HIV/AIDS Update From Boston 2014.CCO Official Conference Coverage.March 3-6,2014

March 3-6, 2014
Boston, Massachusetts
HIV/AIDS Update From Boston 2014
CCO Independent Conference Coverage
of the 2014 Annual 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 fromThis program is supported by educational grants from

clinicaloptions.com/hiv
About These Slides
 Users are encouraged to use these slides in their own
noncommercial presentations, but we ask that content
and attribution not be changed. Users are asked to honor
this intent
 These slides may not be published or posted online
without permission from Clinical Care Options
(email permissions@clinicaloptions.com)
Disclaimer
The materials published on the Clinical Care Options Web site reflect the views of the authors of the
CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing
educational grants. The materials may discuss uses and dosages for therapeutic products that have not
been approved by the United States Food and Drug Administration. A qualified healthcare professional
should be consulted before using any therapeutic product discussed. Readers should verify all information
and data before treating patients or using any therapies described in these materials.

Faculty
Joseph J. Eron, Jr., MD
Professor of Medicine and
Epidemiology
University of North Carolina
School of Medicine
Director, AIDS Clinical Trials Unit
University of North Carolina
Chapel Hill, North Carolina
Andrew R. Zolopa, MD
Professor of Medicine
Director, Stanford Positive Care
Program
Principal Investigator, Stanford AIDS
Clinical Trials Unit
Stanford University School of Medicine
Stanford, California
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
Joseph J. Eron, Jr., MD, has disclosed that he has served as a
consultant for AbbVie, Bristol-Myers Squibb, GlaxoSmithKline/ViiV,
Gilead Sciences, Merck, Tibotec/Janssen, and Tobira; has
received funds for research support from GlaxoSmithKline/ViiV;
and has served on a data and safety monitoring board for Vertex.
Joel E. Gallant, MD, MPH, has disclosed that he has received
consulting fees from Gilead Sciences, Janssen, Merck, and
Takara Bio and funds for research support from Bristol-Myers
Squibb, CytoDyn, Gilead Sciences, Sangamo Biosciences, and
ViiV.
Andrew R. Zolopa, MD, has disclosed that he has received
consulting fees from Gilead Sciences and Janssen and funds for
research support from Gilead Sciences, Janssen, and Pfizer and
ViiV.

ACTG 5257: Open-Label ATV/RTV vs RAL
vs DRV/RTV in First-line ART
 Primary endpoints
– Virologic failure: time to HIV-1 RNA > 1000 c/mL (at Wk 16 or before Wk 24) or > 200 c/mL
(at or after Wk 24)
– Tolerability failure: time to discontinuation of randomized component for toxicity
 Composite endpoint: the earlier occurrence of either VF or TF in a given participant
 Switch of regimens allowed for tolerability
Landovitz R, et al. CROI 2014. Abstract 85.
ART-naive patients
with HIV-1 RNA
≥ 1000 c/mL
(N = 1809)
ATV/RTV 300/100 mg QD +
TDF/FTC
(n = 605)
RAL 400 mg BID +
TDF/FTC
(n = 603)
Stratified by HIV-1 RNA
< or ≥ 100,000 c/mL, participation in
metabolic substudy, CV risk
DRV/RTV 800/100 mg QD +
TDF/FTC
(n = 601)
Wk 96 after last
patient enrolled

ACTG 5257: Primary Endpoint Analyses at
Wk 96
 Regimens equivalent
in time to VF
Landovitz R, et al. CROI 2014. Abstract 85. Reproduced with permission.
 Significantly greater
incidence of treatment
failure with ATV/RTV vs
RAL or DRV/RTV
– In part due to high
proportion of pts with
hyperbilirubinemia
 Considering both
efficacy and tolerability,
RAL superior to either
boosted PI
 DRV/RTV superior to
ATV/RTV
Virologic Failure Tolerability Failure Composite Endpoint
Difference in 96-Wk Cumulative Incidence (97.5% CI)
0-10 10 20
ATV/RTV vs RAL
3.4% (-0.7 to 7.4)
DRV/RTV vs RAL
5.6% (1.3 -9.9)
ATV/RTV vs DRV/RTV
-2.2% (-6.7 to 2.3)
0-10 10 20
ATVRTV vs RAL
15% (10-20)
DRV/RTV vs RAL
7.5% (3.2-12.0)
ATV/RTV vs DRV/RTV
7.5% (2.3-13.0)
Favors RAL
Favors DRV/RTV
Favors RAL
0-10 10 20
ATV/RTV vs RAL
13% (9.4-16.0)
DRV/RTV vs RAL
3.6% (1.4-5.8)
ATV/RTV vs DRV/RTV
9.2% (5.5-13.0)
Favors RAL
Favors DRV/RTV

89%
ACTG 5257: Virologic Efficacy
 In ITT analysis with ART
changes allowed (per protocol),
regimens similar in virologic
efficacy at Wk 96 and through
Wk 144
 In ITT analysis when change =
failure (Snapshot), RAL
superior to both boosted PIs at
Wk 96 and DRV/RTV superior
to ATV/RTV at Wks 96 and 144
 Similar mean change in CD4+
count across arms
– ATV/RTV (+284); RAL (+288)
DRV/RTV (+256) cells/mm3
Landovitz R, et al. CROI 2014. Abstract 85.
Reproduced with permission.
1.0
ProportionWithHIV-1RNA≤50c/mL
0.8
0.6
0.4
0.2
0
ITT, Regardless of ART Change
0 24 48 64 80 96 120 144
1.0
0.8
0.6
0.4
0.2
0
ITT, NC = Failure (Snapshot)
RAL
DRV/RTV
ATV/RTV
Study Wk
0 24 48 64 80 96 120 144
88%
94%
63%
73%
80%
RAL
DRV/RTV
ATV/RTV

ACTG 5257: Resistance and Lipids
 VF with drug resistance
occurred more often in pts
initially assigned to RAL[1]
– 3% of those randomized to
RAL had ≥ 1 resistance
mutation and 1.8% had
INSTI mutations
– 1.5% randomized to
ATV/RTV and < 1%
randomized to DRV/RTV
developed resistance
– No major PI mutations
observed
 PI-containing regimens
associated with
significantly greater
increases in TC, LDL-C,
TGs vs RAL at Wk 96[2]
– Lipids remained stable or
decreased in RAL arm
– Lipids changes in
boosted PI arms similar
1. Landovitz R, et al. CROI 2014. Abstract 85. 2. Ofotokun I, et al. CROI 2014. Abstract 746.

P = .004
ACTG 5257: Loss of BMD With First-line
Boosted PI vs RAL
 All arms associated with
significant loss of BMD
through Wk 96 (P < .001)
 Total body BMD loss
significantly greater with
ATV/RTV than either
DRV/RTV or RAL
 At hip and spine, similar
loss of BMD in the PI arms
– Significantly greater loss
in the combined PI arms
than in the RAL arm
ATV/RTV
RAL
DRV/RTV
Combined PI arms
-5
-4
0
-3
-2
-1
-3.9
-1.7
-3.4
-2.9
-3.7
-2.4
-1.8
-4.0
-3.8
-3.6
-1.6
P = .36
Total Hip Total Spine Total Body
P = .005
P = .42
P < .001
P = .001
P = .72
Brown T, et al. CROI 2014. Abstract 779LB. Reproduced with permission.

STRATEGY Trials: Switch to
EVG/COBI/TDF/FTC in Suppressed Pts
 Randomized, open-label switch studies in pts virologically suppressed on an
NNRTI- or boosted PI–based regimen (both with TDF/FTC) for ≥ 6 mos
 Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48
HIV-1 RNA < 50 c/mL,
≤ 2 previous regimens, no
resistance to FTC or TDF
and CrCl ≥ 70 mL/min
STRATEGY-NNRTI[1]
(N = 434)
STRATEGY-PI[2]*
(N = 433)
Switch to EVG/COBI/TDF/FTC QD
(n = 291)
Remain on NNRTI + TDF/FTC
(n = 143)
Switch to EVG/COBI/TDF/FTC QD
(n = 293)
Remain on Boosted PI + TDF/FTC
(n = 140)
1. Pozniak A, et al. CROI 2014. Abstract 553LB. 2. Arribas J, et al. CROI 2014. Abstract 551LB.
*Pts with previous VF ineligible.

STRATEGY-NNRTI: Change to EVG/COBI
Noninferior to Stable NNRTIs at Wk 48
 Regimens: EFV, 78%; NVP, 17%;
RPV, 4%; ETR, < 1%; 74% on
EFV/TDF/FTC; 91% on first
regimen
 Results similar across all baseline
virologic and demographic
subgroups
 3 pts with VF in EVG/COBI arm
and 1 in NNRTI arm
– No pts with resistance in either arm
 5 in the switch arm and 1 in the
NNRTI arm discontinued due to
adverse event
Patients(%)
93
88
Δ +5.3%
(95% CI: -0.5 to +12)
EVG/COBI/TDF/FTC
(n = 290)
Stable NNRTIs
(n = 143)
0
20
40
60
80
100
1
3
< 1
1
6
11
Virologic
Success*
Virologic
Nonresponse
No Data
n =
*HIV-1 RNA < 50 c/mL as defined by FDA Snapshot algorithm

Discontinued for AE, death, or missing data.
Pozniak A, et al. CROI 2014. Abstract 553LB. Reproduced with permission.
271 126 16 16

STRATEGY-PI: Change to EVG/COBI
Better Than Maintaining bPIs at Wk 48
 Regimens: ATV, 40%; DRV, 40%;
LPV, 17%; FPV, 3%; SQV, < 1%;
79% on first regimen
 Results similar across all baseline
virologic and demographic
subgroups
 2 pts with VF in each arm but no
pts with resistance in either arm
 5 in the switch arm and 2 in the
boosted PI arm discontinued due to
adverse event
 Lipids in switch pts
– ↓ TGs vs all bPIs
– ↓ TC, TG, HDL-C vs LPV/RTV
– ↑ HDL-C vs DRV/RTV
Patients,%
94
87
Δ +6.7%
(95% CI: 0.4-13.7)
EVG/COBI/TDF/FTC
(n = 290)
Stable boosted PIs
(n = 139)
0
20
40
60
80
100
< 1
2
1
2
6
12
Virologic
Success*
Virologic
Nonresponse
No Data
n =
*HIV-1 RNA < 50 c/mL as defined by FDA Snapshot algorithm

Discontinued for AE, death, or missing data.
Arribas J, et al. CROI 2014. Abstract 551LB.
272 121 16 16

SINGLE: Dolutegravir + ABC/3TC vs
EFV/TDF/FTC in Naive Pts: 96-Wk Report
 Randomized, noninferiority phase III studies
 Primary endpoint: HIV-1 RNA < 50 c/mL at Wk 48
ART-naive pts
VL ≥ 1000 c/mL
HLA-B*5701 neg
CrCL > 50 mL/min
(N = 822)
DTG 50 mg QD + 2 NRTIs*
(n = 411)
RAL 400 mg BID + 2 NRTIs*
(n = 411)
*Investigator-selected NRTI backbone: either TDF/FTC or ABC/3TC.
ART-naive pts
VL ≥ 1000 c/mL
HLA-B*5701 neg
CrCL > 50 mL/min
(N = 833)
DTG 50 mg QD + ABC/3TC QD
(n = 414)
EFV/TDF/FTC QD
(n = 419)
SPRING-2[1]
(placebo controlled)
SINGLE[2]
(placebo controlled)
DTG 50 mg QD + 2 NRTIs*
(n = 242)
DRV/RTV 800/100 mg QD + 2 NRTIs*
(n = 242)
ART-naive pts
VL ≥ 1000 c/mL
(N = 484)
FLAMINGO[3]
(open label)
1. Raffi F, et al. Lancet. 2013;381:735-743. 2. Walmsley S, et al. N Engl J Med. 2013;369:1807-1818.
3. Feinberg J, et al. ICAAC 2013. Abstract H1464a.

SINGLE: DTG + ABC/3TC Superior to
EFV/TDF/FTC at Both Wk 48 and 96
 Treatment-related study d/c:
3% in DTG vs 11% in EFV arm
– No new treatment-related AEs
in either arm btwn Wks 48-96
 VF at Wk 96: 25 (6%) in each
arm
 0 pts with resistance in DTG
arm; 1 pt with NRTI and 6 pts
with NNRTI resistance in EFV
arm
 CD4+ cell count increase at Wk
96 greater with DTG: +325 vs
+281 cells/mm3
(P = .004)
HIV-1RNA<50copies/mL(%)
88 81
DTG + ABC/3TC
(n = 414)
EFV/TDF/FTC
(n = 419)
0
20
40
60
80
100
80
72
Wk 48[1]
Wk 96[2]
364/
414
338/
419
331/
414
302/
419
Δ 8.0%
(2.3-13.8; P = .006)
Δ 7%
(2-12; P = .003)
1.Walmsley S, et al. N Engl J Med. 2013;369:1807-1818.
2.Walmsley S, et al. CROI 2014. Abstract 543.
n/N =

Snapshot, Wk 96
Overall
Baseline HIV-1 RNA ≤ 100,000 c/mL
Baseline HIV-1 RNA > 100,000 c/mL
Protocol-Defined Virologic Failure
Overall
Treatment-Related Discontinuation = Failure
Overall
SINGLE: HIV-1 RNA < 50 c/mL at Wk 96 by
Baseline HIV-1 RNA
Difference in Proportion (DTG + ABC/3TC - EFV/TDF/FTC)
Favors
EFV/TDF/FTC QD
Favors
DTG + ABC/3TC QD
Walmsley S, et al. CROI 2014. Abstract 543. Reproduced with permission.
-20 -15 -10 -5 0 5 10 2015 25

NEAT-001/ANRS 143: DRV/RTV + RAL vs
DRV/RTV + TDF/FTC in Naive Pts
 Randomized, open-label phase III study
 Primary endpoint
– Virologic: change of treatment before Wk 32 because of insufficient
response or HIV-1 RNA ≥ 50 c/mL at Wk 32 or beyond
– Clinical: death, any new AIDS-defining event, any new non-AIDS event
Raffi F, et al. CROI 2014. Abstract 84LB.
ART-naive pts with
HIV-1 RNA > 1000 c/mL
CD4+ cell count
≤ 500 cells/mm3
(N = 805)
DRV/RTV 800/100 mg QD + RAL 400 mg BID
(n = 401)
Wk 96
DRV/RTV 800/100mg QD + TDF/FTC 300/200 mg QD
(n = 404)
Stratified by country of origin and participation
in virology/immunology substudy

NEAT: RAL + DRV/RTV Noninferior to
TDF/FTC + DRV/RTV at 96 Weeks
 Overall, regimens noninferior by
% reaching composite primary
endpoint of 6 virologic and
clinical endpoints at Wk 96
– RAL: 17.4%; TDF/FTC: 13.7%
– Inferior response in pts with BL CD4
< 200 and a trend toward more
primary endpoints in pts with BL VL
≥ 100K.
 Similar numbers of pts with
PDVF (RAL: n = 66; TDF/FTC: n
= 52)
 No pts with resistance in
TDF/FTC arm vs 5 with
integrase mutations and 1 with
K65R in RAL arm
Raffi F, et al. CROI 2014. Abstract 84LB. Reproduced with permission.
Overall N = 805
BL HIV-1 RNA
< 100,000 c/mL
≥ 100,000 c/mL
n = 530
n = 275
BL CD4+ cell count
< 200/mm3
≥ 200/mm3
n = 123
n = 682
Primary Endpoint at Wk 96:
Adjusted Difference Estimate (95% CI)
RAL - TDF/FTC
-10 0 10 20 30
RAL TDF/FTC
17.4 13.7
7
36
7
27
(P = .09)
39.0
13.6
21.3
12.2
(P = .02)
 Significantly greater mean increases
in fasting lipids in RAL arm

LATTE: GSK1265744 as Part of ART in
Naive Pts: Results of 24-Wk Induction
 GSK1265744 (744), 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
744 10 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)
EFV 600 mg QD + 2 NRTIs QD
(n = 62)
Margolis D, et al. EACS 2013. Abstract PS7/1. Margolis D, et al. CROI 2014. Abstract 91LB.
744 10 mg QD + 2 NRTIs
(n = 60)
744 30 mg QD + 2 NRTIs
(n = 60)
744 60 mg QD + 2 NRTIs
(n = 61)
Wk 48
primary analysis
Stratified by HIV-1 RNA
(≤ vs > 100,000 c/mL) and NRTI Wk 24
Induction Phase* Maintenance Phase

LATTE: Virologic Success During
Induction and Maintenance Phases
 2 pts with PDVF during maintenance; both with INSTI mutations at BL
Margolis D, et al. EACS 2013. Abstract PS7/1. Margolis D, et al. CROI 2014. Abstract 91LB
HIV-1RNA<50c/mLby
SnapshotAlgorithm(%)
100
80
60
40
20
0
BL 2 4 8 12 16 24
Wks
92%
94%
96%
91%
GSK1265744 10 mg (n = 60)
GSK1265744 30 mg (n = 60)
GSK1265744 60 mg (n = 61)
EFV 600 mg (n = 62)
Induction Phase Maintenance Phase
26 28 32 36 40 48

Possible Second Case of Early Triple ART
and “Functional Cure” in HIV+ Child
 Mississippi HIV+ infant treated at 31 hrs of age with ZDV/3TC + NVP until 7
days and then with ZDV/3TC + LPV/RTV to 18 mos, after which ART was
suspended[1]
– At 39 mos of age, remains in remission with undetectable plasma HIV-1 RNA
< 20 copies/mL and normal CD4+ and CD8+ cell counts[2]
 Second case: A different child with high-risk HIV exposure started on triple-
ART at 4 hrs of age[2]
– HIV infection confirmed by positive peripheral blood HIV-1 DNA at 4 hrs and HIV-1
RNA (217 copies/mL) at 36 hrs of age
– Plasma HIV-1 RNA undetectable by 11 days through 8 mos of age and no
replication-competent HIV recovered from resting CD4+ cells at 1 and 3 mos of age
– At 3 mos of age, HIV antibody is indeterminate and CD4+ cell percentages remain
normal for age
– Pt remains on ART
1. Persaud D, et al. CROI 2013. Abstract 48LB. 2. Persaud D, et al. CROI 2014. Abstract 75LB.

HIV-1 Reservoirs Reduced in HIV-Positive
Children With Early ART and Viral Control
 Cross-sectional study of 144
perinatally HIV-infected pts
with long-term (median: 10.2
yrs) virologic suppression on
ART
 Higher proviral burden with
increasing age at virologic
suppression[1]
 In perinatally infected baby
treated early (at 4 hrs of age)
with triple ART, noninduced
proviral genomes detected by
PCR at 1 mo but not at 3 mos
of age[2]
1. Persaud D, et al. CROI 2014. Abstract 72.
2. Persaud D, et al. CROI 2013. Abstract 48LB.
Proviral Reservoir Size by Age of
Virologic Control[1]
Age, yr Median copies HIV DNA/
106
PBMCs
(IQR)
< 1
(n = 14)
4.2 (2.6-8.6)
1-5
(n = 53)
19.4 (5.5-99.8)
> 5
(n =77)
70.7 (23.2-70.7)*
*P < .001 compared with < 1 yr

Lack of Detectable HIV DNA in Subject
With Acute Infection on PrEP
 Pt on PrEP Demo Project, HIV negative at screening but HIV positive at BL
 Received 7 days of oral TDF/FTC PrEP but switched to ART immediately
when test results returned and remains on ART
 Plasma HIV-1 RNA levels: 220 c/mL at PrEP BL; 120 c/mL at 7 days of PrEP;
“detected < 40 c/mL” at ~ 32 days after infection
– All subsequent HIV-1 RNA tests negative
 Single occurrence of low-level cell-associated HIV-1 RNA (4.7 c/million CD4+
T cells) ~ 32 days after infection
– All other HIV-1 RNA and DNA tests have been negative, including those performed
in a colorectal biopsy
 Total CD4+ T cells and CD4+ T-cell subsets also negative for HIV-1 RNA and
DNA
Hatano H, et al. CROI 2014. Abstract 397LB..

PARTNER: Risk of HIV Transmission With
Condomless Sex on Suppressive ART
 Observational study of rate of HIV
transmission in heterosexual and
MSM serodiscordant couples (N =
767 couples)
– HIV+ partner on suppressive ART
– Condoms not used
 Analyses: 6-monthly risk behavior
questionnaire, HIV-1 RNA (HIV+
persons), HIV test (HIV-negative
persons)
 Endpoint: phylogenetically linked
transmissions
 No linked transmissions recorded in
any couple during study period
Rodger A, et al. CROI 2014. Abstract 153LB.
0 20 40 60 80 100
Risk Behaviors, %
Vaginal sex with ejaculation
Vaginal sex
Receptive anal sex
Receptive anal sex with
ejaculation
Only insertive anal sex
MSM
HT♀
HT♂
0 1 2 3 4
Rate of Within-Couple Transmission Events
Per 100 CYFU, % (95% CI)
HT♀
Vaginal sex with ejaculation
(CYFU = 192)
HT♂ Vaginal sex (CYFU = 272)
Receptive anal sex with
ejaculation (CYFU = 93)
Receptive anal sex without
ejaculation (CYFU = 157)
Insertive anal sex (CYFU = 262)
MSM
Estimated rate 95% CI

PROMOTE: EFV vs LPV/RTV in HIV+
Pregnant or Breastfeeding Women
 PROMOTE: open-label
randomized comparison in
HIV+ women between 12-28
wks of gestation in Uganda
– EFV + ZDV/3TC (n = 195)
– LPV/RTV* + ZDV/3TC
(n = 194)
 Analyses of maternal and infant
efficacy and safety, including:
– Maternal VL suppression
(HIV-1 RNA < 400) at delivery
and postpartum Wk 24
– HIV-free infant survival
 HIV transmission in 2 LPV/RTV-treated
infants (in utero, n = 1; breastfeeding, n = 1)
 HIV-free survival: 97.2% in EFV arm vs
92.9% in LPV/RTV arm (P = .1)
 Similar grade 3/4 AEs between arms; more
anemia and neutropenia in LPV/RTV arm
Cohan D, et al. CROI 2014. Abstract 69. Reproduced with permission.
VL Suppression in HIV+ Women
*LPV/RTV dose: 400/100 mg until gestation Wk 30; then
600/150 mg until delivery.
EFV
LPV/RTV
79
HIV-1RNA<400c/mL(%)
100
80
60
40
20
0
Wk 8 on ART Delivery Wk 24 PP
70 72
85 84 85
166/
195
162/
194
166/
195
153/
194
140/
194
137/
195
P < .001
n/N =

VOICE: Injectable Contraception and HIV
Transmission in South African Women
 VOICE (MTN-003): multisite placebo-controlled trial of oral and vaginal
TDF, TDF/FTC as PrEP
– Failed to show efficacy of PrEP, attributed to low rates of adherence[1]
 Comparison of 2 types of contraception and HIV acquisition in South
African women[2]
– DMPA (depot medroxyprogesterone) vs NET-EN (norethisterone
enanthate)
 Overall increased risk of HIV acquisition with use of DMPA vs NET-EN
– Incidence (per 100 PYs): 7.96 vs 5.36 (adjusted HR: 1.43; 95% CI, 1.04-
1.97, P = .026)
 No control group of women not using injectable contraception prevents
estimation of overall risk
1. Marrazzo J, et al. CROI 2013. Abstract 26LB. 2. Noguchi L, et al. CROI 2014. Abstract 847.

GSK1265744 Long-Acting Injections and
Vaginal and Rectal Exposure in Macaques
Vaginal study[1]
GSK1265744 LA 50 mg/kg IM
(n = 6 females) vs placebo (n = 6
females) at Wks 0, 4, 8
Biweekly intravaginal challenge with
CCR5-tropic SHIV162p3 through Wk 12
(up to 22 challenges)
GSK1265744 LA–treated animals
remained aviremic and seronegative
throughout 28 wks
of follow-up
Animals protected throughout multiple
menstrual cycles
Rectal study[2]
Single injection of GSK1265744 LA
50 mg/kg IM (n = 12 males) vs placebo
(n = 4 males) 1 wk before first
challenge
Weekly intrarectal challenge with
CCR5-tropic SHIV162p3 until infection
occurred
1 dose of GSK744 LA delayed
infection by 5 to 10 (median: 8)
challenges (~2 months)
0/59 challenges resulted in infection
when GSK1265744 LA plasma levels >
3 x protein-adjusted IC90
1. Radzio J, et al. CROI 2014. Abstract 40LB. 2. Andrews CD, et al. CROI 2014. Abstract 39.

D:A:D: Abacavir Remains Associated With
Elevated Risk of MI
 Update of analysis of ABC and
risk of acute MI in pts with low,
medium, and high CVD risk
 After initial D:A:D report in March
2008, decline in ABC initiations in
pts with higher CVD risk
Framingham Risk Group
ABC Use as Proportion of
All ART Initiations, %
Before March 2008
 Low/unknown CVD risk 13.6
 Moderate/high CVD risk 17.1
After March 2008
 Low/unknown CVD risk 7.6
 Moderate/high CVD risk 5.3
Sabin C, et al. CROI 2014. Abstract 747LB. Reproduced with permission.
35
30
25
20
15
10
5
0
Low CVD risk
Moderate CVD risk
High CVD risk
CVD risk unknown
Total cohort
2000200120022003200420052006200720082009201020112012
Patients on ABC by CVD Risk
Patients(%)

D:A:D: Current Abacavir Use Associated
With 98% Increase in Acute MI Risk
 Current ABC use remained
associated with increased risk of
acute MI
– Similar RR in post-3/08 group vs
pre-3/08 group, despite decrease in
ABC use in pts with high CVD risk
– Absolute risk in the post 2008
small: 6 cases /2000 PY vs 3
cases/2000 PY or absolute risk ↑
0.15%
 Overall cohort: 941 MI events
during 367,599 PYs
– 0.47/100 PYs (95% CI: 0.42-0.52)
with current ABC
– 0.21 (95% CI: 0.19-0.22) with no
current ABC
No Current ABC
Events/PYs 600/295,642 425/169,417 175/126,225
Rate/100 PYs
0.20
(0.19-0.22)
0.25
(0.23-0.28)
0.14
(0.12-0.16)
Current ABC
Events/PYs 341/71917 247/40833 94/31084
Rate/100 PYs
0.47
(0.42-0.52)
0.61
(0.53-0.68)
0.30
(0.24-0.36)
Sabin C, et al. CROI 2014. Abstract 747LB.
5
4
3
2
1
0.7
Overall Pre-3/08 Post-3/08
Adjusted Relative Rate of MI
in Pts Currently Receiving ABC
1.98
(1.72-2.29)
1.97
(1.68-2.33)
1.97
(1.43-2.72)

Incidence of MI in HIV+ vs HIV- Subjects in
Kaiser Cohort
 Retrospective analysis of
Kaiser cohort EMRs during
1996-2011 for inpatient MI
diagnosis
 HIV-/HIV+ pts matched 10:1
 MI rates in HIV+ and HIV-
converged over time
– 40% increased risk of MI in
HIV+ pts overall, but
difference no longer
observed in most recent yrs
Klein D, et al. CROI 2014. Abstract 737. Reproduced with permission.
Framingham Risk Score
Components, 2010-11 HIV+ HIV- P
Value
Mean Framingham score,
10-yr risk of MI, % 9.2 9.6 < .001
Male, % 90.7 90.4 .42
Mean age, yrs 47.9 48.5 < .001
TC > 200 mg/dL, % 30.0 39.6 < .001
HDL-C < 40 mg/dL, % 39.4 26.2 < .001
Hx of hypertension, % 28.5 26.2 < .001
Hx of smoking, % 48.7 34.9 < .001
400
300
200
100
0
1996-99 2000-03 2004-07 2008-09 2010-11
MIsper100,000PY
HIV+
HIV-

ACTG 5280: High-Dose Vitamin D and
Calcium Attenuate Bone Loss in EFV Pts
 Randomized, double-blind trial in
pts initiating TDF/FTC/EFV with
baseline vitamin D 10-75 ng/mL
– Vitamin D3 4000 IU/day plus
– Calcium carbonate 1000 IU/day
 Significant, 50% reduction in loss
of hip BMD at Wk 48 in treated pts
 Smaller nonsignificant difference in
spine BMD in treated pts
 Smaller increase in markers of
bone turnover in treated pts
Overton ET, et al. CROI 2014. Abstract 133. Reproduced with permission.
5
0
-5
-10
-15
Total Hip Lumbar Spine
-1.46
-3.19
-1.41
-2.91
P < .001 P = .085
Placebo
Decline in BMD From Baseline to Wk 48
Lower and upper edges of box indicate 25th and 75th
percentiles; lines inside box indicate median.
ChangeinBMD(%)
Vitamin D/calcium

Risk of New Onset Depression in
CHARTER Cohort
 Longitudinal follow-up of 223
participants in CHARTER cohort
taking ART from 2004-2009
– No depression at BL
– ≥ 3 LPs per subject
– 2496 person-mos follow-up
 Higher incidence of new-onset
depression with detectable HIV-1
RNA in CSF
 Detectable VL in CSF, but not
plasma, at any previous visit
associated with 4.7-fold increased
risk of new-onset depression
Hammond E, et al. CROI 2014. Abstract 33.
Incidence of Depression in CHARTER
Cohort
Incidence/100
Person-Mos
All subjects 9.2
CSF HIV-1 RNA ≤ 50 c/mL 8.2
CSF HIV-1 RNA > 50 c/mL 19.6

Cumulative Viral Load Predicts Mortality in
ART-Treated Patients
 Estimated cumulative VL
(viremia copy-yrs) assessed
in 33,563 pts at 17 sites of
ART Cohort Collaboration
 After adjusting for age, sex,
risk group, BL and time-
related VL, and cohort,
viremia copy-yrs stratum
predicted
– All-cause mortality
– AIDS-related mortality
Mugavero M, et al. CROI 2014. Abstract 565. Reproduced with permission.
2.50
2.25
2.00
1.75
1.50
1.25
1.00
0.75
0.5
00-3.0
3.0-3.5
3.5-4.0
4.0-4.5
4.5-4.75
4.75-5.0
5.0-5.25
5.25-5.5
5.5-5.75
>5.75
HR
Log10 Viremia Copy-Yrs
Hazard of All-Cause Mortality
by Viremia Copy-Yrs Deciles
(Controlling for Cross-sectional VL)

Normalization of CD4/CD8 Ratio and
Non-AIDS Events in ICONA Cohort
 Analysis of 3236 pts with virologic
suppression on ART and CD4/CD8
ratio ≤ 0.8
– 458 pts reached CD4/CD8 ≥ 1
– Median time to normalization: 10.1 yrs
– Younger pts, those starting ART in
recent yrs, and those with higher
CD4+ counts more likely to normalize
 Current CD4/CD8 ratio predicted
incidence of clinical progression
(serious non-AIDS37–related events
or all-cause death)
– Remained predictive after adjusting for
current CD4+ cell count
Mussini C, et al. CROI 2014. Abstract 753. Reproduced with permission.
Time
Probability of CD4/CD8
Normalization (95% CI)
1 yr 4.4 (3.7-5.2)
2 yrs 11.5 (10.2-13.0)
5 yrs 29.4 (26.7-32.4)
Current CD4/CD8
Ratio
Incidence of Clinical
Progression (95% CI)
< 0.30 4.8 (3.9-5.9)
0.30-0.45 2.4 (1.9-3.1)
> 0.45 2.0 (1.7-2.3)

Prevalence of Drug Resistance Mutations
in Treatment-Naive Patients, 2000-2013
 Baseline plasma samples from
4 phase III trials (GS 903, 934,
104, 111)
– 1617 samples analyzed for
integrase mutations
– 2531 analyzed for protease or
RT mutations
 Substantial ↑ in prevalence of
NNRTI resistance, modest ↑ in
PI resistance
 Stable prevalence of NRTI
resistance (mostly TAMs)
– M184V/I ≤ 0.2%; K65R ≤ 0.2%
 Little evidence of transmitted INSTI
resistance over period
– Mostly T97A polymorphism
2000 (GS-903)
2003 (GS-934)
2013 (GS-104/GS-
111)
0
2
NNRTI
10
4
6
8
NRTI PI INSTI
0.5 1.0
0
4.2
8.7
3.2
2.6 2.6
1.2
2.4
2.9
1.4
Margot NA, et al. CROI 2014. Abstract 578.

Bulk vs Sensitive Genotyping for
Detection of Transmitted Drug Resistance
 Re-examination of 1070 de-identified samples in CDC Variant Atypical Resistance HIV
Surveillance database of ART-naive pts in 2009-2011
 Use of sensitive testing increased total prevalence of transmitted resistance from 7.9%
to 13.6% (P < .0001)
 Analysis of 5 mutations as sentinel markers of transmitted resistance
0.8 1.1
Specimens(%)
3.0
2.4
1.8
1.2
0.6
0
K65R Y181C M184V
0.3
1.4
0
1.7
2.7
1.4
M41L
10
8
6
4
2
K103N
7.0
8.4
P < .0001
P < .0001
P < .0001
Li J, et al. CROI 2014. Abstract 87.
Bulk
Sensitive
0
Transmitted Resistance Mutations
18 9 29 3 15 12 15 75 90n =

PHOTON-1: Sofosbuvir + Ribavirin in GT1-
3 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)
– 95% on ART: TDF/FTC, 100%: EFV: 35%; ATV/RTV: 17%; DRV/RTV: 15%; RAL: 16% RPV: 6%
 10% of pts with cirrhosis
 Primary endpoint: SVR12
Naggie S, et al. CROI 2014. Abstract 26.
Wk 24
Sofosbuvir + Ribavirin
(n = 114)
(n = 41)
(n = 68)
Wk 12
Tx-naive GT1
Tx-naive GT2/3
Tx-expd GT2/3
SVR12, % (n/N)
76 (87/114)
GT2: 88 (23/26)
GT3: 67 (28/42)
GT2: 92 (22/24)
GT3: 94 (16/17)
Sofosbuvir 400 mg QD; weight-based ribavirin 1000 or 1200 mg/day

SYNERGY: Sofosbuvir/Ledipasvir FDC ±
GS-9669 or GS-9451 in GT1 HCV Patients
 NIAID nonrandomized, parallel-arm phase II trial
– HCV-monoinfected patients
– Sofosbuvir (nucleotide polymerase inhibitor) coformulated with ledipasvir (NS5A
inhibitor) + either GS-9669 (nonnucleoside polymerase inhibitor) or GS-9451 (PI)
Tx naive GT1, F0-F4
SOF/LDV FDC + GS-9669
(n = 20)
SOF/LDV FDC
(n = 20)
Tx naive GT1, F0-F3
SOF/LDV FDC + GS-9451
(n = 20)
Wk 12
Sofosbuvir/ledipasvir 400/90 mg QD; GS-9669 500 mg QD; GS-9451 80 mg QD.
Wk 6
Tx naive GT1, F0-F3
Kohli A, et al. CROI 2014. Abstract 27LB.
SVR12, % (n/N)
100 (20/20)
95 (19/20)
100 (20/20)

PEARL-III: ABT-450/RTV/ABT-267 + ABT-
333 +/- RBV in Noncirrhotic GT1b HCV Pts
 Randomized, placebo-controlled phase III study
– HCV-monoinfected patients
– ABT-450 (RTV-boosted PI) coformulated with ABT-267 (NS5A inhibitor) + ABT-333
(nonnucleoside polymerase inhibitor) + RBV
Ferenci P, et al. CROI 2014. Abstract 29LB.
HCV Tx-naive
noncirrhotic pts
with GT1b HCV
(N = 419)
ABT-450/RTV/ABT-267 + ABT-333 + RBV
(n = 210)
Wk 12
ABT-450/RTV/ABT-267 + ABT-333
(n = 209)
ABT-450/RTV/ABT-267 150/100/25 mg QD; ABT-333 250 mg BID; weight-based RBV 1000 or 1200
mg/day
SVR12, % (n/)
99.5 (209/210)
99.0 (207/209)

Go Online for More CCO Coverage
of the 2014 Retrovirus Meeting!
Capsule Summaries of key data
Coming soon! Expert Analysis of key studies with expert faculty
commentary
clinicaloptions.com/boston2014

HIV/AIDS Update From Boston 2014.CCO Official Conference Coverage.March 3-6,2014

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Viewers also liked

Viewers also liked (18)

Similar to HIV/AIDS Update From Boston 2014.CCO Official Conference Coverage.March 3-6,2014

Similar to HIV/AIDS Update From Boston 2014.CCO Official Conference Coverage.March 3-6,2014 (20)

More from hivlifeinfo

More from hivlifeinfo (19)

Recently uploaded

Recently uploaded (20)

HIV/AIDS Update From Boston 2014.CCO Official Conference Coverage.March 3-6,2014

Editor's Notes