpoint: SVR12
ABT-450/RTV/Ombitasvir + Dasabuvir + RBV
(n = 32)
ABT-450/RTV/Ombitasvir +
Dasabuvir + RBV
(n = 31)
Wk 24
Sulkowski M, et al. AIDS 2014. Abstract MOAB0104LB.
ABT-450/RTV/ombitasvir 150/100/25 mg once daily; dasabuvir 250 mg twice daily; RBV 1000-1200
mg/day.
DAA-naive
HIV-infected pts with
GT1 HCV infection
(N = 63)
Wk 12

TURQUOISE-I: Efficacy Results
 Anemia in 12.9% of 12-wk arm and 9.4% of 24-wk arm; hyperbilirubinemia in
35.5% of 12-wk arm and 18.8% of 24-wk arm
12 wks (n = 31)
24 wks (n = 32)
Patients(%)
100 100
31/31 32/32
0
20
40
60
80
100 96.8 96.9
93.5
96.9
n = 31/3230/31 29/31
RVR (Wk 4) EOTR
(Wk 12 or 24)
SVR4 SVR12
93.5
29/31 31/32
Sulkowski M, et al. AIDS 2014. Abstract MOAB0104LB. Graphic used with permission.

PHOTON-2: Sofosbuvir + Ribavirin in
GT1-4 HCV Pts Coinfected With HIV
 Ongoing, nonrandomized, open-label phase III study
 Stable ART (HIV-1 RNA < 50 copies/mL for ≥ 8 wks before enrollment); CD4:
> 200 cells/mm3
if ART treated; > 500 cells/mm3
if ART naive
– 97% on ART: TDF/FTC, 100%; EFV: 25%; ATV/RTV: 17%; DRV/RTV: 21%; RAL: 23%; RPV: 5%
 20% of pts with compensated cirrhosis
 Primary endpoint: SVR12
Molina JM, et al. AIDS 2014. Abstract MOAB0105LB.
Wk 24
Sofosbuvir + Ribavirin
(n = 200)
(n = 55)
(n = 19)
Wk 12
Tx-naive GT1, 3, 4
Tx-naive GT2
Tx-exp’d GT2, 3
Sofosbuvir 400 mg QD; weight-based ribavirin 1000 or 1200 mg/day

PHOTON-2: SVR12 by Genotype and
Cirrhosis
 Absolute CD4+ cell count—but not CD4%—decreased, consistent with effect of RBV on
lymphocytes
Molina J-M, et al. AIDS 2014. Abstract MOAB0105LB. Graphic used with permission.
24 wks, noncirrhotic
24 wks, cirrhotic
12 wks, noncirrhotic
12 wks, cirrhotic
0
20
40
60
80
100
Total GT1a GT1b Naive
GT1 Naive
PatientsWithSVR(%)
Exp’d Naive Exp’d Naive
GT2 GT3 GT4
89
100 100 100
78
9291
75
83
8888
65
87
62
100
75
84/
95
11/
17
76/
87
8/
13
7/
7
3/
4
16/
18
3/
4
49/
54
1/
1
2/
2
3/
3
24/
26
18/
23
19/
23
7/
8

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