Debating view on less ART

Strategies under evaluation Andrea De Luca

Dipartimento Biotecnologie Mediche Università di Siena Department of Infectious Diseases, Siena University

Hospital, Italy

Conflicts of interest • Research grants from:

– ViiV Healthcare – Gilead (Fellowship Program) – Merck, Sharp and Dohme

• Paid consultancies: – ViiV Healthcare – Gilead Sciences – Merck, Sharp and Dohme – Janssen – Bristol-Myers Squibb

Outline

• Regimens with reduced number of drugs

• Use in clinical practice

• Evidence from studies

– First-line

– Switch in virosuppressed individuals

June 2017 Report

for 2017, first 6 months

0.8%

5.2%

6.4%

8.9%

1.7%

3.2%

4.2%

1.7%

0%

1%

2%

3%

4%

5%

6%

7%

8%

9%

10%

2006-2008 2009-2011 2012-2014 2015-2017

Proportion of mono/dual PI therapies according to calendar period of starting

Dual

Mono

June 2017 Report

Most used DRV-containing mono/dual therapies 295

226

137

63 49 33 32 29 54

0

50

100

150

200

250

300

350

DRV/r DRV/r,RAL 3TC,DRV/r ETV,DRV/r DRV/r,DGV DRV,cob DRV/r,MRV 3TC,DRV,cob other

165

114

47 34

59

0

50

100

150

200

3TC,ATV/r ATV/r ATV/r,RAL ATV,RAL other

Most used ATV-containing mono/dual therapies

June 2017 Report

DGV-containing mono/dual therapies according to calendar period

133

49 44

18 10

19

0

20

40

60

80

100

120

140

3TC,DGV DRV/r,DGV RPV,DGV DRV,DGV,cob ATV,DGV other

Proportion of patients with a VL<=80 copies/mL at 12 months from starting their first ART regimen by calendar year of initiation

June 2017 Report

17.0%

38.3% 43.6%

52.5% 58.1%

75.0% 78.1% 77.1%

80.5% 83.1%

85.5% 88.8% 90.5% 88.9% 88.1% 89.9% 91.2%

94.3% 95.4% 95.7%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

Reasons for stopping at least one drug of the first ART regimen within 1 year, according to calendar period of starting

N = therapy interruptions per period

June 2017 Report for 2017, first 6

months

13

.0%

4.4

%

6.2

%

8.7

%

9.2

%

7.3

%

9.7

%

3.7

%

7.8

% 1

6.7

%

16

.5%

18

.9%

21

.4%

21

.8%

25

.7%

22

.1%

20

.6%

11

.5%

11

.2%

5.2

%

6.8

%

0.5

0%

4.4

2%

15

.56

%

11

.93

%

7.9

1%

21

.22

%

25

.24

%

57

.1%

61

.2%

40

.9%

51

.4%

52

.7%

44

.9%

36

.4%

0%

10%

20%

30%

40%

50%

60%

70%

1997-1999 (N=602) 2000-2002 (N=294) 2003-2005 (N=257) 2006-2008 (N=218) 2009-2011 (N=455) 2012-2014 (N=735) 2015-2017 (N=206)

FAILURE OTHER PATIENT'S DECISION SIMPLIFICATION TOXICITY

Monotherapies? • PI/r monotherapies

– Inferior to triple, but very rare resistance selection – Reinduction + 2NA works – DRV/r more solid data: inferior with nadir CD4<200

• DTG monotherapy: catastrophe – Inferior AND resistance selection – How to throw away the most precious ARV class

Pt BL 3rd agent

(with F/TDF)

Timing

of Failure

HIV-RNA at

Failure (c/ml)

Integrase Sequence

at Failure

1 RPV W4 71,600 No RAMs

2 EFV W12 678 Not successful

3 RPV W30 3,510 No RAMs

4 RPV W30 1,570 S230R

5 DTG W36 1,440 Not successful

6 RPV W48 4,990 No RAMs

7 NVP W60 3,470 R263K

8 NVP W72 4,180 N155H

• Study prematurely discontinuation due to predefined stopping rule (emergent INSTI resistance)

DTG monotherapy efficacy was inferior by Week 48

DTG as Maintenance Monotherapy For HIV-1

Characteristics of Virologic Failures on DTG Monotherapy*

* All CD4 T-cell nadir ≥210 cellsmm3 and >95% adherence (according to clinician)

DOMONO is a multicenter randomised non-inferiority trial comparing

96 patients on DTG 50mg QD monotherapy vs cART

DOMONO

Wijting I, et al. CROI 2017. Seattle, WA. Poster #451LB

Viral Suppression at W48 On-Treatment Analysis

92% 98%

0

20

40

60

80

100

DTG Mono(N=96)

cART(N=152)

p=0.03

% H

IV-R

NA

<2

00

c/m

l

Outcomes in Patients Failing DTG Monotherapy after Switch

Blanco JL, et al. CROI 2017. Seattle, WA. Oral #42

International, multi-cohort, retrospective study characterizing resistance of subjects who switched to DTG monotherapy 50 mg QD (n=122)

Virologic Failures (%)

Monotherapy

(N=122)

Bi / Tri-therapy

(N=1,082)

9% (n=11) 6% (n=64)

• 11 subjects in monotherapy arm experienced virologic failures • 45% - first INSTI • 64% - ≥95% adherence • 72% - ≥3 years virologic

suppressed prior to switch

High rate of genotypic resistance selection after DTG monotherapy failure

Summary of available studies: InSTI resistance in 15 of 20

Monotherapy Bi / Tri-therapy

82%

0% 9/11

Resistance Selection (%)

• Median time from VF until genotypic resistance testing: 5 weeks (IQR: 3-14)

• DTG monotherapy VFs led to different mutation pathways (92Q,118R,148X and 155H)

REDOMO: Pathways of Resistance in Subjects Failing DTG Monotherapy

Why mono?

• Less toxic than dual?

– With 3TC/FTC no/minimal added toxicity

• Less resistance selection (with PI/r)

– More resistance selection to 3TC/FTC or other classes?

Dual therapies in naives Study regimen control n Efficacy outcome Benefits/Harms

Gardel LPV/r+3TC LPV/r+2NA 416 Non-inferior (but comparator suboptimal)

Less AE, no resistance

PADDLE DTG+3TC no 20 18/20 <50 cps at 48w 1 suicide, 1PDVF re-suppressed (no change)

ACTG A5353

DTG+3TC no 120 31% VL>100K. 90% VS. 3 PDVF (1 with M184V and R263R/K)

ANDES DRV/r+3TC DRV/r+TVD 145 24w: VL<400 in 95% vs 97% 24w VL>100K all <400

GEMINI DTG+3TC DTG+TVD 700 ONGOING

Modern DRV/r+MVC QD DRV/r+TVD 804 Inferior Bone

NEAT001 DRV/r+RAL DRV/r+TVD 805 Non-inferior, inferior with CD4<200 or VL>100K

Bone, eGFR/InSTI-R selection

ANDES: DRV/RTV + 3TC vs DRV/RTV + 3TC/TDF

for ART-Naive Pts Randomized, open-label phase IV study in Argentina

Baseline: 24% HIV-1 RNA > 100,000 copies/mL

Slide credit: clinicaloptions.com Sued O, et al. IAS 2017. Abstract MOAB0106LB.

HIV-1 RNA < 400 c/mL (ITT) at Wk 24, n/N (%) DRV/RTV + 3TC DRV/RTV + 3TC/TDF

Overall 71/75 (95) 68/70 (97)

BL HIV-1 RNA > 100,000 copies/mL 20/20 (100) 15/15 (100)

1 virologic failure with DRV/RTV + 3TC/TDF

Interim Analysis

Wk 24

DRV/RTV + 3TC QD

(n = 75)

DRV/RTV + 3TC/TDF QD

(n = 70)

ART-naive pts with

HIV-1 RNA > 1000 copies/mL

(N = 145)

Primary Endpoint

Wk 48

Dosing: DRV/RTV, 800/100 mg; 3TC, 300 mg;

3TC/TDF, 300/300 mg.

ACTG A5353: HIV-1 RNA Levels and DTG

Concentration in Pts Experiencing PDVF

Slide credit: clinicaloptions.com Taiwo BO, et al. IAS 2017. Abstract MOAB0107LB. Reproduced with permission.

Pt 1

BL HIV-1 RNA > 100,000 copies/mL

Pt 2

BL HIV-1 RNA ≤ 100,000 copies/mL

Pt 3

BL HIV-1 RNA ≤ 100,000 copies/mL

HIV-1 RNA < limit of detection

No detectable DTG

HIV

-1 R

NA

(co

pie

s/m

L)

0

100

1000

10,000

100,000

1,000,000

Study Wk

0

1000

2000

3000

4000

50

0 2 4 8 12 16 20 24 32

None

0

100

1000

10,000

100,000

1,000,000

Study Wk

0

1000

2000

3000

4000

50

0 2 4 8 12 16 20 24 32

DT

G C

on

cen

tratio

n

(ng

/mL

)

0

100

1000

10,000

100,000

1,000,000

Study Wk

0

1000

2000

3000

4000

50

0 2 4 8 12 16 20 24 32

Off DTG

None M184V M184V

R263RK

Off DTG

V1061

HIV-1 RNA (copies/mL)

DTG concentration (ng/mL)

Dual RCT in treatment naive: unsuccessful studies

• DRV/r + MVC inferior to 2NA + DRV/r

– Well powered

• ATV/r + MVC inferior to 2NA + ATV/r

– Small, limited power

• ATV/r + RAL inferior to ATV/r + 2NA

– More jaundice, InSTI resistance selection

Maintenance dual ART: completed prospective trials Study Previous

regimen Study regimen control n Main Efficacy

outcome Benefits/Harms

ATLAS-M ATV/r+2NA ATV/r+3TC ATV/r+2NA 266 Non-inferior (superior)

eGFR, bone, AE/lipids

SALT Any triple ATV/r+3TC ATV/r+2NA 273 Non-inferior Less AE/lipids

OLE LPV/r+2NA LPV/r+3TC LPV/r+2NA 250 Non-inferior No/lipids

DUAL DRV/r+2NA DRV/r+3TC DRV/r+2NA 257 Non-inferior

MOBIDIP bPI+2NA bPI+3TC bPI 265 Dual>mono (VF 48w 3% vs 24.8%)

All had previous M184V

PROBE

PI/r+2NA DRV/r+RPV continue 60 Non-Inferior Bone, immune activation/lipids

Multineka LPV/r+2NA LPV/r+NVP LPV/r+2NA 67 Non-inferior

GUSTA Any triple DRV/r+MVC qd cont 133 Inferior AE, Bone, AP

MARCH PI/r+2NA PI/r+MVC bid 2NRTI+MVC bid

cont 395 PI/r+MVC inferior

Maintenance dual ART: completed prospective trials Study Previous

regimen Study regimen control n Main Efficacy

outcome Benefits/Harms

LATTE CAB+2NA CAB+RPV IM EFV+2NA 243 Non-inferior

LATTE-2 CAB (oral)+ABC/3TC

CAB+RPV IM q4W or q8W

CAB (oral)+ABC/3TC

309 Non-inferior Patients satisfaction/ISR

SWORD Any triple DTG+RPV continue 1024 Non-inferior Improved BMD and bone turnover markers

SPARE LPV+TVD DRV/r+RAL LPV+TVD 58 eGFR urinary b2M improved

Harness Any triple ATV/r+RAL ATV/r+2NA 109 Inferior

KITE 2NA+X LPV/r+RAL continue 60 Non-inferior no/lipids

ANRS 167 LAMIDOL

2NA+X DTG+3TC no 104 97% success w48 (1 PDVF)

Some excluded after induction (VF, tox)

DOLULAM Triple (81% bPI, 26% RAL)

DTG+3TC no 27 2 years: no VF 63% had historical RNA or DNA with M184I/V

ATV/r+3TC: ATLAS-M 96 weeks

Efficacy endpoint analyses at 96 weeks

12%

(95% CI 1.2; 22.8)

12.8%

(95% CI 1.9; 23.7)

13.5%

(95% CI 2.7; 24.3) 14.3%

(95% CI 3.4; 25.2)

Causes of treatment failure

ATV/rit+3TC

N=133

ATV/rit+2 NRTIs

N=133 p

Any cause 30 (22.6) 46 (34.6) 0.030

Virological Failure 2 (1.5)* 9 (6.8) 0.060

Adverse events

(potentially treatment-related)i 7 (5.3) 11 (8.3) 0.329

Adverse events

(not treatment related)ii 3 (2.3) 5 (3.8) 0.722

Withdrawal of consent 6 (4.5) 9 (6.8) 0.425

Loss to follow up 10 (7.5) 7 (5.3) 0.452

Other 2 (1.5) 5 (3.8) 0.447

Notes:

i. DT: skin rash (w4), renal colic (w26 and w49), biliary colic (w60), pancreatitis (w62), hypertriglyceridemia (w72), creatinine increase (w75); TT: creatinine increase (w3 and w7), osteopenia (w16), renal colic (w24, w60, w63, w77, w80), drug nephropathy (w43), proteinuria (w84), hyperbilirubinemia (w84).

ii. DT: sudden death (w10 and w78, suspect cardiac events), thyroid carcinoma (w24); TT: spinal disc herniation (w3), pneumonia (w12), abdominal cancer (w48), creatinine increase (w60), lung cancer (w72).

Values are expressed as n (%) * One VF at baseline, before treatment simplification.

Virological failures ID Visit

HIV-RNA

(cp/mL)

CD4

(cells/µL) Comments

Dual therapy arm

40 BL 1.452 904 VF at BL, before treatment simplification. GRT: no resistance.

164 W12 64 606 VF with low VL (64 and 248 cp/mL); after re-intensification with TDF, subsequent VL

83 cp/mL then <40 cp/mL. GRT: no resistance.

Triple therapy arm

85 W24 16.667 435 No subsequent data, lost to follow-up.

247 W24 7.684 895 Treatment change to elvitegravir/cobicistat/ tenofovir/emtricitabine with virological

suppression. GRT PR: 58E.

137 W36 2.797 626 VL <50 cp/mL without treatment change. GRT: no resistance.

168 W36 1.854 597 VL <50 cp/mL without treatment change. GRT: no resistance.

23 W48 26.720 305 VL <50 cp/mL without treatment change. GRT: no resistance.

107 W48 99.999 349 Subsequently lost to follow up. GRT PR: no resistance.

174 W60 22.572 341 Subsequent follow up not available. GRT PR: no resistance, RT: 101Q, 138A, 179I

(intermediate R to ETR, RPV).

230 w84 55 1.137

VF with low VL (55 and 78 cp/mL); treatment change to

abacavir/lamivudine+dolutegravir with virological suppression. GRT PR: no resistance

RT:215S.

78 w96 109 674 No subsequent data, lost to follow-up.

Evolution of renal function

Bone outcomes at 96 weeks

0.69

2.53

1.77

-2.95

-1.48

0.57

Lumbar Spine Total Hip Femoral neck

Changes in BMD at 96W (%) Dual arm TT arm

p= 0.02

p= ns p= ns

-15.62

-50.91

-23.3

14.7

-2.64

-45.2

-14.1

31.83

PTH Vitamin D Osteocalcin FAO

Bone turnover biomarkers (%)

Dual arm TT arm

p= ns p= ns

p= ns

p= ns

n=73

DT arm: 41

TT arm: 32

DUAL-GESIDA 8014: Dual DRV/RTV + 3TC

vs Triple DRV/RTV + FTC/TDF or ABC/3TC Randomized, multicenter, open-label, phase IV noninferiority

trial

– Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48 (ITT-e, FDA snapshot analysis)

Pulido F, et al. HIV Glasgow 2016. Abstract O331.

Pts with HIV-1 RNA

< 50 copies/mL for

> 6 mos; on triple

therapy* ≥ 2 mos;

HBsAg negative

(N = 257)

Switch to DRV/RTV + 3TC QD

(n = 129)

Continue Previous Triple Therapy*

(n = 128)

Wk 48 Primary endpoint

*Previous triple therapy regimens: DRV/RTV + FTC/TDF or DRV/RTV + ABC/3TC.

Stratified by baseline NRTI

28

Sensitivity analysis

DUAL-GESIDA 8014-RIS EST-45 study: 48 weeks results Observed data: excluding non-virological reasons for failure.

89% 87% 89% 97% 93% 89% 93%

98%

0%

20%

40%

60%

80%

100%

ITT-e (snapshot) ITT (snapshot) Per-Protocol (snapshot) Observed data

Pro

po

rtio

n o

fpat

ien

ts w

ith

H

IV v

iral

load

<5

0 c

op

ies/

mL

(%)

DUAL TRIPLE

3.4 5.7

3.9 2.4

-11 -10.2 -10.7

-5.8 -3.8

-2.2 -3.4 -1.7

-12

0

12

Dif

fere

nce

(%

) IC

95

%

29

Resistance testing (attempted in all rebounds with viral loads > 400 HIV-RNA copies/mL)

GROUP Week HIV-RNA ≥ 50 c/mL week 48 (SNAPSHOT)

1st viral load 2nd viral

load Genotype Mutations

DUAL Baseline Yes 80 800 Yes None

DUAL 24 Yes 988 259 Failed

DUAL 32 No 6,805 165 Yes None

TRIPLE 24 No 427 <20 Failed

TRIPLE 24 No 447,557 5,621 Yes V10I, W71T, D76W

DUAL-GESIDA 8014-RIS EST-45 study: 48 weeks results

DTG + 3TC as Maintenance Therapy

ANRS 167 LAMIDOL

Outcomes

• INDUCTION:

• 95% (104/110) eligible for dual therapy†

• MAINTENANCE:

• 97% (101/104) remained suppressed

• 1 virologic failure: W4 with VL 84 c/mL

• 1 therapeutic failure: W40 with blip VL 59 c/mL

• 1 lost to follow-up: W32

Switching to DTG+3TC maintained virologic suppression

in patients without history of virologic failure

INDUCTION DTG + 2 NRTIs (n=110)

MAINTENANCE DTG + 3TC (n=104)

Baseline Week 8 Week 48 & 56

* Subjects were on current ART for a median of 4 years (range: 0.5 - 11.3) † 6 subjects were ineligible for Phase 2: 3 with detectable VL and 3 with AEs (1 serious AE of suicide ideation)†

Inclusion Criteria • Current: 2 NRTIs + either NNRTI,

PI, or INSTI

• Maximum of 2 previous ART

modifications (simplification or one tolerability switch)

• Suppressed <50 c/ml for ≥2 years with no blips in previous 6 months*

• Wild type virus • CD4 nadir >200 cells/mm3

• >18 years • Normal labs & HBsAg negative

Joly V, et al. CROI 2017. Seattle, WA. Poster #458

3TC+PI/r dual therapies as maintenance strategies: resistance at failure 4 randomized controlled studies:

2 ATV/r+3TC (ATLAS, SALT), 96W

1 LPV/r+3TC (OLE)

1 DRV/r+3TC (DUET)

NO EMERGING RESISTANCE MUTATIONS AT FAILURE (1 case of M184V in the 3-drug arm of SALT)

In observational studies: 1 case of resistance to ATV (V32I-M46L-I50L-V82A) (no M184V)

Role of previous M184V in 3TC + PI/r or DTG?

31

Patients baseline characteristics in DT group (n=454)

M184V- (n=365) M184V+ (n=89) p

Age, years* 47 (40;54) 52 (48;57) <0.001

Male gender 265 (73%) 52 (58%) 0.008

Caucasian 322 (88%) 86 (97%) 0.081

Risk factor

sexual

IDU

other

232 (64%)

44(12%)

89 (24%)

58 (65%)

21 (24%)

10 (11%)

0.002

HCV co-infection 68 (19%) 24 (27%) 0.570

HBsAg+ 14 (4%) 2 (2%) 0.279

Previous AIDS events 41 (11%) 16 (18%) 0.085

Years from HIV diagnosis* 8 (4;14) 19 (16;23) <0.001

Years from first cART initiation* 6 (3;11) 17 (13;19) <0.001

CD4 nadir, cells/µL* 224 (81;310) 131 (52;199) <0.001

CD4, cells/µL* 627 (462;786) 616 (409;899) 0.310

Previous major PI resistance mutations 12 (3%) 29 (33%) <0.001

Type of DT:

3TC+PI/r

3TC+INI

254 (70%)

111 (30%)

67 (75%)

22 (25%)

0.290

Calendar year of BL 2014 (2013;2015) 2014 (2012; 2015) 0.174 Values are expressed as n (%) except for * median (IQR)

10%

24%

37%

28%

1% Dual therapies

3TC+LPV/r

3TC+ATV/r

3TC+DRV/r

3TC+DTG

3TC+RAL

Gagliardini R 15th European MHH, 2017

Virological outcomes on dual therapies

• Overall incidence of VF: 2.35 per 100 PYFU

– 13 over 572 PYFU in M184V- pts (2.27 per 100 PYFU)

– 4 over 153 PYFU in M184V+ pts (2.63 per 100 PYFU)

• Median follow-up: 1.2 years (IQR 0.6-2.4)

M184V- 92.5% (95% CI 87.2; 97.8) M184V+ 92.5% (95% CI 85.0; 99.9)

p=0.824

Estimated probability of remaining free from VF with dual therapy at 3 years

3 DRV/r+3TC, 1 ATV/r+3TC

Figure 3: estimated probability of remaining free from VF with dual therapy versus monotherapy

• Virological blips occurred in 29/352 (8%) M184V- pts and 15/84 (18%) M184V+ (p=0.009).

Gagliardini R 15th European MHH, 2017

Virological outcomes on dual therapies vs monotherapies

Overall dual therapy versus monotherapy

Estimated probability of remaining free of VF at 3 years DT 92.5% (95% CI 87.9; 97.0)

Mono 81.5% (95% CI 73.1; 89.9) p<0.001

Dual therapy M184V+ versus monotherapy

Estimated probability of remaining free of VF at 3 years

DT M184V+ 92.5% (95% CI 85.0; 99.9) Mono 81.5% (95% CI 73.1; 89.9)

p=0.049

Gagliardini R 15th European MHH, 2017

Snapshot Outcomes at Week 48 (Pooled)

Virologic outcomes Adjusted treatment

difference (95% CI)*

0

20

40

60

80

100

Virologicsuccess

Virologicnon-response

No virologicdataH

IV-1

RN

A <

50

c/m

L, %

DTG + RPV (n=513)CAR (n=511)

95 95

<1 1 5 4

CAR DTG + RPV

-8 -6 -4 -2 0 2 4 6 8

-3.0 2.5

-0.2

*Adjusted for age and baseline 3rd agent.

SWORD 1 and 2: Switching to DTG+RPV vs Maintaining CAR

Percentage-point difference

Llibre JM, et al. CROI 2017. Seattle, WA. Oral #44LB

Randomized, open-label, multicenter phase III trials demonstrated that switch to DTG + RPV noninferior to remaining on baseline ART at Wk 48 in virologically suppressed pts [1]

Current analysis assessed BMD in pts who continued on TDF-containing triple ART regimen or switched from TDF-containing triple ART to DTG + RPV (N = 102)[2]

SWORD 1 & 2 Substudy: BMD Impact of Switch

From TDF-Based ART to DTG + RPV

Slide credit: clinicaloptions.com

1. Llibre JM, et al. CROI 2017. Abstract 44LB. 2. McComsey G, et al. IAS 2017. Abstract

TUPDB0205LB. Reproduced with permission.

Change From BL in BMD at Wk 48

Total Hip* Lumbar Spine

Me

an

Ad

juste

d C

han

ge

in

BM

D F

rom

BL

(%

) 2.5

1.5

0.5

-0.5

-1.5

-2.5 BL 48 Wks

P = .014

1.34

0.05

DTG + RPV (n = 46)

Continued TDF-based

ART (n = 35)

BL 48 Wks

P = .039 1.46

0.15

*Primary endpoint.

Cabotegravir: INSTI formulated as PO tablet and for long-acting IM injection

LATTE-2: phase IIb study in which pts randomized to CAB 400 mg IM + RPV 600 mg Q4W, CAB 600 mg IM + RPV 900 mg Q8W, or CAB 30 mg PO + ABC/3TC 600/300 mg QD after induction/ virologic suppression with oral CAB + ABC/3TC (N = 309)[1,2]

LATTE-2: 96-Wk Results for Cabotegravir IM +

Rilpivirine IM as Long-Acting Maintenance ART

Slide credit: clinicaloptions.com References in slidenotes.

At 96 wks, ~ 30% of pts receiving IM injection experienced ISR

– 99% of ISRs mild/moderate

Withdrawals between Wks 48 and 96: CAB IM arms, n = 4 (n = 1 for AE, n = 3 withdrew consent); CAB PO arm, n = 3 (all withdrew consent)

No additional PDVFs after Wk 48 in any arm

~ 88% of pts receiving CAB IM very satisfied to continue present treatment at Wk 96 vs 43% receiving CAB PO

Phase III maintenance trials (ATLAS and FLAIR) moving forward with Q4W dose[3,4]

Virologic

Success*

94 87 84

4 0 2 2

13 14

Virologic

Nonresponse

No

Virologic

Data

Pts

(%

)

100

80

60

40

20

0

CAB IM + RPV Q4W (n = 115)

CAB IM + RPV Q8W (n = 115)

CAB PO + ABC/3TC (n = 56)

Wk 96 Virologic Efficacy

Treatment Difference vs CAB PO (95% CI)

CAB IM Q4W: 3.0% (-8.4% to 14.4%)

CAB IM Q8W: 10.0% (-0.6% to 20.5%)

*HIV-1 RNA < 50 copies/mL.

Dual therapies: considerations • Most solid evidence of efficacy in maintenance therapy

– PI/r+3TC (..and M184V does not preclude its activity): no resistance selection – DTG+RPV

• Caveat: PI/r tolerability? • Toxicity benefits of dual vs triple:

– Bone and renal, due to TDF discontinuation – Will TAF avoid the need of dual?

• Reduced costs – Not for all dual therapies

• DTG + 3TC future game changer? – Naive, maintenance – Beyond efficacy, tolerability and costs will still count – Previous M184V? Resistance selection?