IAS 2015.8th IAS Conference on HIV Pathogenesis, Treatment and Prevention

July 19-22, 2015
Vancouver, Canada
Highlights of IAS 2015
CCO Official Conference Coverage
of the 8th IAS Conference on HIV Pathogenesis, Treatment,
and Prevention*
*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 independent educational grant from
Bristol-Myers Squibb, Gilead Sciences, Merck, and ViiV.

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Faculty
Andrew Carr, MBBS, MD,
FRACP, FRCPA
Professor of Medicine
University of New South Wales
Director
HIV, Immunology, and Infectious
Disease Unit
St Vincent's Hospital
Sydney, Australia
Joel E. Gallant, MD, MPH
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
Anton L. Pozniak, MD, FRCP
Consultant Physician
Director of HIV Services
Department of HIV and Genitourinary
Medicine
Chelsea and Westminster Hospital
NHS Foundation Trust
London, United Kingdom

Disclosures
Andrew Carr, MBBS, MD, FRACP, FRCPA, has disclosed that he has
received consulting fees, funds for research support, and fees for non-
CME/CE services from Gilead Sciences, MSD, and ViiV and funds for
research support from Pfizer.
Joel E. Gallant, MD, MPH, has disclosed that he has received consulting
fees and funds for research support from Bristol-Myers Squibb, Gilead
Sciences, Janssen Therapeutics, Merck, and ViiV Healthcare and funds
for research support from AbbVie and Sangamo.
Anton L. Pozniak, MD, FRCP, has disclosed that he has received
consulting fees and funds for research support from Bristol-Myers
Squibb, Gilead Sciences, Janssen Therapeutics, Merck, and ViiV.

UNAIDS: 90-90-90 Treatment Targets
Levi J, et al. IAS 2015. Abstract MOAD0102. Reproduced with permission.
100
80
60
40
20
0
HIV Positive
People
Diagnosed On ART Viral
Suppression
36.9
million 33.2
million 29.5
million 26.9
million
Target 1:
90% of HIV+
people
diagnosed
Target 2:
90% of
diagnosed
people on ART
Target 3:
90% of people on
ART with HIV-1
RNA suppression
90%
81%
73%
People(%)

UNAIDS: 90-90-90 Global Estimated Gaps
100
80
60
40
20
0
HIV Positive
People
Diagnosed On ART Viral
Suppression*
36.9
million
19.8
million
15.0
million 11.6
million
Breakpoint 1:
13.4 million
undiagnosed Breakpoint 2:
14.9 million
not treated
Breakpoint 3:
15.3 million
not virally
suppressed
53%
41%
32%
Levi J, et al. IAS 2015. Abstract MOAD0102. Reproduced with permission.
*HIV-1 RNA < 1000 copies/mL.
People(%)

START: Immediate vs Deferred Therapy
for Asymptomatic, ART-Naive Pts
Immediate ART
ART initiated immediately
following randomization
(n = 2326)
INSIGHT START Study Group. N Engl J Med. 2015;[Epub ahead of print]. Lundgren J, et al. IAS 2015. Abstract
MOSY0302.
Deferred ART
Deferred until CD4+ cell count ≤ 350 cells/mm3
,
AIDS, or event requiring ART
(n = 2359)
HIV-positive, ART-naive
adults with CD4+ cell
count > 500 cells/mm3
(N = 4685)
Study closed by DSMB
following interim analysis

START: 57% Reduced Risk of Serious
Events or Death With Immediate ART
 4.1% vs 1.8% in deferred vs immediate arms experienced serious AIDS or
non-AIDS–related event or death (HR: 0.43; 95% CI: 0.30-0.62; P < .001)
10
8
6
4
2
0
CumulativePercentWithEvent
0 6 12 18 24 30 36 42 48 54 60
Mo
Deferred ART
Immediate ART
INSIGHT START Group. N Engl J Med. 2015;[Epub ahead of print]. Lundgren J, et al. IAS 2015. Abstract MOSY0302.
Reproduced with permission.

START: Primary Endpoint Components
With Immediate vs Deferred ART
Endpoint
Immediate ART
(n = 2326)
Deferred ART
(n = 2359) HR
(95% CI)
P Value
N Rate/100 PY N Rate/100 PY
Serious AIDS-related event 14 0.20 50 0.72
0.28
(0.15-0.50)
< .001
Serious non-AIDS–related event 29 0.42 47 0.67
0.61
(0.38-0.97)
.04
All-cause death 12 0.17 21 0.30
0.58
(0.28-1.17)
.13
Tuberculosis 6 0.09 20 0.28
0.29
(0.12-0.73)
.008
Kaposi’s sarcoma 1 0.01 11 0.16
0.09
(0.01-0.71)
.02
Malignant lymphoma 3 0.04 10 0.14
0.30
(0.08-1.10)
.07
Non-AIDS–defining cancer 9 0.13 18 0.26
0.50
(0.22-1.11)
.09
CVD 12 0.17 14 0.20
0.84
(0.39-1.81)
.65

START: Cancer Events With Immediate vs
Deferred ART
Cancer Event, n
Immediate
ART
(n = 2326)
Deferred
ART
(n = 2359)
Total 14 39
Kaposi’s sarcoma 1 11
Lymphoma, NHL + HL 3 10
Prostate cancer 2 3
Lung cancer 2 2
Anal cancer 1 2
Cervical or testis
cancer
1 2
Other types* 4 9
Time to Cancer Event
10
8
6
4
2
0
Cumulative%WithEvent
0 12 24 36 48 60
Mo
*Immediate ART: squamous cell carcinoma, plasma cell myeloma, bladder cancer, fibrosarcoma.
Deferred ART: gastric adenocarcinoma, breast cancer, ureteric cancer, malignant melanoma, myeloid
leukemia, thyroid cancer, leiomyosarcoma, liver cancer, squamous cell carcinoma of head and neck.
Deferred ART
Immediate ART
Rate/100 PY: immediate, 0.20; deferred, 0.56
(HR: 0.36; 95% CI: 0.19-0.66; P = .001)

START: Primary Endpoint Events by
Latest CD4+ Cell Count
Latest CD4+ count > 500 cells/mm3
Immediate
ART
Deferred
ART
Primary
events, %
(n/N)
88
(37/42)
59
(57/96)
Rate/100
PY
0.6 1.1
Immediate ART Deferred ART
PercentofFollow-upTime
Latest CD4+ Cell Count (cells/mm3
)
60
50
40
30
20
10
0
2
(4.7)
No. of Pts With Events
(Rates/100 PY)
No. of Pts With Events
(Rates/100 PY)
3
(0.8)
6
(0.4)
11
(0.6)
20
(0.6)
5
(1.8)
34
(2.0)
34
(1.5)
9
(0.6)
14
(1.1)
<350350-499500-649650-799
≥800
<350350-499500-649650-799
≥800

TEMPRANO: Immediate or Deferred ART
Initiation ± IPT for African Pts
 Randomized, controlled, unblinded, multicenter (Ivory Coast), 2 x 2 factorial
Pts with HIV infection
and CD4+ cell count
< 800 cells/mm3
who did not meet
WHO criteria for
initiating ART*
(N = 2056)
Immediate ART†
(n = 515)
Immediate ART†
+ IPT‡
(n = 518)
Deferred ART§
(n = 511)
Deferred ART§
+ IPT‡
(n = 512)
*WHO criteria evolved during the study (updates 2006, 2010, 2013). †
ART initiated immediately following
randomization. ‡
IPT = 300 mg daily isoniazid initiated 1 mo after enrollment and terminated 7 mos after
enrollment. §
Deferred until meeting WHO criteria for initiating ART.
TEMPRANO ANRS 12136 Study Group. N Engl J Med. 2015;[Epub ahead of print].
 Pts in the treatment arms well matched at baseline
– First-line ART primarily EFV + TDF/FTC (68% to 71%) or LPV/RTV + TDF/FTC
(22% to 24%)
 Median duration of follow-up: 29.9 mos

TEMPRANO: Immediate vs Deferred ART
Initiation and IPT Delivery for African Pts
TEMPRANO ANRS 12136 Study Group. N Engl J Med. 2015;[Epub ahead of print].
Mos From Randomization
CumulativeProbability
ofDeathorSevere
HIV-RelatedIllness(%)
25
20
15
10
5
0
0 6 12 18 24 30
Deferred ART
Deferred ART + IPT
Immediate ART
Immediate ART + IPT
30-Mo Probability, %
14.1
8.8
7.4
5.7

HPTN 052: ART for Prevention of HIV
Transmission in Serodiscordant Couples
 International, randomized, controlled trial
Stable, healthy, sexually
active, HIV-discordant
couples with 350-550
CD4+ cells/mm3
(N = 1763 couples)
Early ART Arm
Initiate ART immediately
(n = 886 couples)
Delayed ART Arm
Initiate ART at CD4+ cell count
≤ 250 cells/mm3
or at development of
AIDS-defining illness
(n = 877 couples)
 Participants informed of interim results beginning May 2011; ART offered to all index
participants in delayed ART arm; study continued until May 2015 to determine durability
of HIV transmission prevention
 84% of pts in delayed ART arm had initiated ART at Yr 1; 98% of pts had initiated ART
prior to study closure
Cohen MS, et al. IAS 2015. Abstract MOAC0101LB.

 No linked HIV transmissions observed when index participant stably suppressed on ART
HPTN 052: Partner Infections With Early vs
Delayed ART
 8 linked HIV infections diagnosed after seropositive pt started ART
– 4 infections likely occurred before, or soon after, ART initiation, and 4 infections occurred after
ART failure in seropositive pt
 Unlinked partner infection rates similar between study arms
Cohen MS, et al. IAS 2015. Abstract MOAC0101LB.
April 2005 - May 2011 May 2011 - May 2015
Overall
(April 2005 - May 2015)
Partner
Infections, n
(rate/100 PY)
Early
(1751 PY
F/U)
Delayed
(1731 PY F/U)
Early
(2563 PY F/U)
Delayed
(2449 PY F/U)
Early
(4314 PY F/U)
Delayed
(4180 PY F/U)
All 4 (0.23) 42 (2.43) 15 (0.59) 17 (0.69) 19 (0.44) 59 (1.41)
Linked 1 (0.06) 36 (2.08) 2 (0.08) 7 (0.29) 3 (0.07) 43 (1.03)
Risk Reduction With
Early ART, %
All infections 91 -- 14 -- 69 --
Linked
infections 97 -- 72 -- 93 --

 International, randomized, open-label phase II trial; results reported from
Harlem and Bangkok cohorts
HPTN 067/ADAPT: PrEP for MSM/TGW
Mannheimer S, et al. IAS 2015. Abstract MOAC0305LB.
Daily PrEP
1 dose daily
Time-Driven PrEP†
1 dose twice weekly +
1 dose after sex
HIV-negative
MSM and
TGW*
Event-Driven PrEP†
1 dose before and
1 dose after sex
Lead-in period
of directly
observed
therapy
Final
study
visit
TDF/FTC PrEP given at standard dose and dispensed using an electronic monitoring device.
Adherence and sexual risk behavior assessed by weekly interview conducted by phone or in person.
*Other inclusion criteria: reported anal intercourse and ≥ 1 other risk factor for HIV infection in last 6 mos;
creatinine clearance > 70 mL/min.
†
Participants instructed to take no more than 2 doses daily or 7 doses/wk.
Wk 34Wk 30Wk 0 Wk 6

 179 MSM or TGW randomized
– Daily PrEP, n = 59
– Time-driven PrEP, n = 60
– Event-driven PrEP, n = 60
 Baseline characteristics: median
age 30 yrs, 98% MSM, 70% black
 HIV seroconversion seen in 2 pts
– Both pts had low or undetectable
TDF in dried blood spots/plasma
at study visits
HPTN 067/ADAPT: Harlem Cohort
Comparison of PrEP Strategies
Mannheimer S, et al. IAS 2015. Abstract MOAC0305LB. Reproduced with permission.
*P = .001 vs daily. †
P = .47 vs event driven.
Complete coverage: taking ≥ 1 PrEP dose within 4 days before sex and ≥ 1 dose within 24 hrs after sex.
66
47*†
52*
100
80
60
40
20
0
CompleteCoverage(%)
Daily
Time driven
Event driven
Coverage of Sex Acts
According to PrEP Strategy

 Adherence significantly higher in daily dosing arm vs time-driven or event-driven arms
(65% vs 46% vs 41%, respectively; P < .0001 for both comparisons)
 Adherence did not differ significantly between the 2 nondaily dosing arms (P = .16)
TFV in Dried Blood SpotsDoses Required vs Taken
HPTN 067/ADAPT: Adherence to PrEP
Strategies in Harlem Cohort
Mannheimer S, et al. IAS 2015. Abstract MOAC0305LB. Reproduced with permission.
Doses required: P < .0001 for all strategy-type comparisons
Doses taken: P < .0001 for daily vs time-driven PrEP and event-
driven vs daily PrEP; P = .33 when comparing nondaily dosing
arms
Low level: detectable to ≤ 350 fmol
High level: > 350 fmol
P = .07 for daily vs time-driven PrEP
P = .01 for daily vs event-driven PrEP
P = .36 for time-driven vs event-driven PrEP
8249
7K
5K
3K
1K
0
Daily Time
Driven
Event
Driven
5526
3674
2468 25722356
Required tablets
Tablets taken
NumberofTablets
9K
80
60
40
20
0
100
%ofPtsReportingSex
inLast7Days(Wk30)
Undetectable
Low level
Higher level
Daily Time
Driven
Event
Driven
50
22
28
39
17
44
56
28
17

HPTN 067/ADAPT: Bangkok Cohort
Comparison of PrEP Strategies
 178 MSM or TGW randomized
– Daily PrEP, n = 60
– Time-driven PrEP, n = 59
– Event-driven PrEP, n = 59
 Baseline characteristics:
median age 31 yrs, 99% MSM,
100% Asian
Holtz TH, et al. IAS 2015. Abstract MOAC0306LB.
*P = .02 vs daily arm, P = .04 vs time driven
arm. Complete coverage defined as taking
≥ 1 PrEP dose within 4 days before sex and
≥ 1 dose within 24 hrs after sex.
100
80
60
40
20
0
85 84
74*
Daily
Time driven
Event driven
Coverage of Sex Acts
According to PrEP Strategy
CompleteCoverage(%)

HPTN 067/ADAPT: Adherence to PrEP
Strategies in Bangkok Cohort
 Doses required vs doses taken  Significantly higher adherence with
daily (85%) and time-driven (79%)
vs event-driven (65%) PrEP
(P < .001)
 Detectable levels of TFV in PBMCs
were found in 91%, 95%, and 86%
of pts in the daily, time-driven, and
event-driven arms, respectively, at
Wk 30 among participants reporting
sex in past
7 days
 HIV seroconversions observed in 2
pts during prerandomization directly
observed dosing phase
– Both associated with undetectable
or low levels of FTC or TFV in
plasma/PBMCs
Doses required and taken: P < .001 for all
strategy-type comparisons.
Holtz TH, et al. IAS 2015. Abstract MOAC0306LB.
NumberofTablets
Time
Driven
Event
Driven
1928 2157
4121
3713
9420
8285 Required tablets
Tablets reported taken
Daily
10K
8K
6K
4K
2K
0

PrEP Demo: Implementation of Daily PrEP
by US MSM/TGW
 Prospective, open-label, cohort study conducted in 3 US STD or community-
based clinics in San Francisco, Miami, and Washington, DC (N = 557)
– Enrolled HIV-negative MSM (98%) and TGW (1.3%) who met behavioral risk
criteria; participants offered daily TDF/FTC as PrEP for up to 48 wks
 Retention rates declined from 93% at Mo 1 to 78% at Mo 12
– Participants with prior PrEP knowledge and those who reported condomless
receptive anal sex at baseline had higher retention rates
 63% of participants had protective TFV DBS levels at all study visits
(consistent with ≥ 4 doses/wk)
– Miami location, black race, fewer condomless anal sex partners, and unstable
housing were factors associated with lower rates of protective TFV DBS levels
 HIV incidence rates low at 0.43/100 PY (95% CI: 0.05-1.54)
Liu A, et al. IAS 2015. Abstract TUAC0202.

ATN 110: TDF/FTC PrEP For Young US
MSM
 Prospective, open-label, multicenter study
Hosek S, et al. IAS 2015. Abstract TUAC0204LB.
Behavioral
Intervention
HIV-negative 18- to
22-yr-old MSM at high
risk for HIV contraction
(N = 200)
Wk 0: PrEP Dispensed
TDF/FTC PrEP
Wk 48
 Baseline: mean age 20.2 yrs; 53% black, 21% white, 17%
Latino, 7% other/mixed race, 2% Asian/pacific islander
 4 seroconversions through Wk 48; each pt had undetectable
TFV levels
– HIV incidence: 3.29/100 PY
– No drug resistance detected
Behavioral intervention: Many Men, Many Voices (3MV) or Personalized Cognitive Counseling (PCC).

ATN 110: TDF/FTC PrEP for Young US
MSM
 Adherence decreased from baseline to Wk 48
– Undetectable levels of DBS TFV occurred in < 10% of pts at Wk 4 and
~ 30% of pts at Wk 48
 Black pts had decreased adherence compared with other races
Hosek S, et al. IAS 2015. Abstract TUAC0204LB. Reproduced with permission.
1200
1000
800
600
4+ doses
400
200
0
LevelsofTFVinDBS
(fmol/spot)
4 8 12 24 36 48
Overall
White
Latino
Mixed
Black
4+ doses
Wks

 International, randomized, open-label phase IV trial conducted in
resource-limited settings
REMEMBER: Benefits of Empiric TB
Treatment vs IPT at ART Initiation
 Pts in the treatment arms well-matched at baseline
– Pts with CD4+ cell count < 25 c/mm3
: empiric TB arm, 63%; IPT arm, 61%
Hosseinipour M, et al. IAS 2015. Abstract MOAB0205LB.
Preemptive TB Treatment
ART + Empiric TB Treatment*†
(n = 424)
Isoniazid at TB Diagnosis
ART + IPT*‡
(n = 426)
HIV-infected pts
with CD4+ cell count
< 50 cells/mm3
and no active TB
(N = 850)
*Empiric treatment consisted of fixed-dose isoniazid, rifampicin, pyrazinamide, and ethambutol for 8 wks,
followed by fixed-dose isoniazid and rifampin for 16 wks. †
ART consisted of EFV + TDF/FTC or 2 NRTIs
available locally. ‡
IPT consisted of isoniazid 300 mg QD for 24 wks.

 Empiric TB treatment had no differential impact on risk of death or unknown
status at 24 wks of follow-up vs IPT
 Time to death or unknown status did not differ by treatment strategy
 IPT treatment was associated with reduced time to confirmed or probable TB
(P = .01) vs empiric TB treatment
 Verified TB cases more frequent in empiric TB treatment arm vs IPT arm
(33/424 vs 19/426, respectively)
REMEMBER: Key Results
Absolute risk difference: -0.06% (95% CI: -3.05% to 2.94%; P = .97)
Hosseinipour M, et al. IAS 2015. Abstract MOAB0205LB.
Primary Endpoint, n (%)
ART + Empiric TB Treatment
(n = 424)
ART + IPT
(n = 426)
Death 20 (4.8) 22 (5.2)
Unknown status 2 (< 0.5) 0 (0)
All primary endpoints 22 (5.3) 22 (5.2)

 International, randomized, double-blind phase III trial
 Pts generally well matched at baseline
– Pts with HIV-1 RNA > 100,000 copies/mL: EVG/COBI/TDF/FTC arm,
24%; ATV/RTV + TDF/FTC arm, 25%
WAVES: EVG/COBI/TDF/FTC vs ATV/RTV
+ TDF/FTC in Treatment-Naive Women
Squires K, et al. IAS 2015. Abstract MOLBPE08.
EVG/COBI/TDF/FTC QD +
Placebos for ATV, RTV, and TDF/FTC QD
(n = 289)
ATV/RTV + TDF/FTC QD +
Placebo for EVG/COBI/TDF/FTC QD
(n = 286)
HIV-infected women
with HIV-1 RNA
≥ 500 copies/mL;
no previous ART;
and eGFR ≥ 70 mL/min
(N = 575)
Wk 48
Open-
label
extensio
n
ATV 300 mg; RTV 100 mg; TDF/FTC 300/200 mg; EVG/COBI/TDF/FTC 150/150/300/200 mg

WAVES: Key Results
 EVG/COBI/FTC/TDF superior to
ATV/RTV + TDF/FTC
– Overall treatment difference
6.5% (95% CI: 0.4%-12.6%)
 No significant differences between
arms in change from BL for eGFR,
spine or hip BMD, LDL or HDL
cholesterol, total cholesterol to HDL
ratio, or triglycerides
 Significantly greater increase in
total cholesterol with
EVG/COBI/TDF/FTC
 Lower rate of discontinuations due
to AEs with EVG/COBI/TDF/FTC vs
ATV/RTV + TDF/FTC (2.4% vs
7.0%)
Squires K, et al. IAS 2015. Abstract MOLBPE08. Reproduced with permission.
HIV-1RNA<50c/mL(%)
100
80
60
40
20
0
Overall ≤ 100,000 > 100,000
HIV-1 RNA (copies/mL)
EVG/COBI/TDF/FTC ATV/RTV + TDF/FTC
87
81
86
82
90
78
n = 289 286 220 214 69 72
Emergent Resistance
EVG/COBI/FTC/TDF
(n = 289)
ATV/RTV + TDF/FTC
(n = 286)
Resistance analysis
population 19 21
Developed resistance
mutations to study drugs 0 3

 Multicenter, randomized, open-label trial[1]
– Pts were Thai adults with baseline body weight of 59 kg (both arms)
– Dose of ATV/RTV 200/100 mg has shown adequate pharmacokinetics in
Thai pts[2]
LASA: ATV/RTV 200/100 mg vs 300/100 mg
1. Bunupuradah T, et al. IAS 2015. Abstract TUAB0101.
2. Avihingsanon A, et al. Clin Pharmacol Ther. 2009;85:402-408.
Thai pts with HIV-1 RNA
< 50 copies/mL (≥ 12
mos) on boosted PI
regimen for ≥ 3 mos
(N = 550*)
ATV/RTV 200/100 mg QD + 2 NRTIs
(n = 273)
ATV/RTV 300/100 mg QD + 2 NRTIs
(n = 277)
Stratified by site and use
of tenofovir and indinavir
Treatment
Wk 48
*ITT/NC = F population.

LASA: Key Results
 Higher rate of discontinuations with ATV/RTV 300/100 mg vs ATV/RTV 200/100 mg
(7.6% vs 2.6%; P = .01)
‒ ATV/RTV 300/100 mg associated with significantly higher mean total bilirubin and percentage
of pts experiencing grade 3/4 hyperbilirubinemia (P < .001)
 Estimated that treating 20,000 Thai HIV cases with ATV/RTV 200/100 mg instead of
300/100 mg would lead to a 5-yr savings of US$58 million (factoring in a 10% increase
in cases/yr)
‒ Note: PK analysis has shown that the median AUC is 58% higher in Thai pts vs white pts at a
dose of ATV/RTV 300/100 mg[2]
HIV-1RNA<50
cells/mL(%)
P = .03
NC = F
92
86
ATV/RTV 300/100
mg
ATV/RTV 200/100
mg
Difference in % Pts With HIV-1 RNA < 50 copies/mL
Favors ATV/RTV
300/100 mg
Favors ATV/RTV
200/100 mg
P = .03
NC = F
-10 0 10
1. Bunupuradah T, et al. IAS 2015. Abstract TUAB0101. 2. Avihingsanon A et al. Clin Pharmacol Ther. 2009; 85:402-408.

 Randomized, active-controlled, open-label study
 Primary endpoint: proportion of pts with HIV-1 RNA < 50 copies/mL
after 48 wks of treatment
Switching From TDF- to TAF-Based
Regimens in Virologically Suppressed Pts
Mills A, et al. IAS 2015. Abstract TUAB0102.
Pts with HIV-1 RNA < 50
copies/mL (≥ 96 wks)
and eGFR > 50 mL/min
on stable TDF-based
regimen for ≥ 48 wks
(N = 1436)
Switch to EVG/COBI/FTC/TAF QD*
(n = 959)
Continue previous TDF-based regimen†
(n = 477)
Primary Endpoint
Wk 48
*EVG/COBI/FTC/TAF (150/150/200/10 mg). †
Previous TDF-based regimens: EVG/COBI/FTC/TDF
(n = 459), EFV/TDF/FTC (n = 376), ATV/(COBI or RTV) + TDF/FTC (n = 601).
Continue
through
Wk 96

Switching From TDF- to TAF-Based
Regimens: Virologic Outcomes
Mills A, et al. IAS 2015. Abstract TUAB0102. Reproduced with permission.
100
80
60
40
20
0
Wk48HIV-1RNA<50c/mL(%)
All Prior
Regimens
Prior
EFV/TDF/FTC
Prior
Boosted
ATV + TDF/FTC
Prior
EVG/COBI/
FTC/TDF
EVG/COBI/FTC/TAF TDF-based regimenPrimary Endpoint
P < .001 P = .02 P = .02 P = NS
97 93 96
90
97
92
98 97
932/
959
444/
477
241/
251
112/
125
390/
402
183/
199
301/
306
149/
153n/N =

Switching From TDF- to TAF-based
Regimens: Renal and Bone Outcomes
 Hip BMD was similarly increased for pts treated with TAF
regimen (P < .001)
Mills A, et al. IAS 2015. Abstract TUAB0102. Reproduced with permission.
Regimen
Renal Events Leading to
Discontinuation
EVG/COBI/
FTC/TAF
(n = 959)
 Acute renal failure
 Interstitial nephritis
TDF-based
regimen
(n = 477)
 Chronic kidney disease
 Elevated serum creatinine
 Fanconi syndrome (mild
jaundice)
 Increased creatinine
 Nephritic colic
(nephrolithiasis)
4
3
2
1
0
-1
-2
-3
Median%Change
inSpineBMD(Q1,Q3)
Baseline Wk 24
EVG/COBI/FTC/TAF
TDF-based regimen
Wk 48
1.79
-0.28
P < .001

Switching Pts With HIV/HBV Coinfection to
a TAF-Based Regimen
 By Wk 48, 2/70 (3%) pts lost HBsAg/gained HBsAb; 2/30 (7%) pts had lost HBeAg; 1/30 (3%) pts
gained HBeAb
 Significant improvement in median Wk 48 FibroTest score with switch (-.04; P = .018)
Gallant J, et al. IAS 2015. Abstract WELBPE13. Reproduced with permission.
Pts(%)
94 92
Wk 24
Wk 48
100
80
60
40
20
0
HBV DNA < 29 IU/mL
86 92
 International, multicenter, single-arm, open-label phase IIIb trial (N = 72)
– Pts with virologically suppressed HIV infection on any regimen, chronic HBV
coinfection, and eGFR > 50 mL/min switched to EVG/COBI/FTC/TAF for 48 Wks
HIV-1 RNA < 50 c/mL
100
80
60
40
20
0

 Multicenter, open-label phase III trial
GS-112: Switching to a TAF-Based
Regimen in Pts With Renal Impairment
Gupta S, et al. IAS 2015. Abstract TUAB0103.
Virologically suppressed,
HIV-positive pts with
mild-moderate renal
impairment (stable
eGFRCG [30-69 mL/min])
(N = 242)
TDF-Based ART
(n = 158)
Non-TDF–Based ART
(n = 84)
EVG/COBI/FTC/TAF
(N = 242)
Wk 96
PI NNRTI INSTI
CCR5
Antag.
TDF ABC
Other
NRTI
No
NRTI
ART use,% 44 42 24 3 65 22 7 5
Wk 48Wk 24

GS-112: Key Results
Change in eGFR From
Baseline to Wk 48
Changes in Spinal BMD From
Baseline to Wk 48
Gupta S, et al. IAS 2015. Abstract TUAB0103. Reproduced with permission.
TDF Non-TDF
MedianChange
FromBaseline
10
0
-10
+0.2
-1.8 -1.5
-2.7*
Baseline: 58 53 56 50
eGFRCG
mL/min
eGFRCKD-EPI Cr
mL/min/1.73 m2
*P < .05
TDF Non-TDF
*P < .05
4
2
0
-2
Mean%Change
SpineBMD
2.95*
0.99
Baseline Wk 24 Wk 48

P007: DOR + TDF/FTC vs EFV + TDF/FTC
in ART-Naive Pts Infected With HIV
 Double-blind, randomized, 2-part study
Gatell JM, et al. IAS 2015. Abstract TUAB0104.
ART-naive, HIV-positive pts
with HIV-1 RNA ≥ 1000
copies/mL and CD4+ cell
count ≥ 100 cells/mm3
(N = 216*)
Doravirine†
+ TDF/FTC
(n = 108)
Efavirenz‡
+ TDF/FTC*
(n = 108)
*Combined pts from 2 study parts: Part 1 was a dose-finding study (n = 84) and Part 2 enrolled additional
pts with the current dosing schema (n = 132).
†
Doravirine dosed at 100 mg QD.
‡
Efavirenz dosed at 600 mg QD.
§
Wk 24 results reported.
Pts were stratified by HIV-1 RNA
≤ or > 100,000 copies/mL
Wk 96§

P007: Key Results
 Most virologic failure was due to low-level viremia
– Virologic failure, HIV-1 RNA ≥ 40 copies/mL: DOR, 15.7%; EFV, 10.2%
– Virologic failure, HIV-1 RNA ≥ 200 copies/mL: DOR, 3.7%; EFV, 0.9%
 Resistance testing was performed in 1 pt in each arm who failed treatment; no NRTI or
NNRTI mutations detected
Gatell JM, et al. IAS 2015. Abstract TUAB0104.
Pts With HIV-1 RNA
< 40 c/mL, %*
DOR +
TDF/FTC
(n = 108)
EFV +
TDF/FTC
(n = 108)
Wk 8 27.8 26.9
Wk 16 63.6 57.5
Wk 24 72.2 73.1
Baseline HIV-1 RNA
≤ 100,000 c/mL (n/N)†
83.3
(55/66)
85.7
(54/63)
Baseline HIV-1 RNA
> 100,000 c/mL (n/N)†
60.5
(23/38)
65.8
(25/38)
*NC = F approach.
†
Observed failure approach.
Event, %
DOR +
TDF/FTC
(N = 108)
EFV +
TDF/FTC
(N = 108)
One or more AE 75.9 84.3
Serious AE 0.9 4.6
Discontinued due to
AE
0.9 5.6
Drug-related AE 27.8 55.6
Pts with ≥ 1 CNS
event
26.9 46.3

 Prospective, observational study
Comparison of Single- and Multiple-Tablet
Regimens in ART-Naive Pts
Gatell JM, et al. IAS 2015. Abstract TUPEB264.
EFV/TDF/FTC Single-Tablet Regimen
(n = 759)
EFV + TDF + FTC Multitablet Regimen*
(n = 483)
Other Multitablet Regimen
(n = 1531)
ART-naive pts assigned
at physician’s discretion
to the noted regimens
(N = 2773)
Baseline Characteristics EFV/TDF/FTC STR EFV/TDF/FTC MTR Other MTR
Age, media (IQR) 37 (31-44) 37 (31-44) 37 (30-44)
Male, % 89 84 81
Median CD4+ cells/mm3
(IQR) 328 (225-446) 274 (175-381) 300 (179-415)
Median HIV-1 RNA copies/mL 37521 25118 27692
Median duration of regimen, yrs (IQR) 2.5 (1-3.6) 0.7 (0.2-1.8) 1.7 (0.7-2.5)
*Regimen could consist of single components (EFV + TDF + FTC) or EFV + coformulated TDF/FTC.

Single- vs Multiple-Tablet Regimens in
ART-Naive Pts: Efficacy and Cost
Gatell JM, et al. IAS 2015. Abstract TUPEB264.
Response,*
%
ART Cost,
Euros
Initiation Cost,
Euros
Cost/Responder,*
Euros
Ratio
EFV/TDF/FTC
STR
79
(n = 759)
7370 9414 12,018 1
EFV + TDF +
FTC MTR
64
(n = 483)
6736 8198 12,651 1.04
Other MTR
64
(n = 1531)
8350 11,380 17,733 1.47
*At 48 wks.

C-EDGE Coinfection: Grazoprevir/Elbasvir
for Pts Coinfected With HIV/HCV
 Multicenter, single-arm, open-label phase III trial
Grazoprevir/Elbasvir
HCV NS3/4A inhibitor/HCV NS5A inhibitor
HCV treatment-naive pts
coinfected with HIV and
GT1, 4, or 6 HCV; stable
on ART ≥ 8 wks
(N = 218)
Wk 12
Coformulation dosed orally 100/50 mg QD
Baseline ART Characteristic, % Grazoprevir/Elbasvir (N = 218)
Undetectable HIV-1 RNA on ART 96.8
ART regimen
 Abacavir containing 21.6
 TDF containing 75.2
 Raltegravir 51.8
 Dolutegravir 27.1
 Rilpivirine 17.4
Rockstroh JK, et al. IAS 2015. Abstract TUAB0206LB. Rockstroh JK, et al. Lancet HIV. 2015;2:e319-e327.
 66% GT1a HCV, 60% had HCV RNA > 800,000 IU/mL, 16% cirrhotic

0
100
80
60
20
C-EDGE Coinfection: Key Findings
 No subgroup provided efficacy
advantage or disadvantage, including
ART regimen
 New NS3, NS5A RAVs detected at
failure in 4 of 5 pts who relapsed
 Short-lived HIV-1 RNA increases in 2
pts on ART during GZR/EBV
treatment
– Both resuppressed HIV-1 RNA without
change of ART
 During GZR/EBV Tx, no significant
changes in CD4+ cell count
 GZR/EBV well tolerated: no pt
discontinued for AEs and no serious
treatment-related AEs
SVR12(%)
139/
144
42/
44
27/
28
All Pts GT1a GT1b GT4
96.3 96.5 95.5 96.4
210/
218
SVR12 With 12 Wks GZR/EBV
According to Genotype
Discontinued* 1 0 1 0
Relapse 5 4 0 1
Reinfection 2 1 1 0
*Unrelated to virologic failure.
n/N =
40
Rockstroh JK, et al. IAS 2015. Abstract TUAB0206LB. Rockstroh JK, et al. Lancet HIV. 2015;2:e319-e327. Reproduced
with permission.

ION-4: LDV/SOF for 12 Wks in GT1/4
HIV/HCV-Coinfected Pts
 Phase III, open-label, single-arm study
 98% infected with GT1 HCV, 20% cirrhotic, 34% black
 No efficacy differences among most subgroups, including prior HCV treatment
and presence of cirrhosis
– SVR12 rates significantly lower in black vs nonblack pts (90% vs 99%, P < .001);
differences noted across ART regimens
 HIV disease remained stable during LDV/SOF: CD4+ cell counts remained
stable through treatment, follow-up; no confirmed HIV-1 virologic rebound
noted
 Regimen well tolerated, with no treatment discontinuations due to toxicity
Ledipasvir/Sofosbuvir QD
(n = 335)
Pts with suppressed HIV
infection (HIV-1 RNA < 50
copies/mL) and
GT1/4/6 HCV coinfection
(N = 335)
Wk 12
SVR12, %
96
Naggie S, et al. IAS 2015. Abstract TUAB0202. Naggie S, et al. N Engl J Med. 2015;[Epub ahead of
print].

 Mother’s history
– Treated with zalcitabine from 13 wks gestation to delivery
– At delivery, HIV-1 RNA level 4.63 million copies/mL; CD4+ cell count 81 cells/mm3
 Pt’s history
– ZDV initiated in female pt at birth; HIV-1 RNA undetectable Day 3; HIV-1 DNA
undetectable Days 3 and 14, but detectable at Wk 4
– ZDV interrupted Wk 6; HIV-1 RNA level at Mo 3: 2.17 million copies/mL; ART
initiated (ZDV + ddI + 3TC + RTV)
– LTFU between 5.8 and 6.8 yrs; ART interrupted
– Undetectable HIV-1 RNA level upon return; no further ART since (currently 18 yrs of
age)
 HIV-1 RNA in pt remained < 50 copies/mL from 6.8-18.3 yrs of age except for
1 increase at 12 yrs of age (510 copies/mL)
 Low levels of replicating virus detected after in vitro stimulation of purified
CD4+ T cells
Sustained Remission > 12 Yrs After
Interrupted ART in Perinatally Infected Pt
Sáez-Cirión A, et al. IAS 2015. Abstract MOAA0105LB.

 Randomized, multipart phase IIa trial
AI468002: BMS-955176 + ATV ± RTV for
Treating Pts Infected With HIV
Hwang C, et al. IAS 2015. Abstract TUAB0106LB.
HIV, subtype B–infected
PI- and MI-naive pts
with HIV-1 RNA
≥ 5000 c/mL and
CD4+ cell count
≥ 200 cells/mm3
(N = 28)
BMS-955176 40 mg QD + ATV 300 mg QD
+ RTV 100 mg QD
(n = 8)
(n = 8)
(n = 8)
Day 28*
*Followed through Day 42.
BMS-955176 prevents viral maturation by inhibiting cleavage between p24 and Gag SP1.
ATV 300 mg QD + RTV 100 mg QD
+ TDF 300 mg QD/FTC 200 mg QD
(n = 4)
Max. Median Decline
in HIV-1 RNA through
Day 42 (log10 c/mL)
-2.02
-1.86
-2.23
-2.39
 No serious AEs or discontinuations for AEs
– 1 grade 3/4 Tx-related AE in BMS-955176 80 mg + ATV 400 mg arm (transient neutropenia)

Long-term BMD Changes in HIV-Infected,
ART-Treated Pts
 Case-controlled, observational cohort study
 Assessed HIV-positive pts who had baseline and follow-up DXA
measurements during the A5202/A5224s study and another
DXA measurement during ACTG A5318 trial (n = 97)
– A5224s study: treatment-naive pts randomized to ATV/RTV, EFV
+ TDF/FTC, or ABC/3TC
– Control cases derived from 2 cohorts comprising HIV-uninfected
individuals (n = 614)
 Key baseline characteristics, HIV-infected pts
– Median cumulative TDF use: 5.8 yrs (range: 1.1-7.4)
– Median cumulative PI use: 3.7 yrs (range: 0-7.4)
Grant P, et al. IAS 2015. Abstract TUPDB0103.

Long-term BMD Changes in HIV-Infected,
ART-Treated Pts
 0 to Wk 96: BMD loss at lumbar spine and hip significantly greater in HIV-infected vs
uninfected pts (P < .001)
– Multivariate analysis, HIV-infected pts: BMD loss associated with lower CD4+ cell count (lumbar
spine only), higher HIV-1 RNA, TDF use
 Wk 96 to final: HIV infection associated with significantly greater BMD loss at lumbar spine
(P = .012) but not at hip (P = .99)
– Multivariate analysis, HIV-infected pts: BMD loss associated with total lean body mass
Grant P, et al. IAS 2015. Abstract TUPDB0103. Reproduced with permission.
Change in Lumbar Spine
BMD by Serostatus
HIV-
HIV+
L1L4BMD
Change(%)
0
-2
-4
0 2448 96 144 192 360
Wks
Change in Total Hip BMD by Serostatus
HIV-
HIV+
TotalHipBMD
Change(%)
0
-4
-5
0 2448 96 144 192 360
Wks
-1
-2
-3

 Randomized, controlled, open-label phase IV study
MIDAS: Metabolic Effects of Switching
From EFV/TDF/FTC to DRV/RTV
Hamzah L, et al. IAS 2015. Abstract TUPDB0102.
Switch to DRV/RTV 800/100 mg QD
monotherapy
(n = 32)
HIV-infected
pts with
HIV-1 RNA
< 100 copies/mL
on EFV/TDF/FTC
> 6 mos
(N = 64*)
Continue EFV/TDF/FTC
(n = 32)
Wk 48
 At baseline, the median time on EFV/TDF/FTC was 3.5
yrs (IQR: 2.5-3.9)
*70 pts were randomized; 64 were available for analysis.

MIDAS: Key Results
 4 cases of virologic failure reported in DRV/RTV arm (12.5%)
– Virologic rebound (n = 3), CNS escape (n = 1)
 No significant change in renal parameters
Hamzah L, et al. IAS 2015. Abstract TUPDB0102. Reproduced with permission.
DRV/RTV
EFV/TDF/FTC
P = .03
MeanChange,
TotalHipBMD(%)
Weeks
3
2
1
0
-1
-2
0 48
10.0
5.0
0
-5.0
-10.0
-15.0
MeanUnadjusted
DifferenceatWk48
25(OH)D 1,25(OH)2D
EFV/TDF/FTC
DRV/RTV
-3.5
-16.6
4.8
0.9
Change in Vitamin D
Parameters, Wk 48

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