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practice HIV International Congress of Drug Therapy in HIV Infection Glasgow UK 2326 October 2016 About the slide deck Goal How to reach the goal Structure of slide deck ID: 738654

2016 hiv aids pts hiv 2016 pts aids int soc suppl abs oral ftc poster hcv study virological tdf drv 3tc dtg

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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These slides may not be published or posted online without permission from the publisher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