Cовременное лечение ВИЧ : новые данные с конференции CROI 2017/ Contemporary Management of HIV. New Data From CROI 2017

Contemporary Management of HIV:
New Data From CROI 2017
This program is supported by an independent educational grant from
ViiV Healthcare

Slide credit: clinicaloptions.com
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Program Director and Core Faculty
Program Chair
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
Charles B. Hicks, MD
Professor of Clinical
Medicine
Director, Owen Clinic
University of California, San
Diego
San Diego, California

Faculty Disclosure Information
Joseph J. Eron, Jr., MD, has disclosed that he has
received consulting fees from Gilead Sciences,
Janssen, Merck, and ViiV and funds for research
support from AbbVie, Gilead Sciences, Janssen, and
ViiV.
Charles B. Hicks, MD, has disclosed that he has
received consulting fees from Janssen, Merck, and ViiV
and royalties from UpToDate.

Peer Review Disclosure
Barry S. Zingman, MD
Medical Director, AIDS Center
Clinical Director, Infectious Diseases, Moses Division
Professor of Clinical Medicine, Albert Einstein College
of Medicine
Montefiore Medical Center
The University Hospital for Albert Einstein College of
Medicine
Barry S. Zingman, MD, has no real or apparent
conflicts of interest to report.

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

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, syphilis
rates in short term, concerns
about antibiotic resistance
and long-term safety/efficacy
must be addressed before
consideration of use in
nonresearch setting
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

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 in each mo
following PrEP initiation ranged
from 2-5 per day
– Tested positive for rectal STIs:
gonorrhea (2 x) 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

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

New Data on Initial Treatment
With Currently Available ART

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.
EVG/COBI/FTC/TAF*
single-tablet regimen
(n = 866)
EVG/COBI/FTC/TDF†
(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.

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.
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)
92908785 84
80
4 4 5 4 5 4 4 6
911 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)

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%
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. Slide credit: clinicaloptions.com

Case: HIV-1 RNA Rebound on INSTI
Regimen
 A pt diagnosed with recently acquired HIV infection
presents to you for care
 As part of the initial workup, you order a genotype
resistance test
– The lab calls to ask if you want to include INSTI
resistance testing; you decline this component
 The pt starts treatment with DTG + FTC/TAF
 He tolerates it well and has undetectable HIV-1 RNA
4 mos after starting treatment
 At the 6-mo visit, his HIV-1 RNA is 3400 copies/mL

Case Question: Which of the following is the
most likely reason for the detectable HIV-1 RNA?
A. Previously unrecognized transmitted resistance to
the ART drugs he is taking (DTG + FTC/TAF)
B. Poor adherence to his treatment
C. Drug–drug interactions with the PPI he takes
periodically for heartburn
D. Superinfection with a resistant HIV virus
E. Acquired resistance to DTG

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[1,2]
 CDC National HIV Surveillance System[1]
:
– Prevalence of INSTI resistance for HIV diagnoses through
2014: 65/14,468 (0.4%)
– Transmitted INSTI resistance: 2/4631 (0.04%)
 UNC CFAR HIV Clinical Cohort[2]
:
– 2015 INSTI resistance emergence on treatment in 685 pts
who began ART in 2007 or later: 1%
1. Hernandez AL, et al. CROI 2017. Abstract 478. 2. Davy T, et al. CROI
2017. Abstract 483. Slide credit: clinicaloptions.com

Case Report: INSTI Resistance Emergence
in Acute HIV 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 time point 1 to 20.9% at
time point 3
Fulcher JA, et al. CROI 2017. Abstract 500LB. 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

Case Revisited: HIV-1 RNA Rebound on
INSTI Regimen
 A pt with recently acquired HIV presents to you for care
 As part of the initial workup, you order a genotype resistance
test
– The lab calls to ask if you want to include INSTI resistance testing;
you decline this component
 The pt starts treatment with DTG + FTC/TAF
 He tolerates it well and has undetectable HIV-1 RNA 4 mos
after starting treatment
 At the 6-mo visit, his HIV-1 RNA is 3400 copies/mL
 Upon further discussion with the pt, he notes that he missed
several ART doses during a 2-wk vacation from which he has
just returned

Case: Switching ART in a highly adherent pt with
well-controlled HIV for 6 yrs on DRV/RTV + FTC/TDF
 The pt is seeing you for a regularly scheduled follow-
up visit and mentions he is interested in switching to
an easier ART regimen with as few drugs as possible
because his partner is very concerned that all ART is
“poison” and should be avoided or at least minimized
 He understands that this is not actually true but he
would like to keep his partner happy and asks you
what options are available for him to minimize the
number of drugs he is taking

Case Question: Which of the following
options would you suggest for him?
A. DTG + RPV
B. DTG + 3TC
C. DTG monotherapy
D. I would not feel comfortable prescribing fewer than 3
drugs for ART, and would advise him to change to a
E. I would suggest he wait until there is a single-tablet
regimen of DRV/COBI/FTC/TAF approved for use
F. Something else

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.
Switch to DTG + RPV
(n = 513)
Continue Baseline ART
(n = 511)
HIV-1 RNA < 50 c/mL for
≥ 12 mos while receiving
first or second ART regimen
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

Switch From Suppressive ART to DTG +
RPV Noninferior to Cont. BL 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
Virologic
Nonrespons
eWk 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)

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
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
16.217.1
23.8
19.0
24.023.1
53.0
45.6
55.354.7
P < .001
P < .001
P < .001

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 of ATV/RTV + FTC/TDF in WAVES rerandomized
in current trial[2]
 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
1. 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%

ANRS 167 LAMIDOL: Switch to DTG + 3TC
From Virologically Suppressive 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.
DTG 50 mg QD +
2 NRTI†
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

LAMIDOL Interim Analysis: Switch to DTG +
3TC Maintains 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.
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.

DOMONO: Switch to DTG Monotherapy in
Virologically Suppressed Pts Not Effective
 Randomized comparison of switch to DTG 50 mg QD monotherapy
(immediate switch) vs continued baseline ART for 24 wks followed by
switch to DTG 50 mg QD monotherapy (delayed switch) 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 nonrandomized 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

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

Investigational Antiretroviral
Drugs

Doravirine or Darunavir + RTV Both With 2
NRTIs in Treatment-Naive Pts
 Doravirine: next-gen NNRTI, unique resistance profile, low DDI
potential, no food or PPI effects
 Multicenter, randomized, double-blind phase III trial
14-day
follow-up
Molina 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

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
Virologic
Nonrespons
e
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)

Doravirine vs DRV + RTV in Combination
With FTC/TDF or ABC/3TC: Safety
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.

Bictegravir + FTC/TAF vs DTG + FTC/TAF
in Treatment-Naive Pts
 Bictegravir: investigational 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
Open-
label
extension
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)

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
Sax PE, et al. CROI 2017. Abstract 41.
Virologic
Failure
Wk 48
Virologic
Success
No Data
100
80
60
40
20
0
97
91
2 6 2 3
(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
(95% CI: -8.5% to 14.2%)
BIC + FTC/TAF (n = 65) DTG + FTC/TAF (n = 33)

 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
Sax PE, et al. CROI 2017. Abstract 41.
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.

TMB-301: Long-Acting Ibalizumab for
Pretreated 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.
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

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.
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

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
 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
*Pts with HIV-1 RNA < 50 c/mL at Wk 24 continued to maintenance phase.

FTC/TDF or ABC/3TC.
CAB 10 mg QD +
RPV 25 mg QD
CAB 30 mg QD +
RPV 25 mg QD
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)
(n = 60)
(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

Margolis DA, et al. CROI 2017. Abstract 442. Margolis DA, et al. CROI
2015. Abstract 554LB. Margolis DA, et al. Lancet Infect Dis.
2015;15:1145-1155.
LATTE: Viral Suppression Thru 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)
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.

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 (N = 16)[1]
– In initial study, pts stable on initial
ART switched to maintenance PRO
140 monotherapy 350 mg SC/wk (N
= 42)
– 17 pts with maintained viral
suppression for 13 wks trained to
self administer wkly PRO 140 SC
and offered continued monotherapy
in extension study: N = 16 enrolled
in extension
 CD4+ cell counts stable through
study
 No anti-PRO 140 Abs detected
 Wkly PRO 140 maintenance SC
injection generally well tolerated
– No drug-related severe AEs or d/c
for AEs
– Infrequent, mild, transient injection-
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 (relocation); 5 pts had VF
 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

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)
I
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, QD 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

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.
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

Treatment Complications and
Comorbidities

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
 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.
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.
Relationship Between 5-Yr Exposure
to ARVs and CVD
ATV/RTV DRV/RTV
2.5
2.0
1.5
1.0
0.5
0
CVDIncidenceRate
Ratio(95%CI)
No exposure
Univariate
MV: BL adj model
MV: Time-updated adj model

NA-ACCORD: Smoking, HTN, Cholesterol
Primary Drivers 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  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]
1. Althoff KN, et al. CROI 2017. Abstract 130. 2. Shepherd L, et al.
CROI 2017. Abstract 131.
*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†

Case: ART and Coronary Artery Disease
 Pt is a 53-yr-old man with well-controlled HIV on
DRV/COBI + FTC/TAF
– CD4+ cell count: 654 cells/mm3
(32%)
– He tolerates his ART well and is extremely adherent
 He is concerned that his medications may increase his risk
of a heart attack and asks if he should switch his ART
regimen
 He smokes 1 pack per day
 He has borderline hypertension; most recent BP was
142/88 mm Hg
 Most recent LDL: 132 mg/dL

Case Question: Which of the following
strategies would you recommend for this pt?
A. Referral to smoking cessation
B. Nutrition counseling
C.Enhanced antihypertensive therapy
D.Switch of his ART away from boosted DRV therapy
E. A-C only
F. A-D

Key Take-home Points
 Greater experience with PrEP has enhanced our
knowledge base
– We now know PrEP failure can occur even in highly
adherent persons, although it appears to be rare
– Regular HIV serology assessment is essential and unusual
seroconversion patterns are possible
 STIs are common among persons taking PrEP, probably
reflecting inconsistent condom use
– Best management approaches to deal with this issue are
being determined, but use of patient-initiated antibacterial
therapy requires more study before it can be advocated

Key Take-home Points
 INSTI-based ART is now mainstay of initial HIV treatment
– Transmitted INSTI resistance is exceptionally uncommon to
date
 Switching ART to simpler, better-tolerated regimens is
now a well-established management strategy
– Results with switch to DTG plus a second agent are
promising, but switch to DTG monotherapy is ineffective,
with frequent virologic failure often with significant INSTI
resistance, and should not be done in clinical practice
 New antiretroviral drug development remains an active
area of clinical research and new drugs in all current
classes appear promising, as do agents with new
mechanisms of action

Go Online for More CCO
Coverage of HIV!
Additional slidesets on contemporary management of HIV with expert
faculty commentary
Postconference clinical updates available following CROI, the
International AIDS Conference, and IDWeek
clinicaloptions.com/hiv

Cовременное лечение ВИЧ : новые данные с конференции CROI 2017/ Contemporary Management of HIV. New Data From CROI 2017

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