Clinical Impact of New Data From CROI 2017 Expert faculty members Joel E. Gallant, MD, MPH, and Charles B. Hicks, MD, summarize key studies from this important annual conference. Format: Microsoft PowerPoint (.ppt) File size: 1.25 MB Date posted: 3/3/2017

1. Clinical Impact of New Data From CROI 2017
CCO Independent Conference Coverage*
of the 2017 Conference on Retroviruses and Opportunistic Infections,
February 13-16, 2017
*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 educational grants from Gilead Sciences, Merck, Theratechnologies Inc,
and ViiV Healthcare

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3. Faculty
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
Charles B. Hicks, MD
Professor of Clinical Medicine
Director, Owen Clinic
University of California, San Diego
San Diego, California

4. Faculty Disclosures
Joel E. Gallant, MD, MPH, has disclosed that he has received
consulting fees from Bristol-Myers Squibb, Gilead Sciences, Merck,
Theratechnologies Inc, and ViiV and funds for research support
from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen,
Merck, Sangamo, and ViiV.
Charles B. Hicks, MD, has disclosed that he has received
consulting fees from Janssen, Merck, and ViiV and royalties from
UpToDate, Inc.

5. Prevention

6. STIs and STI PEP in PrEP Users
 IPERGAY: randomized double-blind trial of event-driven oral FTC/TDF vs PBO as
on-demand PrEP in high-risk MSM in France and Canada[1]
– 86% reduction in HIV infection risk with on-demand PrEP (P = .002); 41% acquired STIs
 Among 220 MSM initiating PrEP at STD clinic in Seattle, WA, from Sept 2014 to
June 2016[2]
:
– Decreased rate of condom use during receptive anal intercourse with HIV+ partners and
increased rates of CT and GC diagnosis following PrEP initiation (vs pre-PrEP baseline)
 Current study enrolled participants from open-label IPERGAY extension[3,4]
– 232 men randomized 1:1 to on-demand doxycycline (two 100-mg pills within
72 hrs following condomless intercourse; no more than 6 pills/wk) vs no PEP
– All participants given condoms, risk-reduction counseling, HIV & STI testing every 8 wks
1. Molina JM, et al. N Engl J Med. 2015;373:2237-2246. 2. Montano MA, et al. CROI 2017. Abstract
979. 3. Molina JM, et al. IAC 2016. Abstract WEAC0102. 4. Molina JM, et al. CROI 2017. Abstract
91LB. Slide credit: clinicaloptions.com

7. On-Demand Doxycycline STI PEP for MSM Using
On-Demand Oral FTC/TDF PrEP
 Median follow-up: 8.7 mos
 73 new STIs: 28 in PEP arm, 45
in no PEP arm
 Rate of GI AEs: 53% in PEP
arm vs 41% in no PEP arm (P
= .07)
– 8 pts (7%) discont. PEP for AEs
 Although effective for reducing
chlamydia and syphilis rates in the
short term, concerns about
antibiotic resistance and long-term
safety/efficacy need to be
addressed before widespread
adoption is considered
STI HR (95% CI) P Value
Any STI 0.53 (0.33-0.85) .008
Gonorrhea 0.83 (0.47-1.47) .52
Chlamydia 0.30 (0.13-0.70) .006
Syphilis 0.27 (0.07-0.98) < .05
Molina JM, et al. CROI 2017. Abstract 91LB. Slide credit: clinicaloptions.com

8. Case Report: Wild-Type HIV-1 Infection in MSM
Adherent to PrEP
 50-yr-old MSM using daily oral
FTC/TDF PrEP in Amsterdam Pre-
Exposure Prophylaxis project
– Reported drug use during sex,
excellent PrEP adherence
– Median number of condomless
anal sex partners per day in each
mo following PrEP initiation
ranged from 2-5
– Tested positive for rectal STIs -
gonorrhea (2x) and chlamydia
 HIV Ag/Ab results negative at
PrEP start and after 1, 3, 6 mos
– After 8 mos: fever, dysuria, HIV Ab
positive, Ag negative, and HIV-1
RNA negative; PrEP discontinued
and HIV-1 RNA detectable 3 wks
later; no drug resistance detected
– Dried blood spot TFV-DP levels
protective at Mos 6 and 8
 HIV-1 RNA suppressed 1 mo after
initiating ART
Hoornenborg E, et al. CROI 2017. Abstract 953. Slide credit: clinicaloptions.com

9. Wild-Type HIV Infection While Adherent to PrEP
 First reported case of WT HIV infection in person with protective TFV-
DP levels
– Seroconversion pattern atypical: no HIV DNA in bulk PBMCs, no HIV
DNA or RNA in 3 sigmoid biopsies at time of seroconversion
– Hypothetical mechanisms of infection
– High number of repeated HIV exposures with or without mucosal damage?
– Decreased TDF and/or FTC levels in rectal mucosa?
 Highlights importance of periodic HIV testing during PrEP use and
awareness of potential for atypical seroconversion patterns
Hoornenborg E, et al. CROI 2017. Abstract 953. Slide credit: clinicaloptions.com

10. New Data on Currently Available ART

11. Studies 104/111: TAF vs TDF in Treatment-Naive
Pts
 Parallel, randomized, double-blind, active-controlled phase III studies
– Primary endpoint: HIV-1 RNA < 50 c/mL at Wk 48 (FDA Snapshot)
Arribas JR, et al. CROI 2017. Abstract 453. Sax PE, et al. Lancet. 2015;385:2606-2615. Slide credit: clinicaloptions.com
EVG/COBI/FTC/TAF*
single-tablet regimen
(n = 866)
EVG/COBI/FTC/TDF†
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 48:
Primary Endpoint Wk 144
*150/150/200/10 mg once daily.
†
150/150/200/300 mg once daily.

12. Initial ART With E/C/F/TAF Superior to E/C/F/TDF
at Wk 144
 Efficacy similar across pt
subgroups, trending toward or
significantly better with TAF in
each group
– By baseline HIV-1 RNA, baseline
CD4+ cell count, adherence, age,
sex, race, region
 Virologic failure with resistance by
Wk 144: 1.4% in each arm
Arribas JR, et al. CROI 2017. Abstract 453. Sax PE, et al. Lancet. 2015;385:2606-2615. Slide credit: clinicaloptions.com
0
20
60
40
80
100
48 96 144 48 96 144 48 96 144Wk:
Virologic
Success
Virologic
Failure
No Data
E/C/F/TAF (n = 866)
E/C/F/TDF (n = 867)
92 90
87 85 84
80
4 4 5 4 5 4 4 6
9 11 11
16
Pts(%)
Treatment Difference
Wk 48: 2.0% (95% CI: -0.7% to 4.7%)
Wk 144: 4.2% (95% CI: 0.6% to 7.8%;
P = .02)

13. Initial ART With E/C/F/TAF vs E/C/F/TDF: Wk 144
Safety Outcomes
 Rate of discontinuation for AEs
higher with TDF vs TAF regimen
– 3.3% vs 1.3% (P = .01)
 Spine and hip BMD loss greater
with TDF vs TAF regimen
– 6 discontinuations for bone AEs in
TDF arm vs 0 in TAF arm
 TC, LDL, and HDL increases
greater with TAF vs TDF regimen,
but no difference in TC:HDL ratio
– Rates of lipid-modifying therapy
initiation similar: 5.5% vs 5.8%
Slide credit: clinicaloptions.com
Renal Events Leading to
Discontinuation, n
E/C/F/TAF
(n = 866)
E/C/F/TDF
(n = 867)
Proximal renal tubulopathy 0 4
Cr elevation or eGFR
decrease
0 3
Renal failure 0 2
Nephropathy 0 1
Proteinuria 0 1
Bladder spasm 0 1
Total 0 12
Arribas JR, et al. CROI 2017. Abstract 453.

14. Switch to EVG/COBI/FTC/TAF in Virologically
Suppressed Women
 WAVES: international, randomized, double-blind phase III trial comparing
EVG/COBI/FTC/TDF vs ATV/RTV + FTC/TDF in 575 treatment-naive women[1]
 Women completing 48 wks ATV/RTV + FTC/TDF in WAVES rerandomized in current trial[2]
Slide credit: clinicaloptions.com1. Squires K, et al. Lancet HIV. 2016;3:e410-e420. 2. Hodder S, et al. CROI 2017. Abstract 443.
Switch to EVG/COBI/FTC/TAF
(n = 159)
Continue ATV/RTV + FTC/TDF
(n = 53)
Virologically suppressed
women who completed 48
wks of ATV/RTV +
FTC/TDF in WAVES trial
(N = 212)
Wk 48 Wk 48 HIV-1 RNA < 50 c/mL
by FDA Snapshot
Difference:
7.5% (95% CI:
-1.2 to 19.4)
94%
87%
 No treatment-emergent resistance in either treatment arm
 At Wk 48, pts receiving TAF had higher mean % increase in lumbar spine and total hip BMD,
improved renal safety markers, and greater lipid increases vs TDF regimen, but no
difference in TC:HDL ratio

15. Current Status of INSTI Resistance in the United
States
 Transmitted INSTI resistance remains rare and rates of on-treatment INSTI
resistance continue to be low[1-3]
 CDC National HIV Surveillance System[1]
:
– Prevalence of INSTI resistance for HIV diagnoses through 2014: 65/14,468 (0.4%)
– Pre-ART prevalence of INSTI resistance (ie, transmitted): 2/4631 (0.04%)
 UNC CFAR HIV Clinical Cohort[2]
:
– 2015 INSTI resistance prevalence in 685 pts who began ART in 2007 or later: 1%
 In modeling study assuming 0.1% rate of transmitted INSTI resistance and
$250 cost per test: pre-ART INSTI resistance testing correlated with worse
outcomes, higher costs vs no test[3]
1. Hernandez AL, et al. CROI 2017. Abstract 478. 2. Davy T, et al. CROI 2017. Abstract 483.
3. Koullias Y, et al. CROI 2017. Abstract 493. Slide credit: clinicaloptions.com

16. Case Report: Emergence of INSTI Resistance in
Acute Infection Treated With DTG + FTC/TDF
 45-yr-old man, no PMH, presented with P.
jirovecii and new acute HIV diagnosis
 Initiated DTG + FTC/TDF and discharged;
readmitted to ICU several days later for
worsened hypoxia
 HIV-1 RNA increased after readmission
despite med adherence (including directly
observed therapy in hospital) and no
concurrent divalent cation use
– DRV/RTV added, HIV-1 RNA decreased
– Pneumonia improved and pt discharged
 HIV-1 RNA remains suppressed;
DRV/RTV switched to RPV for diffuse
erythroderma
 Rapid INSTI emergence by deep seq: eg,
Q148K population increased from 0.0015%
at Timepoint 1 to 20.9% at Timepoint 3
Fulcher JA, et al. CROI 2017. Abstract 500LB. Reproduced with permission. Slide credit: clinicaloptions.com
Days
0
200
400
600
800
1000
101
102
103
104
105
106
107
0 20 40 60 80 100
HIV-1RNA(c/mL)
CD4+Count(cells/mm3
)
Initiated DTG/FTC/TDF; GT (clinical assay):
RT: V118I, F214L; IN: Not Tested
Added DRV/RTV; GT (clinical assay):
RT: M184V, V118I, F214L; IN: G163E
Time Points of IN
Deep sequencing
1
2
3

17. Switch/Simplification

18. SWORD 1 & 2: Switch From Suppressive ART to
DTG + RPV Dual Therapy
 Randomized, open-label, multicenter phase III trials
– Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48 (ITT-E
snapshot)
 70% to 73% of pts receiving TDF at baseline
Llibre JM, et al. CROI 2017. Abstract 44LB. Slide credit: clinicaloptions.com
Switch to DTG + RPV
(n = 513)
Continue Baseline ART
(n = 511)
HIV-infected pts with
HIV-1 RNA < 50 c/mL for
≥ 12 mos while receiving
first-line or second-line ART
with 2 NRTIs + INSTI,
NNRTI, or PI; no previous
VF; HBV negative
(N = 1024)
Wk 52 Wk 148
Switch to DTG + RPV
Continue DTG + RPV
DTG + RPV

19. Switch From Suppressive ART to DTG + RPV
Noninferior to Continued Baseline ART at Wk 48
 1 pt with confirmed criteria for
virologic withdrawal at Wk 36 in
DTG + RPV arm had K101K/E
– Documented nonadherence at VF
– Resuppressed with continued
DTG + RPV
– No INSTI resistance
Llibre JM, et al. CROI 2017. Abstract 44LB. Reproduced with permission. Slide credit: clinicaloptions.com
Virologic
Nonresponse
Wk 48
HIV-1 RNA
< 50 c/mL
No Data
100
80
60
40
20
0
Pts(%)
95 95
< 1 1
5 4
Treatment difference:
-0.2%
(95% CI: -3.0% to 2.5%)
DTG + RPV (n = 513)
Baseline ART (n = 511)

20. Switch From Suppressive ART to DTG + RPV:
Safety Outcomes
 AE rates generally similar between
treatment arms through Wk 52
– Numerically higher rate of drug-
related grade 1/2 AEs with switch:
17% vs 2%
– Numerically higher rate of
withdrawal for AEs with switch: 4%
vs < 1%
 No notable change in serum lipid
values from baseline to Wk 48 in
either treatment arm
Llibre JM, et al. CROI 2017. Abstract 44LB. Reproduced with permission. Slide credit: clinicaloptions.com
Bone-specific
alkaline
phosphatase
Osteocalcin Procollagen 1
N-terminal
propeptide
Bone Turnover Marker
DTG + RPV Baseline ART
0
20
60
40
80
Mean(µg/L)
Baseline
Wk 48
15.9
12.9
100 Baseline
Wk 48
16.2 17.1
23.8
19.0
24.0 23.1
53.0
45.6
55.354.7
P < .001
P < .001
P < .001

21. ANRS 167 LAMIDOL: Switch to DTG + 3TC in
Virologically Suppressed Pts on Triple ART
 Noncomparative, open-label, single-arm multicenter trial
– Primary endpoint: therapeutic success at Wk 56 (ie, after 48 wks of dual
therapy)
– Therapeutic failure: HIV-1 RNA > 50 copies/mL, interruption, lost to f/u, death
Joly V, et al. CROI 2017. Abstract 458. Slide credit: clinicaloptions.com
DTG 50 mg QD +
2 NRTI†
HIV-infected pts with
HIV-1 RNA ≤ 50 copies/mL
for ≥ 2 yrs on first-line ART;
≤ 2 ART modifications
allowed, except within 6 mos
of study start; CD4+ cell count
> 200 cells/mm3
(N = 110)
Wk 8* Wk 56
*Pts with HIV-1 RNA ≤ 50 copies/mL proceeded to phase II.
†
In phase I, third agent in regimen replaced with DTG; baseline NRTI
backbone maintained.
DTG 50 mg QD +
3TC 300 mg QD
(n = 104)
Phase I Phase II

22. LAMIDOL Interim Analysis: Switch to DTG + 3TC
Effective in Maintaining Viral Suppression
 97% (101/104) pts maintained
therapeutic success through 40
wks of dual therapy (study Wk 48)[1]
– No INSTI resistance in 3 pts with
virologic failure
– 7 pts with serious AEs, only 2
related to dual therapy
 DTG + 3TC dual therapy currently
under phase III evaluation as both
initial ART[2,3]
and as a switch
strategy for virologically
suppressed pts[4]
1. Joly V, et al. CROI 2017. Abstract 458. 2. ClinicalTrials.gov. NCT02831673. 3. ClinicalTrials.gov.
NCT02831764 4. ClinicalTrials.gov. NCT02263326. Slide credit: clinicaloptions.com
Therapeutic Success, n/N* (%) DTG + 3TC
Wk 0 (entry; on BL triple therapy) 110/110 (100)
Wk 8 (end of phase I, start of phase II) 104/104 (100)
Wk 12 104/104 (100)
Wk 16 103/104 (99)
Wk 24 103/104 (99)
Wk 32 103/104 (99)
Wk 40 102/104 (98)
Wk 48 101/104 (97)
*Pts enrolled in phase I, N = 110; pts enrolled in phase II, N = 104.

23. DOMOMO: Switch to DTG Monotherapy in
Virologically Suppressed Pts Not Sufficient
 Randomized comparison of switch to DTG 50 mg QD monotherapy vs
continued baseline ART for 24 wks in virologically suppressed pts with no
previous VF[2]
 At Wk 24, DTG monotherapy noninferior to continued baseline ART for
maintained HIV-1 RNA < 200 c/mL
– After 24 wks, all pts allowed to switch to DTG QD monotherapy
 Study d/c early because of high VF rate after 48 wks of DTG monotherapy
– VF in 8/77 pts with DTG monotherapy vs 3/152 pts on combination ART in
concurrent control group (P = .03)
– Among 6 VF cases with resistance data in DTG monotherapy group,
3 developed INSTI resistance
Wijting I, et al. CROI 2017. Abstract 451LB. Slide credit: clinicaloptions.com

24. Emergent INSTI Resistance After Switch to DTG
Monotherapy
 International, multicenter retrospective study evaluated
virologically suppressed pts switched from combination ART to
DTG 50 mg QD monotherapy
– Pts with history of VF on INSTI and INSTI resistance excluded
 11 of 122 pts switched to DTG monotherapy experienced VF
– 9 of 11 had genotypic INSTI resistance at VF
– INSTI resistance pathways varied: 92Q/155H (n = 1); 97A/155H (n
= 1); 155H/148R (n = 1); 118R (n = 2); 148K (n = 1); 148H (n = 2);
148R (n = 1)
Blanco JL, et al. CROI 2017. Abstract 42. Slide credit: clinicaloptions.com

25. Investigational Antiretroviral Drugs

26. Doravirine or Darunavir + RTV Both With
FTC/TDF or ABC/3TC in Treatment-Naive Pts
 Doravirine: next-gen NNRTI, unique resistance profile, low DDI potential
 Multicenter, randomized, double-blind phase III trial
– Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48
14-day
follow-up
Slide credit: clinicaloptions.comMolina JM, et al. CROI 2017. Abstract 45LB.
Wk 96
DOR 100 mg QD +
FTC/TDF or ABC/3TC QD +
Placebo for DRV + RTV
(n = 385)
DRV 800 mg + RTV 100 mg QD +
FTC/TDF or ABC/3TC QD +
Placebo for DOR
(n = 384)
HIV-infected pts
with HIV-1 RNA
≥ 1000 copies/mL
within 45 days of Day 1;
no previous ART;
no resistance to study drugs
(N = 769)
Stratified by HIV-1 RNA > 100,000 c/mL,
baseline NRTI
Wk 48

27. Doravirine Is Noninferior to DRV + RTV at Wk 48
(FDA Snapshot)
 Efficacy similar in both arms
regardless of baseline HIV-1 RNA or
CD4+ cell count
 No drug resistance detected in pts
with PDVF through Wk 48 in either
arm
– n = 1 pt with noncompliance
discontinued at Wk 24, developed
DOR and FTC resistance
Slide credit: clinicaloptions.comMolina JM, et al. CROI 2017. Abstract 45LB. Reproduced with permission.
Virologic
Nonresponse
Wk 48
HIV-1 RNA
< 50 c/mL
No Data
100
80
60
40
20
0
Pts(%)
84 80
11 13
5 7
Treatment difference: 3.9%
(95% CI: -1.6% to 9.4%)
DOR + 2 NRTIs (n = 383)
DRV + RTV + 2 NRTIs (n = 383)

28. Doravirine vs DRV + RTV in Combination With
FTC/TDF or ABC/3TC: Safety
Slide credit: clinicaloptions.comMolina JM, et al. CROI 2017. Abstract 45LB. Reproduced with permission.
AE, %
DOR
(n = 383)
DRV + RTV
(n = 383)
≥ 1 AE 80 78
Treatment-related AE 31 32
Serious AE 5 6
Discontinuation for AE 2 3
AEs of clinical interest
Rash*
Neuropsychiatric†
7
11
8
13
Fasting Lipid Δ From
BL to Wk 48, mg/dL
DOR
(n = 383)
DRV + RTV
(n = 383)
LDL-c* -4.51 9.92
Non-HDL-c* -5.3 13.75
Cholesterol -1.37 17.9
Triglyceride -3.14 21.97
HDL-c 3.94 4.15
*Discontinued due to rash: n = 2 in DOR arm; n = 1 in
DRV + RTV arm.
†
No discontinuation for neuropsychiatric conditions.
*P < .0001 for DOR vs DRV + RTV.

29. Bictegravir + FTC/TAF vs DTG + FTC/TAF in
Treatment-Naive Pts
 Bictegravir: novel QD INSTI, active against most INSTI RAVs, low DDI
potential, half-life ~ 18 hrs, no food requirement with dosing, primarily
metabolized by CYP3A4 and UGT1A1
 Randomized, double-blind, active-controlled phase II trial
– Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 24
Open-
label
extension
Slide credit: clinicaloptions.com
Sax PE, et al. CROI 2017. Abstract 41. Sax PE, et al. Lancet HIV. 2017;[Epub ahead of print].
Zhang H, et al. CROI 2017. Abstract 40.
Wk 48
BIC + FTC/TAF QD +
Placebo for DTG QD
(n = 65)
DTG + FTC/TAF QD +
Placebo for BIC QD
(n = 33)
Wk 24
HIV-infected pts
with HIV-1 RNA
≥ 1000 copies/mL;
CD4+ ≥ 200 cells/mm3
;
no previous ART;
HBV and HCV negative
(N = 98)

30. Bictegravir + FTC/TAF vs DTG + FTC/TAF: Wk 24
and Wk 48 Efficacy (FDA Snapshot)
 No drug resistance detected in either arm through Wk 48
Slide credit: clinicaloptions.comSax PE, et al. CROI 2017. Abstract 41. Reproduced with permission.
Virologic
Failure
Wk 48
Virologic
Success
No Data
100
80
60
40
20
0
97
91
2 6 2 3
Treatment difference: 6.4%
(95% CI: -6% to 18.8%)
Virologic
Failure
Wk 24
Virologic
Success
No Data
100
80
60
40
20
0
Pts(%)
97
94
3 6
0 0
Treatment difference: 2.9%
(95% CI: -8.5% to 14.2%)
BIC + FTC/TAF (n = 65) DTG + FTC/TAF (n = 33)

31.  Difficult to conclude on safety from small
study, but 4 fully enrolled phase III trials
now evaluating efficacy, safety, tolerability
of coformulated BIC/FTC/TAF
Bictegravir + FTC/TAF vs DTG + FTC/TAF: AEs
and Lab Abnormalities
Slide credit: clinicaloptions.comSax PE, et al. CROI 2017. Abstract 41. Reproduced with permission.
Any Grade AE Occurring
in ≥ 5% in Either Arm, %
BIC + FTC/TAF
(n = 65)
DTG + FTC/TAF
(n = 33)
Diarrhea 12 12
Nausea 8 12
Headache 8 3
URTI 8 0
Fatigue 6 6
Arthralgia 6 6
Chlamydial infection 6 3
Back pain 6 0
Furuncle 5 6
Flatulence 2 6
Gastroenteritis 2 6
Costochondritis 0 6
Hemorrhoids 0 6
Pruritus 0 6
Grade 2-4 Lab
Abnormality ≥ 5% in Either
Arm, %
BIC + FTC/TAF
(n = 64*)
DTG + FTC/TAF
(n = 32*)
Creatine kinase 13 9
AST 9 3
Hyperglycemia 8 13
ALT 6 0
LDL 6 9
Amylase 5 6
Hematuria 3 6
Glycosuria 2 6
*Pts with ≥ 1 post-BL laboratory assessment, excluding those
not specified for all pts.

32. TMB-301: Long-Acting Ibalizumab in Pretreated
Pts Infected With Multidrug-Resistant HIV
 Ibalizumab: humanized mAb to conformational epitope on CD4 receptor that blocks
postattachment HIV entry into CD4+ T-cells without altering normal cell function
 Single-arm, open-label phase III trial
– Primary endpoint: ≥ 0.5 log10 HIV-1 RNA decrease at Day 14
 53% with resistance to all drugs from ≥ 3 classes; 68% with INSTI resistance
Lewis S, et al. CROI 2017. Abstract 449LB. Slide credit: clinicaloptions.com
Pts with HIV-1 RNA
> 1000 copies/mL;
on ART ≥ 6 mos, on stable
ART ≥ 8 wks; resistant to
≥ 1 ARV from 3 classes,
sensitive to ≥ 1 ARV for OBR
(N = 40)
Wk 25
Ibalizumab
2000 mg IV Day 7
(loading dose)
Continue Failing ART
Days 0-14
Ibalizumab
800 mg IV Day 21, Q2W
(maintenance dose)
Switch to OBR
Day 14
Primary
Endpoint:
Day 14Control Period:
Day 0-7

33. Efficacy, Safety of Ibalizumab Through 24 Wks
 Primary endpoint: 83% with ≥ 0.5 log10
HIV-1 RNA decrease at Day 14 vs 3%
at end of control period (P < .0001)
– 60% with ≥ 1.0 log10 HIV-1 RNA
decrease
– Mean decrease by Day 14: 1.1 log10
 9 pts reported 17 serious AEs
– 1 drug-related serious AE (IRIS)
resulted in discontinuation
 9 other pts discontinued
– Death (n = 4; liver failure, Kaposi
sarcoma; end-stage AIDS,
lymphoma)
– Consent withdrawal (n = 3)
– Lost to follow-up (n = 2)
 No cases of anti-ibalizumab
antibodies
Lewis S, et al. CROI 2017. Abstract 449LB. Slide credit: clinicaloptions.com
Wk 24 Virologic Outcome
Ibalizumab +
OBR
≥ 1.0 log10 HIV-1 RNA decrease, % 55
≥ 2.0 log10 HIV-1 RNA decrease, % 48
HIV-1 RNA < 50 copies/mL, % 43
HIV-1 RNA < 200 copies/mL, % 50
Mean HIV-1 RNA decrease from
baseline, log10
1.6

34. Margolis DA, et al. CROI 2015. Abstract 554LB. Margolis DA, et al. Lancet Infect Dis. 2015;15:1145-1155.
LATTE: Efficacy, Safety of Dual Oral
Cabotegravir + RPV Maintenance Thru Wk 144
Slide credit: clinicaloptions.com
 Dose-ranging, randomized phase IIb study
– Primary endpoint: HIV-1 RNA < 50 c/mL at Wk 48
– At Wk 96:76% of pts receiving CAB + RPV had HIV-1 RNA < 50 copies/mL
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)
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 48:
Primary Endpoint
Wk 24
Induction Phase* Maintenance Phase
Wk 96
CAB 30 mg QD +
RPV 25 mg QD
Open-Label Phase
Wk 144:
Ad Hoc

35. Margolis DA, et al. CROI 2017. Abstract 442. Reproduced with permission. Margolis DA, et al.
CROI 2015. Abstract 554LB. Margolis DA, et al. Lancet Infect Dis. 2015;15:1145-1155.
LATTE: Viral Suppression Continues Through
Wk 144 With Dual Oral CAB + RPV Maintenance
 Ad hoc analysis through Wk 144 of
open-label phase
 Serious AEs: 9%; d/c for AEs: 3%
 PDVF in 9 pts (ITT-E)
– 6 during induction/maintenance
– 3 during open-label (Wks 96-144)
– 2 of 3 had emergent mutations: n = 1
with V151V/I (IN); n = 1 with K101E +
M230M/L (NNRTI)
 1 pt without PDVF developed E138K +
V108V/I (NNRTI)
Slide credit: clinicaloptions.com
Treatment Outcomes at
Wk 144 (Snapshot), n (%)
CAB
Subtotal*
(ITT-E)
(n = 181)
CAB
Subtotal*
(ITT-ME)
(n = 160)
HIV-1 RNA < 50 c/mL 122 (67) 122 (76)
HIV-1 RNA ≥ 50 c/mL
Previous change in ART
18 (10)
3 (2)
13 (8)
2 (1)
No virologic data in window
D/c for AE or death
D/c for other reasons
On study with missing data
in window
41 (23)
8 (4)
27 (15)
6 (3)
25 (16)
4 (3)
15 (9)
6 (4)
PDVF 9 (5) 6 (4)
*CAB 10 mg + CAB 30 mg + CAB 60 mg.

36. CD01 Extension: Long-term, Maintenance PRO
140 Monotherapy Following Initial ART
 PRO 140: humanized IgG4 CCR5
mAb
 Single-arm, open-label phase IIb
extension study[1]
– Maintenance PRO 140 given at 350
mg SC/wk for ≤ 3 yrs in pts stable on
initial ART from CD01 study (N = 16)
 Wkly PRO 140 maintenance SC
injection generally well tolerated
– No drug-related severe AEs or d/c for
AEs
– Infrequent, mild, transient
administration-site reactions in < 10%
of pts
 HIV-1 RNA < 40 copies/mL
maintained in majority of pts
– > 40 wks: 13/16 pts (81.3%)
– > 2 yrs: 10/16 pts (62.5%)
– 1 pt d/c due to relocation; 5 pts had VF
 CD4+ cell counts stable through study
 No anti-PRO 140 antibodies detected
 Ongoing phase IIb/III studies of PRO
140 monotherapy[2]
and in combination
with ART[3]
1. Lalezari J, et al. CROI 2017. Abstract 437. 2. ClinicalTrials.gov. NCT02859961.
3. ClinicalTrials.gov. NCT02483078. Slide credit: clinicaloptions.com

37. Agent
MoA or
Formulation
Phase
Dosing/
Administration
Implications
GS-CA1[1]
HIV capsid inhibitor
Pre-
clinical
Extended release,
suitable for SC of solid
depot formulation
 Potent ART with orthoganol resistance profile to existing
ART; potential for long-acting formulation due to low
aqueous solubility, high stability
GS-9131[2]
NRTI
Pre-
clinical
Potential for once daily
dosing
 Potent ART active against NRTI RAMs K65R, L74V,
M184V alone or in combination; minimal loss of
susceptibility with 4 or more TAMs
MK-8591[3]
Nucleoside Reverse
Transcriptase
Translocation
Inhibitor (NRTTI)
Pre-
clinical
10 mg QW PO; potential
for extended duration
 Comparable MK-8591 levels in animal rectal, vaginal
tissue to TDF levels in tissues of human subjects
highlights potential prophylaxis utility
GS-PI1[4]
PI
Pre-
clinical
Potential for unboosted,
once daily dosing
 Potent ART with high barrier to resistance, including < 2-
fold loss in potency against major PI RAMs, and 10-fold
to 40-fold longer in vivo half life vs ATV or DRV
NANO-EFV,
NANO-LPV[5]
Oral, lower dose
SDN
I
nEFV: 50 mg QD, 21 d
nLPV/RTV: 200/100 mg
BID, 7 d
 Enhanced oral bioavailability suggests can reduce EFV,
LPV dose by ~ 50% while maintaining PK
Additional Investigational Agents Reported at
CROI 2017: Preclinical and Phase I
1. Tse WC, et al. CROI 2017. Abstract 38. 2. White KL, et al. CROI 2017. Abstract 436.
3. Grobler J, et al. CROI 2017. Abstract 435. 4. Link JO, et al. CROI 2017. Abstract 433. 5. Owen A, et al. CROI
2017. Abstract 39. Slide credit: clinicaloptions.com

38. Additional Investigational Agents Reported at
CROI 2017: Phase II
1. Bekker L-G, et al. CROI 2017. Abstract 421LB. 2. Murphy R, et al. CROI 2017. Abstract 452LB.
3. Wang C-Y, et al. CROI 2017. Abstract 450LB. Slide credit: clinicaloptions.com
Agent
MoA or
Formulation
Phase
Dosing/
Administration
Implications
TMC278 LA[1] LA injectable
RPV (IM)
II 1200 mg IM Q8W  Potential as injectable, long-acting PrEP
Elsulfavirine[2]
Prodrug of
new NNRTI
VM1500A
IIb
Combined therapy:
20 mg elsulfavirine
+ FTC/TDF PO
QD
 Less toxic alternative to EFV for initial
ART
UB-421[3] Anti-CD4
receptor mAb
II
10 mg/kg QW IV
or
25 mg/kg Q2W IV
 Possible ART alternative for maintenance
therapy in virologically suppressed pts

39. Treatment Complications and Comorbidities

40. D:A:D: Exposure to ATV/RTV or DRV/RTV and
Risk of CVD
 Prospective analysis of pts followed from
1/1/2009 (BL) to earliest CVD, last visit + 6
mos, or 2/1/2016 (N = 35,711)
– 1157 pts (3.2%) developed CVD (MI, stroke,
sudden cardiac death, invasive CV procedure)
 Cumulative expos. to DRV/RTV, but not
ATV/RTV, assoc. with increased CVD risk in
multivariate analysis: 59% risk increase per 5-
yrs’ DRV/RTV
– Assoc. does not appear to be mediated through
dyslipidemia, in contrast with first-generation PIs
 Limitations: potential for unmeasured
confounding; observational study; unable to
distinguish between DRV/RTV 800/100 mg QD
vs DRV/RTV 600/100 mg BID
Ryom L, et al. CROI 2017. Abstract 128LB. Reproduced with permission. Slide credit: clinicaloptions.com
Relationship Between 5-Yr Exposure to ARVs and CVD
ATV/RTV DRV/RTV
CVD Risk per 5 Yrs of ARV Exposure, IRR (95% CI)
Model ATV/RTV DRV/RTV
Univariate 1.25 (1.10-1.43) 1.93 (1.63-2.28)
Multivariate
 Baseline adjusted* 1.03 (0.90-1.18) 1.59 (1.33-1.91)
 Time-updated
adjusted*
1.01 (0.88-1.16) 1.53 (1.28-1.84)
*Adjusted for: BMI, CKD, DM, CD4, dyslipidemia.
2.5
2.0
1.5
1.0
0.5
0.0CVDIncidenceRate
Ratio(95%CI)
No exposure
Univariate
MV: BL adj model
MV: Time-updated adj
model

41. NA-ACCORD: Smoking, HTN, and Cholesterol
Contribute to MI Risk in HIV Infection
 Retrospective meta-analysis of pts with
validated MI events from 7 clinical cohorts
within NA-ACCORD from 1/2000 to
12/2013 (N = 29,515)[1]
– Population attributable fraction: proportion of
MIs avoidable by prevention of modifiable
HIV-related and traditional MI risk factors
– 347 pts (1.2%) had type 1 MI due to plaque
rupture
– Sensitivity analysis added for 16,687 pts
(57%) with BMI data, 227 had type 1 MI
 ~ 40% MI reduction achievable through
prevention of smoking, elevated TC, or
HTN, regardless of BMI
1. Althoff KN, et al. CROI 2017. Abstract 130. 2. Shepherd L, et al. CROI 2017. Abstract 131. Slide credit: clinicaloptions.com
 In separate study (D:A:D), smoking cessation
reduced overall cancer rate after 1 yr, except
lung cancer (rate high even after > 5 yrs)[2]
*Adjusted for age, sex, race, and all listed risk factors. †
P < .05
Adjusted Population Attributable Fractions
for MI,*[1]
%
MI
BMI
Subgroup
Traditional
MI risk
factors
 Smoking 38†
36
 Elevated TC 43†
39†
 HTN 41†
39†
 All 3 (smoking, TC, HTN) 86
HIV-related
MI risk
factors
 DM 2 4
 CKD 3 3
 CD4+ cell count 10†
14†
 VL 6 8
 AIDS 2 -1
 HCV coinfection 8†
14†

42. clinicaloptions.com/hiv/Retroviruses 2017
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