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Slide1
Highlights for clinical practiceHIV
International Congress of Drug Therapy in HIV
Infection
Glasgow
, UK
23-26
October
2016Slide2
About the slide deck
Goal
How
to
reach
the
goal?Slide3
Structure of slide deckSlide4
DisclaimerThis scientific
material
was prepared
by e-HIMS; content selection and review was performed by
:
Dr. Eric Florence, ITG
Antwerp
(editorial board)
Dr.
Agnès
Libois
, CHU St Pierre, Brussels (
medical
reporter)
Dr. Charlotte Martin, CHU St Pierre, Brussels (
medical
reporter)
Dr. Eric Van Wijngaerden, UZ-
KULeuven
, Leuven (editorial board)
The
information
on the slides included is
not intended to replace professional guidelines or established clinical
practice
Concerning medical treatment options, the approved summary of product characteristics should be used for
guidanceSlide5
Disclaimer – terms of use
©
2016
These slides may not be published or posted online without permission from the publisher
e-HIMS (request by email info@e-hims.com)The slides may be re-used in personal presentations and in meetings organised by the industry partner with a license agreement (
ViiV
Healthcare Belgium), upon appropriate referencing to the source as ‘Derived from FORUM HIV - 2016
©
e-HIMS
’Slide6
Overview PEP/
PrEP
Diagnosis
Co-
morbidities & ageing
ARV
safety
Treatment
simplification
Switch
strategies
C
o-
infections
New
ARVsSlide7
PEP/PrEPSlide8
InterPrEP: internet-based PrEP with generic
TDF/FTC in London – analysis of PK,
safety
and outcomesWang X. J Int AIDS Soc 2016;19(Suppl
7
):15(
abs.O315)Slide9
Are drug concentrations of bioequivalent generic forms of TDF/FTC consistent
with
the
FDA-approved TDF/FTC for PrEP?
FDA-
and
WHO-
approved
forms
of TDF/FTC are
available
via
the
internet (eg
www.iwantprepnow.co.uk
)
There
are concerns
about
the
authenticity
of
medicines
purchased
onlineSlide10
Population and assessments
Population
characteristics
N=234MSM (%)
100
Median
age
(
yr
)
37
Chemsex
(%)
35
PrEP
dosing
schedule
(% pts)Event-driven: 15% Daily: 85%CompanyCipla: N=181Emcure: N=2Mylan: N=1Not reported: N=50Online supplierswww.iwantprepnow.co.uk: 92%www.alldaypharmacy.co.uk: 6%Other: 2%
Plasma TFV/FTC therapeutic drug monitoring in 234 HIV-negative individuals on generic PrEPEvaluation of renal function at baseline and every 3 monthsHIV and STI testing at baseline and every 3 months
Wang X. J Int AIDS
Soc
2016;19(
Suppl
7):15(
abs.O315
)
– poster & oral presentationSlide11
TFV
FTC
Median
(
ng/mL)103
142
Range (
ng
/
mL
)
21-597
17-1,876
Median
time post
dose
(h)
15.5
15.5
N=212
Plasma concentrationsRepeated for 12 individuals: adequate plasma concentrations of TFV non-TDF and FTC No HIV infections observed (FU on N=201)Normal renal function at baseline and FUOutcomeWang X. J Int AIDS Soc 2016;19(Suppl 7):15(abs.O315) – poster & oral presentation
PharmacokineticsEfficacy and safetySlide12
Are drug concentrations of bioequivalent generic forms of TDF/FTC consistent with
the
FDA-approved
TDF/FTC for PrEP?In this
cohort
there
appears
to
be
no concerns
about
the
pharmacokinetic
properties
of generic TDF/FTC purchased onlineSlide13
Risk perception in MSM taking PrEP
Boccino
S.
J Int AIDS Soc
2016;19(Suppl 7):28(abs.P012)Slide14
How does PrEP influence risk perception of MSM?
PrEP
is
recommended
in adults at high risk of acquiring HIV infection when
condoms
are
not
used
consistently
PrEP
does
not
protect
against
other STIs and should be used in combination with other preventive interventionsSlide15
SurveyMSM attending a central London
sexual
health
clinic for
PrEP monitoring (Febr-June 2016)Self-reported anonymous paper questionnaire
Boccino
S. J Int AIDS
Soc
2016;19(
Suppl
7):28(
abs.P012
)
Completed
questionnaires (N)
100
MSM
respondents
(N)
100PrEP adherence (%)DailyEvent-driven Not specified77194Median time on PrEP (mo)3
83% more relaxed about
risk of
acquiring
HIVSlide16
Change in
self-reported
condomless sexual activity
Boccino S. J Int AIDS Soc 2016;19(Suppl 7):28(
abs.P012)
*2
pts
no data on
PrEP
duration
*Slide17
How does PrEP influence risk perception of MSM?
T
here
appears to be an association
between
length
of time on
PrEP
and
increased
condomless
sexual
activity
MSM taking
PrEP seem less afraid about acquiring HIV but less so about acquiring other STIsSlide18
Compliance of fixed-dose single tablet EVG/COBI/FTC/TDF regimen vs LPV/r / d4T/3TC for
PEP in
sexual
assault
victims: a retrospective sequential period study
De Wit S.
J Int AIDS
Soc
2016;19(
Suppl
7
):27(
abs.P010)Slide19
Is PEP compliance in sexual assault victims higher
with
a single-tablet versus a
multi
-tablet regimen?Although PEP is often recommended
in
sexual
assault
cases, compliance is
poor
(~40%)
A single-tablet PEP regimen showed high levels of adherence and completion in a recent studySlide20
Retrospective sequential period analysis (2011-2015)
Prospective
PEP
registry
Compliance = pts taking PEP for 28 dExtracted
from
medical
records
Calculated
from
pharmacy
records
De Wit S. J Int AIDS
Soc
2016;19(
Suppl
7):27(
abs.P010
) – posterVariableValueReceived PEP / Consulted for PEP (N)283/368Female (%)92Migrants (%)50Mean age (yr)27Exposure (%)Vaginal receptive
Anal receptiveOral receptive842927Slide21
Compliance for PEP in
sexual
assault
victimsDe Wit S. J Int AIDS Soc 2016;19(Suppl 7):27(abs.P010) –
poster
ComplianceSlide22
Is PEP compliance in sexual assault victims higher with a single-tablet versus a
multi
-tablet regimen?
Switching to a well-tolerated single-pill regimen
(EVG/COBI/FTC/TDF) does not seem to significantly improve compliance in sexual assault victimsSlide23
DiagnosisSlide24
Targeting HIV testing at a population level: cost-effectiveness of three
approaches
Gomez
Ayerbe
C. J Int AIDS Soc 2016;19(Suppl 7):230-2(abs.P328)Slide25
What is the most cost-effective targeted HIV testing
approach
to
predict
HIV infection?Targeted HIV testing
by
filling
in a
self-administered
Risk Exposure &
Clinical
Indicators (RE&CI) questionnaire
and
testing
only
subjects
with
a positive questionnaire seems as efficient as a non-targeted routine testing in the DRIVE 01 studySlide26
Study
design: non-
targeted
HIV
testing programme in the emergency
department
and
primary
care
centre
-
DRIVE 01
study
Gomez
Ayerbe
C.
J Int AIDS
Soc
2016;19(Suppl 7):230-2(abs.P328) – poster*being at increased risk of HIV infectionSlide27
Population characteristics (N=5,329)
Sens
Spec
PPV
NPV
Routine
testing
as
ref
RE&CI questionnaire
100
49
1
100
DHRS
73
60
1
100
HIDES
91
741100Women: 50%Median age: 37 yrPositive …
RE&CI questionnaire: 52%DHRS: 40%HIDES: 27%NHD confirmed by enzyme immunosassay/western blotting 0.4%Gomez Ayerbe C. J Int AIDS Soc 2016;19(Suppl 7):230-2(abs.P328) – poster
Predictive
performance of
targeted
HIV tests
NHD/MHI
N
tests
avoided
N test
for
1 pos
result
Routine
testing
22/0
0
242
RE&CI questionnaire
22/0
2,601
124
DHRS
16/6
3,212
132
HIDES
20/2
3,948
69
NDH: new HIV diagnosis; MHI:
missed
HIV
infections
Slide28
Cost
and
cost-effectivenessGomez Ayerbe C. J Int AIDS
Soc
2016;19(
Suppl
7):230-2(
abs.P328)
– posterSlide29
What is the most cost-effective targeted HIV testing approach to
predict
HIV infection?
While the RE&CI questionnaire detected
all
HIV-
infected
subjects
from
the
routine
strategy
,
the
HIDES test
seems
to
avoid the highest number of tests and has a high sensitivity as wellSlide30
Co-morbidities & ageing Slide31
Cognitive function and depression in HIV-positive
individuals
and
matched controlsDe Francesco D. J Int AIDS Soc
2016;19(
Suppl
7):
10-1(
abs.O215)Slide32
Is there an association between
cognitive
function
and depression in HIV patients?
Cognitive
disorders
and
depression
remain
prevalent in HIV
ptsSlide33
*
matched
for gender,
ethnicity, sexual orientation and location
Study
design:
multi-centre
,
prospective
,
observational
study
-
POPPY
De Francesco D.
J Int AIDS
Soc
2016;19(
Suppl
7):10-1(abs.O215) – oral presentationSlide34
Baseline characteristics
Depression
outcome
De Francesco D. J Int AIDS
Soc
2016;19(
Suppl
7):10-1(
abs.O215
)
– oral presentation
Variable
HIV
pts
≥50
yr
(N=637)
HIV
pts
<50 yr(N=340)Controls ≥50 yr(N=276)Male (%)898165White (%)888191Median age (yr)56
4358MSM (%)807250Viral load <50 c/mL9286-Median CD4 count
(
cells
/µL)
620
654
-
Previous
/
current
alcohol drinker (%)
13/80
10/81
7/88
Previous
/
current
smoker
(%)
38/22
28/28
40/14
Recreative
drug
use
(%)
26
34
15
PHQ-9: score 0-4 none, 5-9 mild, 10-14 moderate, 15-27 severe
depression
Slide35
Cognitive function outcomeDe Francesco D.
J Int AIDS
Soc
2016;19(Suppl
7):10-1(abs.O215) – oral presentation
Difference
in
median
score*
HIV
pts
≥50
yr
vs
controls
≥50
yr
HIV pts <50 yr vs controls ≥50 yrGlobal Z-scorePoorer cognitive score; P=0.003Poorer cognitive score; P=0.06Multivariate analyses*
Difference in median global Z-score; PAlcoholYears of drinking (per 5 yr-increase)Positive; P=0.02
Smoking
Current
/ex-
smoker
vs
never
smoked
Not
significant
Use
of
marijuana
Yes
vs
no
Not
significant
Depression
Any
vs
no
Negative
;
P
<0.05
Association
cognitive
function
with
lifestyle factors
*
adjusted
for
age
, gender,
ethnicity
and
educationSlide36
Is there an association between cognitive
function
and depression
in HIV patients? HIV pts seem
to
have
poorer
cognitive
scores
compared
to
controls
,
which
appears
associated with depressionSlide37
Neuro+3 study: cognitive evolution in HAND after 96 wk of treatment intensification with higher CNS penetration score
Force G.
J Int AIDS
Soc 2016;19(
Suppl 7):161(abs.P217)Slide38
Does treatment intensification with higher CNS penetration
score
improve
cognitive
results in virologically controlled pts?
HIV infection
can
result
in neurocognitive disorders (HAND)
Some
reports suggest that the use of
ART
with good
CNS
penetration leads to better neurocognitive outcomesSlide39
†Grooved Pegboard, Verbal
Fluency
, CVLT, Digit span, PASAT, Digit
symbol
, Wisconsin Card Scoring Test (6 domains)*Exclusion criteria: drug/alcohol abuse,
HBsAg
or HCV
positivity
,
hypothyroidism
,
vitamin
B
deficiency
,
psychiatric
problems
Study
design: Open-label pilot
study
Force G. J Int AIDS Soc 2016;19(Suppl 7):161(abs.P217) – poster63 pts screened in 8 investigational centres31 pts included
*ARV changed to new combination with higher CNS penetration
effectiveness
(CPE)
(≥3 point score
improvement
and
total
score
of
≥9)
Raw
test score
Global deficit score
Cognitive
Complaint
Questionnaire score
HAND level
classification
≥2
ability
domains
altered
†Slide40
Tx intensification with INSTI (64.5%), CCR5 inhibitor (32.3%) or NNRTI (19.4%)
Force G. J Int AIDS
Soc
2016;19(
Suppl 7):161(abs.P217) – posterEvolution of
cognitive
results
(N=31)
HAND
classification
(N=31)
*7
pts
with
one
altered
domain
**2 pts with one altered domain and 3 pts with normal tests
ImprovemntSlide41
Does treatment intensification with higher CNS penetration score improve
cognitive
results in virologically
controlled pts?Treatment intensification
by
NNRTI, INSTI
and
/or CCR5 inhibitor
seems
to
be
associated
with
a
statistical
improvement in cognitive test after 48 and 96 weeks, with enhanced GDS and HAND classificationSlide42
The relative impact of ARV drugs and baseline immune status on bone quality
in
HIV-positive
subjects: results
from the HIV UPBEAT cohortMcGinty T.
J Int AIDS
Soc
2016;19(
Suppl
7
):130-1(
abs.P169)Slide43
What is the effect of HIV-specific factors on bone microstructure
?
In
pts
with similar bone
mineral
density
(BMS),
the
trabecular
bone
score (TBS)
can
non-
invasively
detect
differences in bone qualityHIV-positive subjects have a lower TBS compared with HIV-negative persons, which appears to be driven by current smoking statusSlide44
Study designN=201 HIV-positive patients
from
HIV UPBEAT cohort
BMD: measured by dual X-ray absorptiometry (DXA)
TBS:
derived
from
baseline
lumbar
spine
DXA images
using
TBS
Insight
software
McGinty
T. J Int AIDS
Soc
2016;19(Suppl 7):130-1(abs.P169) – poster & oral presentation Baseline characteristicsValueMean age (yr)39Male (%)59.2Duration HIV disease (yr)4.5
Nadir/current CD4 count (cells/mm³)211/471Cumulative ART exposure (yr)2.7Current smoker (%)35.8Homosexual/heterosexual
sex/IVDU
(%)
31/52/17Slide45
Variable
Effect on
TBS
95% CI
P
Current
smoker
-0.047
-0.085, -0.008
0.02
Nadir CD4
count
(per 50
cells
/mm³
higher
)
0.005
0.003, 0.011
0.04
PI-
containing ART-0.045-0.079, -0.0110.009ResultsMcGinty T. J Int AIDS Soc 2016;19(Suppl 7):130-1(abs.P169) – poster & oral presentation Multivariate analysis* - final model that best predicts lower TBS in HIV-positive pts
Patient characteristics significantly affecting TBSTDF treatment status did not affect TBS
*
Adjusted
for
lumbar
spine
BMD,
ethnicity
,
age
, gender, BMI
and
current
smoking status Slide46
What is the effect of HIV-specific factors on bone microstructure
?
In
addition
to smoking, also baseline immune status and exposure to
PI (
rather
than
TDF)
seem
significantly
associated
with
lower
TBS
and
related bone quality in HIV-positive subjectsSlide47
HIV patients today
and
10
yr
ago: do they have the same needs? Results
from
cross-
sectional
analysis of ANRS CO3 Aquitaine cohort
Bonnet F.
J Int AIDS
Soc
2016;19(
Suppl
7
):9(
abs.O212)Slide48
What is the evolution of chronic non-HIV-related
diseases
and
risk factors over 10 yr?People living with HIV live
longer
due
to
effective
ART
Due
to
ageing
, risk factor exposure, ART
and
HIV-
related factors, HIV-infected people are more likely to develop co-morbidities Slide49
Study
design:
longitudinal
cross-sectional
study of the prospective ANRS CO3 Aquitaine cohort
Bonnet F. J Int AIDS
Soc
2016;19(
Suppl
7):9(
abs.O212
) – oral presentationSlide50
HIV and ART characteristics (N=2,138)
2004
2014
Male
71%
Median
age
(
yr
)
42
52
Age >50
yr
20%
62%
Median
BMI
22
23
MSM40%Heterosexual33%Bonnet F. J Int AIDS Soc 2016;19(Suppl 7):9(abs.O212) – oral presentationPopulation characteristics (N=2,138)
ART drug class (% pts)200420142 NRTIs + 1 PI/r
24
32
2
NRTIs
+ 1 NNRTI
22
32
2
NRTIs
+ INTI
0
7
Other
tx
35
26
No
tx
19
3Slide51
Bonnet F. J Int AIDS Soc 2016;19(Suppl 7):9(abs.O212) – oral presentation
Significant (
P
<0.0001)
increase
over 10
yr
:
Co-
morbidities
, co-
treatments
and
risk scores
Tobacco
use
(~
40
%)
and
antidepressant drug use (~ 10%) stable over 10 yrSlide52
What is the evolution of chronic non-HIV-related diseases
and
risk factors over 10 years?
Significant improvement in HIV markers over 10 yearsHigher prevalence
of co-
morbidities
over time,
especially
dyslipidaemia
and
hypertension
,
with
increased
associated
risk factors and co-treatmentsSlide53
Future challenges for clinical care of an
ageing
population
infected with HIV: a “geriatric HIV” modelling study
De Francesco D.
J Int AIDS
Soc
2016;19(
Suppl
7
):118-9(
abs.P155)Slide54
How will the HIV population evolve
and
what are
the implications?According to a modelling study, multimorbidity
in HIV patients will be
the norm
15 years from now
Frailty, geriatric
syndromes and disability will be relevant clinical
outcomes in this contextSlide55
*Model follows pts enrolled up
to
2015
and
generates new entries on a yearly basis up to 2030 with the
relationship
between
age
, gender,
geriatric
syndrome
and
disability
being
constant over time
**Housekeeping, money management, cooking, transportation, telephone use, shopping, laundry, medication managementIndividual-based model of ageing HIV population - ItalyDe Francesco D. J Int AIDS Soc 2016;19(Suppl 7):118-9(abs.P155) – posterFrailty index = Proportion of deficits present (total of 37)<0.3: not frail0.3-0.4: frail≥0.4: most frailData from Modena
HIV Metabolic Clinic collected between 2009-2015*N=2,982
Geriatric syndrome
= Patient-reported fall frequency in the past year (≥1)
Disability
= Impairment in ≥1 IADL**Slide56
Model outcomesDe Francesco D. J Int AIDS Soc 2016;19(Suppl
7):118-9(
abs.P155
)
Population
characteristics
HIV-positive
pts
2015
2030
Median
age
(
yr
)
49
59
>50 yr (%)4295
Frailty indexFrail (%)Most frail (%)2624
28
48
Geriatric
syndrome
(%)
NA
30
Disability
(%)
NA
34Slide57
How will the HIV population evolve and
what
are the
implications?The increasing number of older patients with frailty, geriatric syndromes and disability seems to depict a ‘geriatric HIV’ scenario in 15 years
Tailored
screening and clinical protocols adapted to a geriatric
hiv
population are
neededSlide58
Quantifying the future clinical burden
of
an
ageing
HIV-positive population in Italy: a mathematic modelling study
Smit M.
J Int AIDS
Soc
2016;19(
Suppl
7
):119-20(
abs.P156)Slide59
What is the forecast of age and non-communicable
disease
burden
amongst HIV-positive pts on ART in Italy?
HIV-positive
people
are at
higher
risk of
suffering
from
age-related
non-
communicable
disease
(NCDs) compared to uninfected personsCountry-specific estimates of future NCD burden need to be developed to guide HIV policiesSlide60
*Large cohort of
42
Italian
infectious disease centres
Smit M. J Int AIDS
Soc
2016;19(
Suppl
7):119-20(
abs.P156
) – posterSlide61
Population
characteristics
HIV-positive pts
on ART
2015
2035
Mean
age
(
yr
)
46
59
>50
yr
(%)
30
76
NCDs
None (%)≥3 (%)CVD* burden (%)36105711
46
85
Drivers of
rising
NCD
burden
: CVD*, CKD
and
diabetes
*
Hypertension
,
dyslipidaemia
,
stroke
or
myocardial
infarction
Model
outcomes
Smit M. J Int AIDS
Soc
2016;19(
Suppl
7):119-20(
abs.P156) –
posterSlide62
What is the forecast of age and non-communicable
disease
burden
amongst HIV-positive pts on ART in Italy?Italian HIV-positive
patients
on ART seem to age and are likely to suffer from an increasing NCD burden, especially from CVDSlide63
Epidemiologic “snapshot” of the HIV-positive population in Belgium, 2014
to
2016
Callens S.
J Int AIDS Soc 2016;19(Suppl 7):129-30(abs.P167)Slide64
How is the current Belgian HIV population
composed
and
what is the prevalence of the main
non-
infectious
co-
morbidities
?
HIV care in Belgium:
11 AIDS
reference
centres
and
7 HIV
reference
laboratories
in Belgium 14,000 HIV cases in 2014; 3 new cases per day Of HIV individuals diagnosed in 2006-2008: 98.2% linked to care and 90.8% retained in HIV careSlide65
Cross-sectional analysis of cohort data4 Belgian HIV
reference
centres
N=5,785 HIV-positive individuals with ≥1 FU care (June 2014 –
July
2016)
Callens S. J Int AIDS
Soc
2016;19(
Suppl
7):129-30(
abs.P167
) – poster
Baseline
characteristics
Value
Mean
age
(
yr)46.6Female (%)37.6Mean nadir/recent CD4 count (cells/mm³)268.8/651.3Started HIV treatment (%)94.9Risk factorsSmokers, former or current (%)
Hypertension (%)HCV-RNA positive (%)37.917.43.1Slide66
All
ages
(N=5,785)
≤40
yr
41-50
yr
51-60
yr
≥60
yr
Diabetes mellitus
5.9
1.8
4.5
10.4
12.2
CVD*
2.9
0.6
1.5
4.9
8.3
CKD
7.7
1.7
5.3
10.6
24.9
Other
**
0.8
0.4
0.6
1.7
0.9
Outcomes
NCIMs
Callens S. J Int AIDS
Soc
2016;19(
Suppl
7):129-30(
abs.P167) –
poster
Confirmed
eGFR
<60 mL/min/1.73 m² when baseline
eGFR
>60, or
Confirmed 25%
eGFR
decline when baseline
eGFR
<60
Myocardial infarction
Cerebrovascular accident, or
Invasive cardiovascular procedure
Clinical diagnoses, or
Prescription of anti-diabetic drugs or insulin
*Data
from
3
centres
**
Anal
cancer
and
Hodgkin’s
lymphomaSlide67
How is the current Belgian HIV population composed
and
what is the
prevalence of the main non-infectious co-morbidities?
Almost
40% of
the
HIV-
infected
population
is ≥50
years
Higher
prevalence
of
NICMs
,
especially
CKD and diabetes mellitus in the elderly, warrants the need for careful patient managementSlide68
ARV safetySlide69
Higher rates of neuropsychiatric adverse events leading to
DTG
discontinuation
in women
and older ptsSabranski
M.
J Int AIDS
Soc
2016;19(
Suppl
7
):10(
abs.O214)Slide70
Is there a need for concern about
potential
neuropsychiatric adverse events
related to DTG?Recent reports
of DTG have
raised
concerns
about
the
safety
of DTG in real-life
practice
with
regard
to
neuropsychiatric AEsSlide71
Study
design:
retrospective
analysis of HIV pts
from 2 German centres
Sabranski
M.
J Int AIDS
Soc
2016;19(
Suppl
7):10(
abs.O214
) – oral presentationSlide72
Total
discontinuation
rate: 9%
Reasons:Discontinuation rate on DTG
Sabranski
M.
J Int AIDS
Soc
2016;19(
Suppl
7):10(
abs.O214) – oral presentation
N=985,
median
FU 11.5 mo (range 0-25.4 mo)
Estimated
AE
discontinuation
rate
at 12 mo5% neuropsychiatric AEs: mostly insomnia, sleep disturbances No hospitalisation for symptoms;
quick disappearance of symptoms after discontinuationSlide73
Multivariate Cox regression
analysis
RH (95% CI)
P
Female vs male
2.64 (1.23-5.65)
0.0122
>60
yr
vs
younger
2.86 (1.42-5.77)
0.0033
ABC
with
DTG
initiated
vs no ABC2.42 (1.38-4.24)0.002DTG start in 2016 vs 2014/511.36 (4.31-29.41)<0.0001No association with ethnicity, centre, CD4 cell count, prior AEs with other ARTsNeuropsychiatric symptoms reproducible in 6 cases upon re-exposure to DTG86% of DTG discontinuers had no tolerability
problems with the subsequent ART (FU >3 mo)Variables associated with DTG discontinuation due to neuropsychiatric AEsSabranski M. J Int AIDS Soc 2016;19(Suppl 7):10(abs.O214) – oral presentation
Likely
due
to
increased
awareness of
treating
physiciansSlide74
Is there a need for concern about potential
neuropsychiatric
adverse events
related to
DTG?In this retrospective cohort
study
,
the
DTG
tx
discontinuation
rate
due
to
neuropsychiatric
AEs is relatively high (6% at 12 mo)Women, older pts and pts on ABC co-initiation tx had a 2-3 fold higher risk of DTG tx discontinuation due to neuropsychiatric AEsThese AEs were reversible and not severe (mostly sleep disturbances)Slide75
Psychiatric AEs from the DTG ART-naïve
phase
III clinical
trialsQuercia R. J Int AIDS Soc 2016;19(Suppl 7
):155-6(
abs.P210)Slide76
Does DTG have psychiatric side effects in treatment-naïve subjects?INSTIs are one of the classes recommended for pts starting ART due to their favourable safety and tolerability profile
Psychiatric
AEs
(pAEs) have been reported in INSTI-treated pts, but at lower
frequency
than
in EFV-
treated
ptsSlide77
Data analysisPhase III/IIIb trials in t
x-naïve
subjects on DTG 50 mg q
d with ≥48 wk of data as of April 2016SPRING-2, FLAMINGO, SINGLE studies: 96 wk FU data
ARIA
study
: 48
wk
FU data
N=1,315
with
DTG
Quercia
R. J Int AIDS
Soc
2016;19(
Suppl
7):155-6(
abs.P210
) – poster & oral presentation
*Defined according to MedDRApAEs* grouped in 5 categoriesSlide78
pAEs
(N=2,634)
Quercia
R. J Int AIDS
Soc 2016;19(Suppl 7):155-6(abs.P210) – poster & oral presentation
*
Values
<1Slide79
% of
AEs
SPRING-2
FLAMINGO
SINGLE
ARIA
DTG*
(N=411)
RAL*
(N=411)
DTG*
(N=242)
DRV/r*
(N=242)
DTG
†
(N=414)
EFV
‡
(N=419)
DTG
§
(N=248)ATV/r
‡
(N=247)
Insomnia
Drug
related
(%)
Severe or
grade
3/4 (%)
24
0
15
0
20
0
31
0
61
4
54
0
50
10
13
0
Anxiety
Drug
related
(%)
Severe or
grade
3/4 (%)
6
6
9
0
8
0
0
0
14
0
37
10
0
0
13
25
Depression
Drug
related
(%)
Severe or
grade
3/4 (%)
3
3
10
5
0
19
0
8
37
14
43
18
11
0
9
9
Suicidality
Drug
related
(%)
Severe or
grade
3/4 (%)
0
75
0
83
25
75
0
0
0
67
57
71
33
0
0
25
Characteristics
of
pAEs
Quercia
R. J Int AIDS
Soc
2016;19(
Suppl
7):155-6(
abs.P210) – poster & oral
presentation
Co-
medication
with
*2NRTIs;
†
ABC/3TC;
‡
TDF/FTC;
§
DTG/3TC
Majority
of
pAEs
were
low
grade
and
few
leading
to
tx
discontinuationSlide80
Does DTG have psychiatric side effects in treatment-naïve subjects?
DTG once daily
seems to be
well tolerated with a low rate of
pAEs, the majority of which were low grade, as reported from clinical trialsSlide81
Treatment simplification Slide82
Non-inferiority of dual therapy with
DRV/r + 3TC
vs
triple therapy
with DRV/r + TDF/FTC or ABC/3TC for maintenance of viral suppression: 48-wk results
of
the
DUAL-GESIDA 8014 trials
Pulido
F.
J Int AIDS
Soc
2016;19(
Suppl
7
):16-7(
abs.O331)Slide83
Is dual therapy with DRV/r + 3TC non-inferior
to
triple
therapy
with DRV/r + 2 N(t)RTIs for maintenance of virological suppression
?
Dual
therapy
with
a
boosted
PI
and
3TC
can
have
advantages
in
toxicity
and costDual therapy with 3TC and LPV/r or ATV/r is non-inferior to triple therapy with 2 N(t)RTIs and LPV/r or ATV/r for maintaining virological suppressionSlide84
Primary endpoint: % of pts
with
HIV-RNA <50 c/
mL at
wk 48 cfr FDA snapshot algorithm in exposed ITT population
Secondary
endpoints
:
% of
pts
with
HIV-RNA <50 c/
mL
at
wk
48
cfr
FDA snapshot algorithm in PP and observed therapy populations% pts with persistently suppressed viraemia, % pts with blipsSafetyStudy design: Multi-centre, open-label, non-inferiority RCT Pulido F. J Int AIDS Soc 2016;19(Suppl 7):16-7(abs.O331) – poster & oral presentation
Switch to dual therapy: DRV/r qd + 3TC qd48 wk; N=129Suppressed HIV patients
HIV-RNA <50 c/
mL
for
>6 mo
On triple
therapy
with
DRV/r + ABC/3TC or TDF/FTC ≥2 mo
No
resistance
to
DRV, 3TC or FTC
HBsAg
negative
Continue triple therapy:
DRV/r
qd
+ ABC/3TC or TDF/FTC
48
wk
; N=128Slide85
Baseline characteristics similar between groups
Primary
endpoint
: non-inferiority at
wk
48
Male (83%)
100
wk
with
suppressed
viraemia
(
median
)*
CD4 nadir 246
cells
/mL (median)TDF/FTC use at baseline (75%)ABC/3TC use at baseline (25%)Pulido F. J Int AIDS Soc 2016;19(Suppl 7):16-7(abs.O331) – poster & oral presentationSimilar results for PP and observed therapy populations
*80 vs 113 wk for dual vs triple therapy (P=0.014)Slide86
Secondary
endpoints
– no significant difference
Pulido F. J Int AIDS Soc 2016;19(Suppl 7):16-7(
abs.O331
) – poster & oral presentation
Viral
load
suppression
(<50 c/
mL
in
all
visits
)
Blips
* in
pts
with HIV-RNA <50 c/mL at wk 48*transient viral load ≥50 c/mLSlide87
Safety of
dual
vs
triple therapyPulido F. J Int AIDS Soc 2016;19(Suppl
7):16-7(
abs.O331
) – poster & oral presentation
Pts
(%)
Dual (N=126)
Triple (N=123)
Any
AE
Grade 2
or 4
Any
grade
3 or 4 lab AE
70
12376153SAE55Discontinuation due to
AE or intolerance12AEs occurring in ≥10% of pts (% pts)Dual
(N=126)
Triple (N=123)
Respiratory
25
24
Infections
and
infestations
18
15
Digestive
14
18
Muscular
or
skeletal
13
18
Neuropsychiatric
10
10
No
statistically
significant
difference
between
groups
No
statistically
significant
difference
between
groupsSlide88
Is dual therapy with DRV/r + 3TC non-inferior to triple
therapy
with DRV/r + 2 N(t)RTIs
for maintenance of virological suppression?
Dual
therapy
with
DRV/r + 3TC
seems
non-
inferior
(
and
as well
tolerated
) as DRV/r + TDF/FTC (or ABC/3TC)
for
maintenance of
virological
suppression over 48 wkSlide89
Switching from cART to DTG maintenance monotherapy
in
virologically
suppressed
HIV-1 infected adults: a randomised, multi-centre, non-
inferiority
clinical
trial (DOMONO)
Wijting I.
J Int AIDS
Soc
2016;19(
Suppl
7
):17-8(
abs.O333)Slide90
Is DTG monotherapy non-inferior to cART in
maintaining
virological
suppression?DTG in cART shows equal
or superior
virological
suppression
vs
NNRTI, PI or first-
generation
INSTI in
cART
Given
potential
side
effects
of
cART, maintenance therapy with fewer drugs is warrantedOnly retrospective studies have investigated DTG maintenance monotherapySlide91
Primary endpoint: virological suppression
at 24
wk
(% pts
with HIV-RNA <200 c/mL) for DTG vs
continuous
cART
Secondary
endpoints
:
Virological
suppression
at 24
wk
(%
pts
with
HIV-RNA <50 c/mL)% pts on DTG immediate+delayed monotx with virological suppression at 24 and 48 wkStudy design: Multi-centre, open-label, non-inferiority RCTWijting I. J Int AIDS Soc 2016;19(Suppl 7):17-8(abs.O333) – poster & oral presentation
Immediate DTG monotherapy (50 mg qd)48 wk, N=51cART patients HIV-RNA <50 c/mL
for
>6 mo
HIV-RNA
zenith
<100,000 c/
mL
CD4
cells
nadir >200
cells
/mm
3
No
resistance
, no
virological
failure
HBV-immune or
vaccinated
>95%
estimated
compliance
Continue
cART
24
wk
, N=53
Delayed
DTG monotherapy (50 mg
qd
)
48
wk
On-treatment analysis:Slide92
Baseline characteristics
Non-
inferiority
Wijting I. J Int AIDS
Soc
2016;19(
Suppl
7):17-8(
abs.O333) –
poster & oral
presentation
Variable
DTG
(N=51)
cART
(N=53)
Male (%)
92
91
MSM transmission (%)
8077
On TDF
before
switch (%)
86
85
Median
time on
cART
(mo)
35
43
Median
HIV-RNA
zenith
(c/
mL
)
22,000
28,000
Median
CD4 nadir (
cells
/µL)
320
380
Primary endpointSlide93
Secondary endpoints
Wijting I. J Int AIDS
Soc
2016;19(
Suppl
7):17-8(
abs.O333) –
data from poster & oral presentations included Slide94
Virological
failures
(>50 c/
mL at wk 24) – secondary endpoint
Wijting I. J Int AIDS
Soc
2016;19(
Suppl
7):17-8(
abs.O333) –
data from poster & oral presentations included
At
wk
24:Slide95
Is DTG monotherapy non-inferior to cART in maintaining
virological
suppression
?In a carefully selected
HIV
population
on
suppressive
cART
,
switching
to
DTG maintenance
monotherapy
:
Seems
to
be non-inferior to cART in virological suppression <200 copies/mL at 24 wkTends to provide more often lower level viraemias than cART continuation at 24 wkSlide96
Long-term use of DRV/r qd monotherapy in daily
practice
:
retrospective
observational cohort data of 111 HIV pts in BelgiumDe Wit S. J Int AIDS
Soc
2016;19(
Suppl
7
):108-9(
abs.P137)Slide97
Is DRV/r qd monotherapy a suitable option for virologically suppressed pts?
DRV/r 800 mg/100 mg qd in combination therapy with other ARVs, but not as monotherapy, is recommended as first-line option
Clinical trials have shown the usefulness of DRV/r monotherapy for pts with stable virological suppression on cARTSlide98
Study design:
Multi-centre
, retrospective, observational cohort study in Belgium
De Wit S. J Int AIDS Soc 2016;19(Suppl 7):108-9(
abs.P137) – posterSlide99
Baseline characterstics (N=111)
Variable
Value
Age (yr)
49.5Male (% pts)
65.8
CD4 cells/mm
3
(mean)
648.1
CD4 nadir
(mean)
223.0
HIV-RNA (% pts)
<50 c/mL
50<200 c/mL
84.7
7.2
De Wit S. J Int AIDS
Soc
2016;19(
Suppl 7):108-9(abs.P137) – posterPrimary endpoint: 25.2% of pts discontinued Tx (median follow-up of 2.6 yr)Slide100
Secondary endpoints
De Wit S. J Int AIDS Soc 2016;19(Suppl 7):108-9(
abs.P137) – posterSlide101
Is DRV/r qd monotherapy a suitable option for virologically suppressed pts?Based on long-term real-life data in a Belgian subpopulation, DRV/r qd monotherapy seems to have good efficacy and tolerability in virologically suppressed patientsSlide102
Dual therapy with a boosted PI plus 3TC is an
effective
maintenance
strategy in
pts on 2nd-line ART in Africa: the ANRS 12286/MOBIDIP trial
Ciaffi
L
.
J Int AIDS
Soc
2016;19(
Suppl
7
):5(
abs.O122)Slide103
Is addition of 3TC a good strategy to
increase
efficacy of
the maintenance strategy with PI/r, without additional toxicity
?
PI-
based
2
nd
-line ART is
effective
in low resource
countries
BUT long-term
toxicities
,
costs
and
saving future options request for tx simplification maintenance strategiesPI monotherapy maintenance tx may lead to viral escape and low level viraemiaSlide104
Primary
endpoint
:
% pts with tx failure (viral
load ≥500 c/
mL
confirmed
with
1 mo interval,
reintroduction
of 2
NRTIs
,
interruption
of PI/r)
Study
design:
multi-centre
, African, randomised, open-label superiority trial – ANRS 12286 MOBIDIPCiaffi L. J Int AIDS Soc 2016;19(Suppl 7):5(abs.O122) – oral presentation FTC + TDF + LPV/rANRS 12169 2LADY>48 wk, N=454ABC +
ddI + LPV/rLPV/r monotxANRS 12286 MOBIDIP96 wk
, N=265
FTC + TDF + DRV/r
LPV/r + 3TC
DRV/r
monotx
DRV/r + 3TC
Included
in MOBIDIP
if
:
Viral
load ≤200 c/
mL
for
≥6 mo
No
change in ART in last 3 mo
CD4
≥100
cells
/
mL
Adherence
≥90% at end of 2LADY trial
PI/r
(N=133)
PI/r + 3TC (N=132)Slide105
Baseline characteristicsAnalysis at 48 wk due
to
premature stop of monotx
armPrimary endpoint (ITT):
Ciaffi
L
. J Int AIDS
Soc
2016;19(
Suppl
7):5(
abs.O122
) – oral presentation
Variable
PI/r
(N=133)
PI/r + 3TC
(N=132)
Median
age (yr)4143Women (%)7670Viral load <50 c/mL (%)8083Median CD4 (cells/µL)498472PI = DRV (%)
4233M184V at 1st-line tx failure (%)9597
Pts
with
PI/r
PI/r + 3TC
Virological
failure
28
3
Reintroduction
NRTI
for
other
reasons
2
0
Death
/lost
to
FU
3
1
Total*
33
4
*
All
had
viral
load
<
200 c/
mL
in
median
10
wk
after
reintroduction
of NRTI backboneSlide106
No tx
discontinuations
due
to intoleranceSafety and
tolerability
at 48
wk
Ciaffi
L
. J Int AIDS
Soc
2016;19(
Suppl
7):5(
abs.O122
) – oral presentation
AE
Renal
and
lipid profilePts withPI/r(N=133)PI/r + 3TC(N=132)Severe AE (%)1310AIDS-defining events (%)52Tuberculosis (N)20Slide107
Is addition of 3TC a good strategy to increase
efficacy
of
the maintenance strategy
with PI/r, without additional toxicity?
After
virological
suppression
with
PI plus
NRTIs
in 2
nd
-line
tx
in
limited
resource settings, maintenance with PI/r plus 3TC seems associated with a higher rate of success than PI/r monotherapySlide108
Simplification to ATV/r + 3TC vs maintaining ATV/r + 2 NRTIs in virologically suppressed HIV-infected pts: 96-wk data of the ATLAS-M trialGagliardini
R. J Int AIDS
Soc
2016;19(Suppl
7):4-5(abs.O121)Slide109
Is switching virologically suppressed HIV pts
to
dual
therapy of ATV/r + 3TC non-inferior to continuing triple therapy
of ATV/r + 2
NRTIs
in
terms
of long-term
efficacy
?
Tx
simplification
strategies
aim
to
improve adherence, long-term tolerability to ART and reduce costs while maintaining virological efficacyDual tx showed superior efficacy vs triple therapy in a post-hoc analysis of the ATLAS-M trial at 48 wkSlide110
Primary endpoint: % pts free from
tx
failure* at wk
48 in ITT populationSecondary endpoint: non-inferiority
(
margin
-12%) of %
pts
free
from
tx
failure*
at
wk
96
in ITT
population
Study design: 96-wk, phase IV, Italian multi-centre, open-label RCT (ATLAS-M)Gagliardini R. J Int AIDS Soc 2016;19(Suppl 7):4-5(abs.O121) – poster & oral presentationContinue ATV 300/r 100 + 2 NRTIs = triple tx96 wk; N=133Suppressed adult HIV patients HIV-RNA <50 c/
mL for ≥6 moCD4 >200 cells/mm3 for ≥6 moOn therapy
with
ATV/r +2
NRTIs
for
≥3 mo
No
previous
virological
failures
No
previous
mono/
dual
ART
No
known
resistance
to
ATV or 3TC
No
HBsAg
+
No
pregnancy
No PPI
Switch to ATV 300/r 100 + 3TC 300 = dual
tx
96
wk
; N=133
*
defined
as
modification
/
discontinuation
of
tx
for
any
cause
and
/or
virological
failure (2
viral
loads >50 c/
mL
or single
value
>1,000 c/
mLSlide111
Baseline characteristics
Variable
Triple
tx
(N=133)Dual
tx
(N=133)
Median
age
(
yr
)
44
44
Male (%)
75
84
TDF-
containing
backbone (%)
8478Median CD4 (cells/µL)616622Mo with viral load <50 c/mL2124Comparable tx groups:Gagliardini R. J Int AIDS Soc 2016;19(Suppl 7):4-5(abs.O121) – poster & oral presentation
Free of tx failure* at 96 wkSimilar results in the PP population
Trend of
lower
virological
failure (as
cause
of
tx
failure)
for
dual
vs
triple
tx
:
1.5%
vs
6.8% of
pts
–
P
=0.06
CD4
cell
count
:
in
cre
ase
over 96
wk
but no significant
difference
between
groups
*
defined
as
modification
/
discontinuation
of
tx
for
any
cause
and
/or
virological
failure (2
viral
loads >50 c/mL or single value >1,000 c/mLSlide112
Safety Gagliardini R. J Int AIDS Soc 2016;19(
Suppl
7):4-5(
abs.O121) – poster & oral presentation
Evolution of lipid profile and bilirubine
Evolution
of
renal
safety
8
renal
colics
occurred
: 6 in triple
tx
and
2 in dual txSlide113
Is switching virologically suppressed HIV pts to
dual
therapy of ATV/r + 3TC non-inferior
to continuing triple therapy of ATV/r + 2 NRTIs in
terms
of long-term
efficacy
?
At 96
wk
,
switching
to
dual
therapy
vs
continuing triple therapy in virologically suppressed HIV pts seems:Non-inferior and even superior in terms of tx failureAssociated with improved renal function and worsened lipid levelsSlide114
Resistance profile analysis of tx-experienced HIV-1 infected pts switching
to
EVG/COBI/FTC/TAF plus DRV
Margot N. J Int AIDS Soc 2016;19(Suppl 7):5
-6(
abs.O123)Slide115
Is there an influence of the
ART
regimen
or the
resistance profile on the outcome of tx
simplification
in
virologically
suppressed
tx-experienced
pts
on complex
regimens
?
In
the
study GS-US-292-0119, 94% versus 76% of the virologically suppressed, tx-experienced pts on complex multi-tablet regimens maintained suppressed when switched to EVG/COBI/FTC/TAF+DRV versus when staying on the DRV-containing baseline regimenSlide116
Primary endpoint: % pts
with
HIV-RNA <50 c/
mL at
wk 24 (FDA snapshot analysis)Secondary endpoints: Safety
and
tolerability
over 24
and
48
wk
Efficacy
at
wk
48: HIV-RNA <50 c/
mL
Study
design:
multi-centre
,
phase III, open-label switch randomised study – GS-US-292-0119Margot N. J Int AIDS Soc 2016;19(Suppl 7):5-6(abs.O123) – poster & oral presentation EVG/COBI/FTC/TAF+DRV 800 mg qd (SR)96 wk, N=89Virologically suppressed HIV pts
≥4 mo suppressed on ART with DRV≥2 prior failures≥2-class resistance
by
historical
genotype (no INSTI-
resistance
or
currently
on INSTI)
K65R or
≤3
TAMs
Exclude
: Q151M, T69ins, DRV
RAMs
Baseline regimen (BR)
48
wk
, N=46
EVG/COBI/FTC/TAF+DRV
8
00 mg
qd
(SR)
48
wk
2:1Slide117
Baseline characteristics
SR (N=89)
BR (N=46)
Median
CD4
count
(
cells
/µL)
519
518
Median
N of
pills
/d
5
5
2/3
classes
resistance (%)70/2674/20≥2 classes resistance (%)PINNRTINRTI358895ResistanceK65R≤3 TAMs2044TDF/ABC/
other NRTI (%)61/11/1254/11/13RAL (%)5650Margot N. J Int AIDS Soc 2016;19(Suppl 7):5-6(abs.O123) – poster & oral presentation
Primary
endpoint
–
wk
48
Switching
to
SR
was non-inferior/superior to staying on BRSlide118
Virological suppression was similar in each arm,
regardless
of DRV
dosage at baseline
Switching to SR was statistically superior to staying on BR
Switching
to
SR
was
non-inferior/statistically superior
to
staying on BR
Outcome
at
wk
48 –
influence
of baseline factors
Margot N.
J Int AIDS
Soc 2016;19(Suppl 7):5-6(abs.O123) – poster & oral presentationDRV dosage at baselineGenotypic Sensitivity Score (GSS)GSSSlide119
Is there an influence of the ART regimen or
the
resistance profile on the
outcome of tx simplification in virologically suppressed tx-experienced
pts
on complex
regimens
?
Strategic
simplification
of
tx-experienced
pts
taking
~5
pills
/d
to EVG/COBI/FTC/TAF+DRV (2 pills qd) was statistically superior in virological suppression to staying on baseline regimen, regardless of baseline DRV dose or GSS Slide120
Efficacy of antiretroviral drugs during intermittent maintenance treatment
with
a 4-days-a-week
regimen
despite low plasma concentrations (ANRS 162-4D trial)Alvarez JC. J Int AIDS Soc
2016;19(
Suppl
7
):69(
abs.P081)Slide121
Is it feasible to maintain
virological
suppression
with an intermittent tx regimen?
An
intermittent
tx
regimen
could
be
an
alternative
for
HIV pts who have to take medication all life-longSlide122
Primary
endpoint
: virological
suppression at wk 48
Study
design:
Prospective
multi-centre
, open-label, single-arm,
48-wk French
study
with
4-consecutive
days
on
tx
- 3 days off tx strategy Alvarez JC. J Int AIDS Soc 2016;19(Suppl 7):69(abs.P081) – posterSlide123
Baseline characteristics (N=100)
Variable
Value
Median
age (yr
)
47
Median
d
uration
of
virological
suppression
(<50 c/
mL
,
yr
)4.0Baseline ART regimen TDF + FTC (N)ABC + 3TC (N)ABC + TDF (N)2 NRTIs + NNRTI (%)EFVETVRPV2 NRTIs + PI/rDRVATVLPV89101714052629
15131Alvarez JC. J Int AIDS Soc 2016;19(Suppl 7):69(abs.P081) – posterSlide124
Plasma concentrations over 48 wk with intermittent
regimen
Alvarez JC. J Int AIDS
Soc 2016;19(Suppl 7):69(abs.P081) – poster
Efficacy
cut-off
High
adherence
:
Questionnaire: 95-100% in >90%
pts
MIMSCaps
(N=26
pts
): 100% in
dosage
timing 4-d-a-wk
for
median
44 of 51 wk per patientON: 4-consecutive days on tx – OFF: 3 days off txSlide125
Is it feasible to maintain virological
suppression
with an
intermittent tx regimen?
A
lmost
all
pts
with
UNDETECTABLE
viraemia
remained
virologically
suppressed
at 48
wk
when applying a 3-d tx interruption on a 4-d-a-wk regimen, despite low plasma concentrations of PIs or NNRTIs, especially in off periods Slide126
Switch strategiesSlide127
Long-term (96-wk) efficacy and safety after
switching
from TDF
to TAF in HIV-infected, virologically suppressed adults
Raffi
F.
J Int AIDS
Soc
2016;19(
Suppl
7
):6-7(
abs.O125)Slide128
Is FTC/TAF non-inferior to FTC/TDF to maintain virological suppression in combination with a variety of 3rd agents on the long term?
A recent
study
has shown similar efficacy of FTC/TAF vs FTC/TDF with other 3
rd agents, albeit with less renal and bone toxicities, over 48 wkSlide129
Primary endpoint: HIV-RNA <50 c/mL at 48 wkSecondary endpoints:
HIV-RNA
<50 c/mL at
96
wkSafety and tolerability
Study design: Double-blind/double-dummy RCT
Raffi F. J Int AIDS Soc 2016;19(Suppl 7):6-7(
abs.O125
) – oral & poster presentation
FTC/TAF
qd
* +
FTC/TDF placebo
qd
+
Continue 3
rd
agent
96
wk
; N=333
Suppressed HIV patients HIV-RNA <50 c/mL On therapy with FTC/TDF + 3rd agenteGFR ≥50 mL/min
FTC/TDF qd +FTC/TAF placebo qd* +Continue 3rd
agent
96
wk
; N=330
*Dose: 200/10 mg with boosted PI;
200/25 mg with unboosted 3
rd
agentSlide130
Baseline characteristics
Variable
FTC/TDF
(N=330)FTC/TAF(N=333)
Female (% pts)
16
14
Median CD4
count
(
cells
/mm
3
)
624
663
Median
eGFR
(mL/min)
10099Median duration on FTC/TDF (yr)5.05.2Boosted PI as 3rd agent (% pts)4547Raffi F. J Int AIDS Soc 2016;19(Suppl 7):6-7(abs.O125) – oral & poster presentationSimilar results when stratified by 3rd
agent (boosted PI vs other)No emergent resistance except one FTC/TAF pt (M184V at wk 36)Virological suppressionSlide131
Raffi F. J Int AIDS Soc 2016;19(Suppl 7):6-7(abs.O125) - poster
Safety – 96 wk follow-up
Raffi F. J Int AIDS Soc 2016;19(Suppl 7):6-7(
abs.O125)
–
oral & poster presentation
Safety and tolerability
Markers of renal, bone and lipid safety
Pts
(%)
FTC/TDF
(N=330)
FTC/TAF
(
N=333)
Discontinuations
due to AEs/total
1/12
2/11
Grade 3-4 lab abnormalitiesLDL 2652910
AEs (>10% of pts)URT infectionDiarrhoeaNasopharyngitisCough20128615
13
12
11
Drug-related SAE
0.3
0
Pts
(%)
FTC/TDF
(N=330)
FTC/TAF
(
N=333)
P
Median
change in
eGFR
(mL/min)
+4
+10
<0.001
Mean % change in bone mineral density
Spine
Hip
-0.2
-0.3
+2.2
+1.9
<0.001
<0.001
Median LDL (
mmol
/L)
2.93
3.3
<0.001
Total
cholesterol:HDL
ratio
3.6
3.8
0.09Slide132
Is FTC/TAF non-inferior to FTC/TDF to maintain virological suppression in combination with a variety of 3rd agents on the long term?
In virologically suppressed pts switching from FTC/TDF to FTC/TAF, suppression seems to be
maintained
over 96 wk, while renal and bone parameters improved Slide133
Co-infectionsSlide134
Prevalence and predictors of HPV infection at oral
cavity
and
anal site: findings in an Italian anal
cancer
screening
programme
for
HIV-positive
males
Garbuglia
AR.
J Int AIDS
Soc
2016;19(
Suppl
7):173(abs.P237)Slide135
What is the prevalence and which
are
the
associated
risk factors of HPV infection in the oral cavity in HIV-positive
men?
HIV-infected men carry an increased risk of HPV-associated
infection
Information
for appropriate allocation of
cancer screening
as well as vaccination
programs
is
neededSlide136
Cross-sectional study
Patient
characteristics
ValueMedian
age
(
yr
)
44.6
Mode of HIV
acquisition
(%)
Homo-/bi-
sexual
Heterosexual
Other
/
unknown
85.29.84.9Median CD4 count (cells/mm³)701HIV-RNA (%)Not detectableDetectable <40 copies/mL≥40 copies/mL73.115.211.7On cART (%)94.7
Paired oral rinse and anal samples from HIV-positive males from anal screening programTested with 2 primer sets for HPVN=264 HPV positive samples typed byCLART2 HPV assay (
Genomica
) or
Direct
sequencing
Garbuglia
AR. J Int AIDS
Soc
2016;19(
Suppl
7):173(
abs.P237
) – posterSlide137
Oral
HPV-
HPV+
Anal
HPV-
13.3%
1.8%
HPV+
64.3%
20.5%
Prevalence
of HPV
infection
at
oral
cavity
and
anal
siteGarbuglia AR. J Int AIDS Soc 2016;19(Suppl 7):173(abs.P237) – poster
12.5% of pts with HPV- anal sites have HPV oral infection24.1% of pts with HPV+
anal
sites have HPV
oral
infection
P
=0.10
Total: 100%
N=59
N=224Slide138
Multivariable regression
analysis
OR (95% CI)
P
Age (<45 yr
vs
>45
yr
)
1.5 (0.8-2.9)
NS
Drug
use
(
current
vs
no/
former
)
1.1 (0.5-2.5)
NSSmoking (current vs no/former)1.5 (0.8-2.9)NSNumber of lifetime partners 10-99 vs <10>100 vs <102.7 (0.4-17.0)8.5 (1.4-53.6)NS<0.05HIV-RNADetectable <40 c/
mL vs neg>40 c/mL vs neg1.1 (0.5-2.6)2.1 (0.8-5.4)NSNSCD4 count (<200 vs >200 cells/mm³)
14.6 (2.1-104.4)
<0.05
HPV at
anal
site (yes
vs
no)
1.7 (0.6-4.7)
NS
Risk factors for
oral
HPV
infection
Garbuglia
AR. J Int AIDS
Soc
2016;19(
Suppl
7):173(
abs.P237) –
posterSlide139
What is the prevalence and which are the
associated
risk factors of HPV infection i
n the oral cavity in HIV-positive men?
In
HIV-positive
pts
,
prevalence
of HPV
infection
in
the
oral
cavity
was
significantly
lower than observed at anal siteSevere immune depression and sexual history, but not anal infection, seem to be associated with increased oral HPV infectionSlide140
TURQUOISE-I part 2: safety and efficacy of ombitasvir +
paritaprevir
/r ±
dasabuvir
with or without RBV in pts with HIV-1 and HCV GT1 or 4 co-infection
Rockstroh
J.
J Int AIDS
Soc
2016;19(
Suppl
7
):179-80(
abs.P248)Slide141
What is the efficacy and safety
profile of 3D ± RBV in HIV/HCV GT1
pts
and
2D in HIV/HCV GT4 pts, with(out) compensated cirrhosis and
with
HIV
virological
suppression
?
OBV + PTV/r + DSV
= 3 direct-acting-antiviral (3D
) regimen ±
RBV approved
for HCV
GT
1
infection
OBV +PTV/r + RBV = 2 direct-acting-antiviral (2D) approved for HCV GT4 infectionSlide142
Primary endpoint: N and % of pts achieving
SVR12 (HCV-RNA <
lower
limit of quantitation
[LLOQ])Other endpoints: on-tx virological failure
and
post-
tx
relapse, maintenance of HIV
suppression
,
AEs
/lab
abnormalities
,
resistance
analyses
for
failures
Study
design: Phase III, multi-centre, global, randomised study – TURQUOISE-I part 2Rockstroh J. J Int AIDS Soc 2016;19(Suppl 7):179-80(abs.P248) – posterHIV/HCV GT 1 or 4 pts18-70 yrHCV tx-naïve or -experienced with pegIFN/RBV or SOF + RBV ±
pegIFNHIV-RNA <40 c/mLStable ART: ATV/r, DRV/r, RAL, DTGNo HBsAg+Good blood/renal/liver values
GT1 (N=200)
(with*)out cirrhosis
GT4 (N=28)
No cirrhosis
3D
3D + RBV*
2D
3D*
3D + RBV
3D + RBV*
Wk
12
Wk
24 Slide143
Baseline characteristicsRockstroh J. J Int AIDS Soc 2016;19(
Suppl
7):179-80(
abs.P248) – poster
Variable
GT1
N=200
GT4
N=28
Median
age
(yr)
50
47
Male (% pts)
78
93
Cirrhosis
(%)
12
0HCV tx-naïve (%)6761ART regimen (%)DRV/rATV/rRALDTG-2547282972539
Efficacy: SVR12*includes
pts
missing data as
virological
failures
**
excludes
non-
virological
failures
and
pts
missing data
3
pts
no SVR12: 1 on-
tx
virological
failure, 2 relapsesSlide144
Outcome – 12 wkRockstroh J. J Int AIDS
Soc
2016;19(
Suppl 7):179-80(
abs.P248) – posterMaintenance of HIV suppression in HIV/GT1+4
Safety/
tolerability
*
All
pts
with
HIV-RNA <200 c/
mL
AE (%)
GT1
N=200
GT4
N=28
Any
AE8586AEs leading to tx discontinuation00Serious AE54
Common AE (≥10% pts)FatigueNauseaDiarrhoeaHeadacheInsomniaPruritusHgb decrease242116
14
15
11
10
18
18
4
18
7
4
14Slide145
What is the efficacy and safety profile of 3D ± RBV in
HIV/HCV
GT1
pts
and 2D in HIV/HCV GT4 pts, with(out) compensated
cirrhosis
and
with
HIV
virological
suppression
?
99% overall SVR12
rates
were
achieved
in HIV/HCV GT1 pts following tx with 3D ± RBV and HIV/HCV GT4 pts on 2D, without impact on HIV controlOver 12 wk, the regimen was well tolerated with no hepatic decompensation and no tx discontinuations due to AEsSlide146
SOF/VEL single-tablet regimen in HCV mono-infected and HIV/HCV co-infected
pts
: comparison of
efficacy and safety data from phase III
clinical
trials
Wyles
D.
J Int AIDS
Soc
2016;19(
Suppl
7
):187-8(
abs.P259)Slide147
Does the SOF/VEL single-tablet regimen show a similar efficacy and
safety
profile in HCV vs
HIV/HCV co-infected pts?12-wk
oral
SOF/VEL single-tablet regimen (400/100 mg
qd
) has
demonstrated
high SVR in HCV GT 1-6
pts
Previous
SOF-
based
combinations
showed
a
comparable efficacy/safety profile in HCV vs HIV/HCV co-infected ptsSlide148
Primary endpoints:SVR12
Discontinuations
due
to AEsStudy design:
D
escriptive
analysis of
phase
III 12-wk studies
Wyles
D. J Int AIDS
Soc
2016;19(
Suppl
7):187-8(
abs.P259
) – poster
SOF/VEL N=624
ASTRAL-1
GT 1, 2, 4-6
12 wkHCVPlacebo N=116
SOF/VEL N=134ASTRAL-2GT 212 wkHCV
SOF+RBV N=132
SOF/VEL N=277
ASTRAL-3
GT 3
12
wk
SOF/VEL
24
wk
SOF+RBV
HCV
SOF+RBV N=275
SOF/VEL N=106
ASTRAL-5
GT 1-4
12
wk
HIV/HCV co-infection
Tx
experienced
(28%);
cirrhosis
(21%)
Tx
experienced
(29%);
cirrhosis
(18%)
*HIV:
stable
ART –
various
ART
regimens
!
mean
CD4
count
598
cells
/µLSlide149
SVR12
outcome
of SOF/VEL:
total
and based on GTWyles D. J Int AIDS
Soc
2016;19(
Suppl
7):187-8(
abs.P259) –
poster
ASTRAL 1-2-3: HCV mono-
infected
pts
ASTRAL 5: HIV/HCV co-
infected
pts
35
41
N1,035328238277
116No influence of presence of baseline NS5A class RAVs on SVR12 outcome in either patient group
5
12
11
12
N
106
66Slide150
Pts (%)
SOF/VEL HCV
(N=1,035)
SOF/VEL HCV/HIV
(N=106)
Placebo
(N=116)
SOF+RBV 12-wk
(N=132)
AE
Grade 3
or 4
79
3
71
8
77
<1
77
2
SAE**
2*2*02AE leading to tx discontinuation<122
0Death<1*000Safety of SOF/VEL (retrospective integrated analysis)No pt
with
confirmed
on-
tx
HIV
virologic
rebound
Type of most common
AEs
(>10%) of SOF/VEL
were
similar
to
placebo:
headache
,
fatigue
, nausea, insomnia,
nasopharyngitis
No impact of SOF/VEL on
renal
function
,
irrespective
of TDF
use
Wyles
D. J Int AIDS
Soc
2016;19(
Suppl
7):187-8(
abs.P259) –
poster
*none
were
assessed
as
related
to
study
tx
; **SAE: acute
radial
nerve
palsy
and
left
toe
infection
/sepsis/UTISlide151
Does the SOF/VEL single-tablet regimen show a similar efficacy and safety profile in HCV
vs
HIV/HCV co-
infected
pts?SOF/VEL appears to
result
in a
similarly
high % SVR12 in mono-
infected
vs
HIV/HCV co-
infected
pts
(
across
all
HCV
genotypes)Tx with SOF/VEL for 12 wk seems safe and well tolerated in HIV/HCV co-infected pts on various ART regimensSlide152
Liver fibrosis regression in HIV-HCV co-infected individuals after
sustained
virologic
response with HCV direct-acting antivirals
Arias
A.
J Int AIDS
Soc
2016;19(
Suppl
7
):197-8(
abs.P276)Slide153
How is liver fibrosis evolving after sustained
virological
suppression in HIV-HCV co-infected pts who were
treated
with
HCV direct-
acting
antivirals
?
HCV eradication with
peginterferon
-ribavirin
was
shown to be associated with significant improvements in
liver function
and
fibrosis Information on the extent of liver fibrosis regression is lacking in HIV-HCV co-infected individuals in whom hepatic fibrosis more rapidly developsSlide154
*
Defined
as:
Shift
from advanced fibrosis (metavir
F3-4, >9.5 kPa)
to
null
-mild fibrosis (F0-2)
and
/or
>30%
reduction
on kPa
from
any
baseline
value
Study: Single-centre, prospective study in SpainArias A. J Int AIDS Soc 2016;19(Suppl 7):197-8(abs.P276) – posterSlide155
Pt characteristics (N=50)Liver
fibrosis
outcome
Male 79%
Mean age 52
yr
HCV
viral
count
6.2 log UI/
mL
IL28B no CC 53%
DAA
therapy
:
SOF-LVP N=31
3D N=8
SOF-DCV N=8
SOF-SMV N=8
Mean
tx duration 12 wkPts receiving RBV 54%Arias A. J Int AIDS Soc 2016;19(Suppl 7):197-8(abs.P276) – posterBaselineResultsF3-F4 liver fibrosis65% (80% for IL28B-CC vs 52% IL28-CT/TT, P=0.04)FibroScan value20.1 kPa
At time of SVR12ResultsLiver fibrosisSign. regression in 39% vs baselineMean reduction in FibroScan value vs baseline
4.8
kPa,
P
<
0.001
%
pts
with
sign
.
improvements
in
liver
fibrosis
47% of F3-4
pts
vs
22% of F0-2
pts
,
P
=0.08Slide156
How is liver fibrosis evolving after sustained virological
suppression
in HIV-HCV co-infected
pts who were treated with HCV direct-
acting
antivirals
?
HCV treatment
with
DAA in HIV-HCV co-
infected
pts
seems
associated
with
significant and rapid improvements in liver fibrosis (38% at SVR12)Slide157
Hepatitis C can be cured for
less
than $100 per person: analysis of drug exports
from IndiaHill A. J Int AIDS Soc 2016;19(Suppl
7
):182(
abs.P251)Slide158
Is it theoretically possible to manage hepatitis C at low
cost
?
Novel
direct-acting antivirals (DAA) for chronic hepatitis C achieve sustained
virologic
response rates
of >90
%
But high drug
prices
limit access
to
DAAsSlide159
Study
: data analysis of online database of Indian export
ledgers
Hill A. J Int AIDS Soc 2016;19(Suppl 7):182(
abs.P251
)Slide160
DAA
Export volume
from
India (kg)
~ N of 12-wk coursesMean API
price
/kg ($)
Theoretical
target
price
per 12-wk
tx
($)
US
price
per 12-wk
tx
– x-
fold
target
priceSOF10,200 ~ 303,000 courses1,09462804-1,355DCV5,443 ~ 1,080,000 courses998143,618-4,500LDV240 ~ 32,000 courses2,44134SOF+LDV
96591-984VEL-8,900-11,700119-154SOF+VEL181-216346-413
UK, Germany
and
France are in
the
top 3
countries
(out of 7-9)
with
the
highest
price
for
12-wk courses
with
SOF
and
with
DCV (
based
on
selected
literature
data)
Results
Hill A. J Int AIDS
Soc
2016;19(
Suppl
7):182(
abs.P251
)Slide161
Is it theoretically possible to manage hepatitis C at low cost?
HCV
DAAs
tx costs could be
very
low in
principle
,
when
using
APIs
exported
from
India,
and
still include a 50% profit margin for generic suppliersSlide162
New ARVsSlide163
The integrase strand transfer inhibitor bictegravir has a long integrase/DNA dissociation half-lifeWhite K. J Int AIDS Soc
2016;19(
Suppl
7):36(abs.P025)Slide164
Does bictegravir have longer dissociation kinetics compared
to
other
INSTIs?Bictegravir is a HIV INSTI with a high barrier to resistance selection
in
vitro
Potent ARV
activity
and a
higher genetic barrier to
resistance have been predicted to correlate with a longer dissociation rate constantSlide165
Measure ³H-labelled INSTIs with wild-type HIV integrase
/DNA
complexes
and
scintillation proximity assay:Exponential decay: apparent
association
and
dissociation
kinetics
*Equilibrium binding model: t
1/2
more
representative
of
actual
t
1/2
by converting
initial values of the dissociation rate constants (k
off)Pharmacokinetics of bictegravir and other INSTIsWhite K. J Int AIDS Soc 2016;19(Suppl 7):36(abs.P025)P=0.0018
P=0.046Slide166
Does bictegravir have longer dissociation kinetics compared to
other
INSTIs?
Bictegravir has the longest reported
dissociation
half-life
from
wild-type HIV
integrase
/DNA
complexes
compared
to
dolutegravir
,
elvitegravir
and raltegravirSlide167
Efficacy and safety of long-acting HIV fusion inhibitor albuvirtide in ARV-experienced adults with HIV-1: interim 48-wk results from the randomized, controlled, phase III, non-inferiority TALENT
study
Wu
H.
J Int AIDS Soc 2016;19(Suppl 7):21-2(abs.O336)Slide168
What is the efficacy and safety
profile of
albuvirtide
+ LPV/r in ARV-
experienced adults with HIV-1?Slide169
Primary endpoint: % pts with plasma viral
load <50 c/
mL
at wk
48 (non-inferiority margin of 12%)Study design: Multi-centre
, open-label,
phase
III, non-
inferiority
RCT in China - TALENT
Wu
H.
J Int AIDS
Soc
2016;19(
Suppl
7):21-2
(abs.O336
) – oral presentation
Adults
with HIV-1failing 1st-line treatment:plasma viral load >1,000 c/mL >6 moABT* + LPV/r bid (N=210)LPV/r + TDF/ZDV+3TC (N=210)
48 wk* Once weekly
by
iv
infusionSlide170
Baseline characteristics Interim analysis –
Primary
endpoint
(mITT
population
)
Wu
H.
J Int AIDS
Soc
2016;19(
Suppl
7):21-2
(abs.O336) – oral
presentation
Variable
ABT
(N=83)
NRTI
(N=92)
Age (yr)4040Male (%)7473HIV-RNA (log10 c/mL)3.83.8CD4 count (cells/µl)240234Time of 1
st-line regimen (mo)2631ART use (%):TDF+3TCZDV+3TCABC+3TCTDF+ZDV+3TC7226
1
1
ART
resistance
(%)
80
83Slide171
Drug-related AE (%)
in ≥2%
pts
ABT
(N=93)NRTI (N=99)Diarrhoea
7.5
14.1
Gastroenteritis
0
3
Rash
1.1
2
Headache
2.2
0
Dizzy
2.2
0
Haematuria
0
2Drug-related lab abnormalities (%) in ≥2% of ptsHigh triglycerides32.329.3High total
cholesterol12.92.0Wu H. J Int AIDS Soc 2016;19(Suppl 7):21-2(abs.O336) – oral presentationSlide172
What is the efficacy and safety profile of albuvirtide
+
LPV/r
in ARV-experienced
adults with HIV-1?Once-weekly albuvirtide
+ daily LPV/r seems well
tolerated and non-inferior
to 2
nd
-line
regimen in patients
who failed 1
st
-line treatment