OÙ EN SOMMES NOUS EN 2018?

Dr Roger Philip LeBlanc BSc MDCM FRCPC Clinique OPUS: médecine urbaine

Président et Fondateur Directeur Division médicale ITSS | VIH/SIDA | Recherche

GMF Satellite du DMRG Centre sud Montreal Services des Maladies Virales Chronique CUSM

Professeur Adjoint de l’Université du McGill

LA TRITHÉRAPIE:

QU’EN PENSENT LES EXPERTS?

OÙ EN SOMMES NOUS EN 2018?

Conflits d’interêt potentiels Consultant ponctuel; chercheur ou conférencier

lors d’activités soutenues par les sociétés suivantes : ViiV HealthCare, Merck, Gilead

PLAN: TRITHÉRAPIE EN 2018 1: ÉTUDES NAÏFS GS 1489;GS 1490; DRIVE-AHEAD; AMBER; NAMSAL

2: TRAITEMENT EXPERIMENTÉS: SWITCH GS 1844 GS 1878

DRIVESHIFT; EMERALD

3: COÛTS RELATIFS

4: QUAND? QUI? COMMENT?

5: CONCLUSION

RECREATIONAL

NON-RECREATIONAL

DRUG USE / ABUSE

LOSS OF JOB

SECURITY

LOSS OF BENEFITS

Les études de trithérapie chez les naïfs

Study Design Studies 1489 & 1490: B/F/TAF vs DTG-containing Regimens in Treatment-Naïve Adults

8

Study 14891

HIV-1 RNA ≥500 c/mL

eGFRCG ≥50 mL/min

HLA B*5701 negative

HBV negative

Genotypic sensitivity to FTC, TFV, ABC, 3TC

B/F/TAF qd

DTG/ABC/3TC qd

DTG/ABC/3TC placebo qd

B/F/TAF QD

48 Week 0

1:1

n=314

n=315

Study 14902 HIV-1 RNA ≥500 c/mL

eGFRCG ≥30 mL/min

Genotypic sensitivity to FTC, TFV

B/F/TAF qd

DTG + F/TAF qd

DTG + F/TAF placebo qd

B/F/TAF placebo qd

1:1

n=320

n=325

Primary Endpoint

ABC, abacavir; eGFRCG, estimated glomerular filtration rate by Cockcroft Gault; FTC, emtricitabine; HBV, hepatitis B virus;

HLA, human leukocyte antigen; TFV, tenofovir; 3TC, lamivudine.

1. Gallant J, et al. Lancet 2017;390:2063-72; 2. Sax P, et al. Lancet 2017;390:2073-82.

96 144

Results: Pooled Baseline Characteristics

9

B/F/TAF

n=634

DTG/ABC/3TC

n=315

DTG + FTC/TAF

n=325

Median age, y (range) 32 (18–71) 32 (18–68) 34 (18–77)

Male, % 89 90 89

Race/ethnicity, %

Black or African descent 33 36 31

Hispanic/Latino 25 21 25

Median HIV-1 RNA, log10 copies/mL (Q1, Q3) 4.42 (4.00, 4.88) 4.51 (4.04, 4.87) 4.45 (4.03, 4.84)

HIV-1 RNA >100,000 copies/mL, % 19 16 17

Median CD4 cell count, cells/µL (Q1, Q3) 442 (293, 590) 450 (324, 608) 441 (297, 597)

CD4 count <200 cells/µL, % 13 10 10

HBV coinfection, %* 1 Excluded 2

HCV coinfection, %† 1 1 2

Median eGFRCG, mL/min (Q1, Q3) 122 (104, 143) 123 (107, 144) 121 (103, 145) *Positive HBV surface antigen and/or isolated positive HBV core antigen with HBV DNA ≥20 IU/mL; †Positive hepatitis C

virus (HCV) antibody and HCV RNA ≥15 IU/mL. Q, quartile.

Virologic Response by Visit (FAS) HIV-1 RNA <50 copies/mL, Missing=Excluded Analysis

All arms showed rapid suppression of viremia, with the majority of participants

<50 copies/mL by Week 412-13

10

a

Part

icip

ants

, %

0,

20,

40,

60,

80,

100,

0 12 24 36 48

76.3 90.7 96.3 97.9 98.8 99.1

75.9 91.6 96.1 98.4 98.3 97.7

79.6 89.9 95.3 97.5 98.1 99.3

B/F/TAF

DTG/ABC/3TC

DTG + F/TAF

4 8

Weeks

Virologic Efficacy: HIV-1 RNA <50 copies/mL, Missing=Excluded Analysis Baseline HIV-1 RNA >100,000 copies/mL

Virologic response rates by visit were also rapid and similar between treatment arms in

participants with high baseline VL

11

a

Part

icip

ants

, %

0,

20,

40,

60,

80,

100,

0 12 24 36 48

25.0 69.8 84.2 92.7 96.3 99

30.0 65.3 83.3 95.7 97.9 97.9

24.1 58.5 79.6 88.7 94.3 96.2

B/F/TAF

DTG/ABC/3TC

DTG + F/TAF

4 8

Weeks

Treatment Naïve: Study 1489 Virologically Suppressed: Study 1844

Week Longitudinal Model

Week Longitudinal Model 4 12 48 4 12 48

HIV-SI Bothersome Symptom*

Fatigue/loss of energy

Dizzy/lightheadedness

Nausea/vomiting

Loss of appetite

Sad/down/depressed

Nervous/anxious

Difficulty sleeping

PSQI

Poor sleep quality

Significant Differences in Bothersome Symptoms and PSQI

13

*Only symptoms where ≥2 time points/models showed significance in either study are presented;

No differences between arms

Favors DTG/ABC/3TC

Favors B/F/TAF

= statistically significant (p <0.05) based on adjusted logistic

regression or longitudinal model favoring the B/F/TAF group

D/c for AEs: 1.9% with BIC/FTC/TAF vs 1.6% with DTG + FTC/TAF

Fewer TRAEs with BIC/FTC/TAF vs DTG + FTC/TAF (P = .02)

Grade 3/4 laboratory abnormalities similar between arms

No tubulopathy or d/c for renal AEs in either arm

No difference in lipid changes between arms

GS-1490: Safety Outcomes Through Wk 96

Stellbrink. Glasgow 2018. Abstr O211. Slide credit: clinicaloptions.com

All-Grade AEs, % BIC/FTC/TAF

(n = 320)

DTG + FTC/TAF (n = 325)

P Value

Any AE 88 89 --

Any TRAE 20 28 .02

TRAEs occurring with ≥ 3% frequency

• Nausea 3 5 --

• Diarrhea 3 3 --

• Headache 4 3 --

ZÉRO

DIFFERENCE

http://www.clinicaloptions.com/


Multicenter, randomized, double-blind phase III noninferiority trial[1]

Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48 (noninferiority margin: -10%)[2]

‒ DOR/3TC/TDF vs EFV/FTC/TDF: 84.3% vs 80.8% (difference: 3.5%; 95% CI: -2.0% to 9.0%)

‒ Neuropsychiatric events less frequent with DOR/3TC/TDF

DRIVE-AHEAD: DOR/3TC/TDF vs EFV/FTC/TDF in Treatment-Naive Adults at Wk 96

Slide credit: clinicaloptions.com

Treatment-naive adults with HIV-1 RNA ≥ 1000 copies/mL

and no resistance to study drugs (N = 728)

Current Analysis Wk 96

Primary Analysis Wk 48

Stratified by HIV-1 RNA (> vs ≤ 100,000 copies/mL), chronic HBV or HCV coinfection status

DOR/3TC/TDF 100/300/300 mg QD + EFV/FTC/TDF Placebo

(n = 364)

EFV/FTC/TDF 600/200/300 mg QD + DOR/3TC/TDF Placebo

(n = 364)

Open-label extension for 96 wks

1. Orkin. IDWeek 2018. Abstr LB1. 2. Orkin. Clin Infect Dis. 2018;[Epub].



DRIVE-AHEAD: Virologic Outcomes at Wk 96

Orkin. IDWeek 2018. Abstr LB1. Reproduced with permission. Slide credit: clinicaloptions.com

HIV-1 RNA < 50 copies/mL by Observed Failure Analysis, % (n*)

DOR/3TC/TDF

EFV/FTC/TDF

All participants 83.7 (337) 85.9 (312)

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

86.9 (268) 71.0 (69)

87.5 (248) 79.7 (64)

BL CD4+ cell count, cells/mm3

≤ 200 > 200

65.0 (40)

86.2 (297)

82.1 (39)

86.4 (273)

FDA Snapshot Analysis

Treatment difference: 3.8% (95% CI: -2.4% to 10.0%)

*n refers to total number of participants per subgroup.

100

80

60

40

20

0

77.5 73.6

HIV

-1 R

NA

< 5

0 c

op

ies/

mL

(%)

DOR/3TC/TDF EFV/FTC/TDF

Resistance:

‒ DOR-R in 6 patients (1.6%) in DOR arm vs EFV-R in 13 patients (3.8%) in EFV arm

‒ NRTI-R in 1.4% vs 1.6%, respectively

Small decreases in fasting LDL-C, non–HDL-C with DOR vs increases with EFV



DRIVE-AHEAD: Safety Outcomes Through Wk 96

Less frequent drug-related AEs, AE-related d/c with DOR/3TC/TDF vs EFV/FTC/TDF

Less frequent neuropsychiatric AEs with DOR/3TC/TDF vs EFV/FTC/TDF

Orkin. IDWeek 2018. Abstr LB1. Reproduced with permission. Slide credit: clinicaloptions.com

AE, n (%) DOR/3TC/TDF (n = 364)

EFV/FTC/TDF (n = 364)

Any AE Drug related

321 (88) 116 (32)

339 (93) 236 (65)

Serious AE Drug related

21 (6) 1 (< 1)

30 (8) 4 (1)

AE leading to d/c Drug related Serious Serious drug

related

11 (3) 8 (2) 2 (1)

1 (< 1)

27 (7) 24 (7) 4 (1)

3 (1)

Death 0 2 (1)

Predefined Neuropsychiatric AEs, %

DOR/3TC/TDF (n = 364)

EFV/FTC/TDF (n = 364)

Dizziness 10.2 38.2

Sleep disorders and disturbances

14.0 27.5

Altered sensorium 4.9 8.5

Depression and suicide/self-injury

5.2 7.4

Psychosis and psychotic disorders

0.5 1.4



AMBER: DRV/COBI/FTC/TAF vs DRV/COBI + FTC/TDF in Treatment-Naive Adults at Wk 96

Multicenter, randomized, double-blind, noninferiority phase III trial[1]

Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48 (FDA Snapshot)(noninferiority margin: -10%)[2]

‒ DRV/COBI/FTC/TAF vs DRV/COBI + FTC/TDF: 91.4% vs 88.4% (difference: 2.7%; 95% CI: -1.6% to 7.1%; P < .0001)

‒ Less impact on renal, bone markers with DRV/COBI/FTC/TAF vs DRV/COBI + FTC/TDF

1. Orkin. Glasgow 2018. Abstr O212. 2. Eron. AIDS. 2018;32:1431.

DRV/COBI/FTC/TAF (n = 362)

DRV/COBI + FTC/TDF (n = 363)

Switch to DRV/COBI/FTC/TAF (n = 295)


Treatment-naive adults with HIV-1 RNA ≥ 1000 copies/mL, CD4+ counts > 50 cells/mm3, genetic susceptibility to DRV,

FTC, TFV, no HBV/HCV infection (N = 725)

Current Analysis Wk 96

Primary Analysis Wk 48

Rollover phase DRV/COBI/FTC/TAF

Database unblinded at Wk 48.




AMBER: Efficacy at Wks 48 and 96 (FDA Snapshot, ITT)


4% 3%

4% 8%


Wk 48

6% 4%

9% 12%

DRV/COBI + FTC/TDF (n = 363)

Wk 48 Wk 96 Wk 96

HIV-1 RNA ≥ 50 c/mL

No virologic data

HIV

-1 R

NA

< 5

0 c

op

ies/

mL

(%)

91 88 85 84

Virologic response at Wk 96 consistent across subgroups

‒ BL VL >/≤ 100,000 copies/mL, BL CD4+ ≥/< 200 cells/mm3, age >/≤ 50 yrs, sex, race

Resistance analysis in 9/15 patients with PDVF with DRV/COBI/FTC/TAF vs 8/19 in control arm through Wk 96

‒ 1 patient with M184V/I in each arm

‒ No evidence of emergent DRV, primary PI, or TFV RAMs

FDA Snapshot Analysis at Wks 48 and 96

0

20

40

60

80

100

Orkin. Glasgow 2018. Abstr O212. Reproduced with permission.



AMBER: Safety at Wks 48 and 96

No d/c for bone, renal, CNS AEs in DRV/COBI/FTC/TAF arm

No Fanconi syndrome or tubulopathy

No clinically relevant effect on eGFR in either arm

Less effects on bone, renal markers with DRV/COBI/FTC/TAF

Similar lipid changes across arms

Orkin. Glasgow 2018. Abstr O212. Reproduced with permission. Slide credit: clinicaloptions.com

AEs in DRV/COBI/FTC/TAF Arm, n (%)

BL to Wk 48 (n = 362)

BL to Wk 96 (n = 362)

Patient-yrs of exposure 323 626

≥ 1 AE, any grade 312 (86) 334 (92)

Study drug-related AEs 128 (35) 142 (39)

Study drug-related AEs in ≥ 5% patients

Diarrhea 33 (9) 34 (9)

Rash 22 (6) 22 (6)

Nausea 20 (6) 20 (6)

Study drug-related grade 3/4 AEs

6 (2) 11 (3)

≥ 1 serious AE 17 (5) 39 (11)

Study drug-related serious AEs

0 1 (< 1)

≥ 1 AE leading to d/c 8 (2) 10 (3)



NAMSAL: DTG- vs EFV 400 mg–Based ART in Treatment-Naive Patients in Cameroon

Multicenter, randomized, open-label phase III noninferiority trial

Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48 (FDA Snapshot)

‒ Noninferiority tested with 10% margin

Cournil. Glasgow 2018. Abstr O342. Slide credit: clinicaloptions.com

ART-naive adults with HIV-1 RNA ≥ 1000 copies/mL

(N = 613)

Wk 48 Primary Endpoint

DTG 50 mg QD + 3TC/TDF (n = 310)

EFV 400 mg QD + 3TC/TDF (n = 303)

Follow-up through 96 wks

Stratified by HIV-1 RNA at screening, site



NAMSAL: Efficacy at Wk 48 (FDA Snapshot)

AEs: DTG 11% vs EFV 400 8%; AIDS-defining events: DTG 8% vs EFV 400 10%

Virologic failure (HIV-1 RNA > 1000 c/mL) observed in 19 pts; emergent resistance in 0/3 DTG failures vs 9/16 EFV 400 failures

Cournil. Glasgow 2018. Abstr O342. Slide credit: clinicaloptions.com

Outcome at Wk 48 DTG + 3TC/TDF

(n = 310) EFV 400 + 3TC/TDF

(n = 303) Treatment Difference DTG - EFV (95% CI), %

HIV-1 RNA < 50 c/mL (virologic success), n (%) 231 (74.5) 209 (69.0) 5.5 (-1.6 to 12.7)

HIV-1 RNA < 200 c/mL/< 1000 c/mL, % 89.0/91.9 83.5/86.5 --

HIV-1 RNA > 50 c/mL (virologic failure), n 62 70 --

D/c for death 6 7 --

D/c other reasons (LTFU, withdrawn) 9 15 --

HIV-1 RNA < 50 c/mL by BL VL, n/N (%)

HIV-1 RNA < 100,000 c/mL 94/103 (91.3) 86/103 (83.5) 7.8 (-1.2 to 16.8)

HIV-1 RNA > 100,000 c/mL 137/207 (66.2) 123/200 (61.5) 4.7 (-4.6 to 14.0)

HIV-1 RNA > 500,000 c/mL 51/93 (54.8) 55/95 (57.9) --



TRITHÉRAPIE: SWITCH

‡

Methods: Figure 1. B/F/TAF Switch Study Designs

29

‡

Results: Figure 2. Virologic Outcome at Week 48 by FDA Snapshot

30

‡

Table 2. Distribution of Baseline HIV-1 Subtypes

31

Number of Participants, n (%)

HIV-1 Subtype B/F/TAFn=405

PI + 2NRTI

n=125

ABC/DTG/3TC

n=138

B 327 (81%) 79 (63%) 99 (72%)

Non-B 27 (7%) 15 (12%) 6 (4%)

A 2 (<1%) 0 0

A1 2 (<1%) 0 0

AE 3 (<1%) 0 3

AG 5 (1%) 5 (4%) 0

C 4 (1%) 6 (5%) 1 (<1%)

Complex 9 (2%) 3 (2%) 2 (1%)

D 1 (<1%) 0 0

F 1 (<1%) 0 0

H 0 1 (<1%) 0

Undetermined 51 (13%) 31 (25%) 33 (24%)

‡

Figure 4. Week 48 Virologic Outcome of B/F/TAF-treated Participants Stratified by Baseline Resistance Category

34

No significant differences in virologic outcome by presence or absence of baseline resistance in the B/F/TAF group were observed.

BL resistance

INTI~10-15%

NNRTI ~18%

IP/r ~5%

INSTI 0%

‡

Table 9. Resistance Development through Week 48

35

Resistance Category

Number of Participants, n (%)

B/F/TAF

n=572

PI + 2NRTI

n=287

ABC/DTG/3TC

n=281

Resistance Analysis Population (RAP) 5 (0.9%) 5 (1.7%) 2 (0.7%)

Data Available for Any Gene (% of RAP) 2 (40%) 5 (100%) 2 (100%)

PR/RT Data Available (% of RAP) 2 (100%) 5 (100%) 2 (100%)

IN Data Available (% of RAP) 1 (20%) 2 (40%) 2 (100%)

Resuppressed HIV-1 RNA <50 c/mL (% of RAP) 2 (40%) 2 (40%) 1 (50%)

Developed Resistance to Study Drugs 0 1 (0.3%) 0

NRTI-R Substitutions Acquired - L74V -

Change Baseline in eGFRCG Through Week 48

36

Study 380-1878: HIV Suppressed Adults Switched from boosted DRV or ATV + 2 NRTIs

p <0.001

–4.3 mL/min

0.2 mL/min

B/F/TAF SBR

Weeks

Media

n (

Q1, Q

3)

eG

FR

CG C

hange fro

m

BL, m

L/m

in

Daar E, ID Week, 2017, Abstract # 67504

‡

‡

Change in eGFR

CG Over Time

Study 380-1844

No discontinuations due to renal AEs and no cases of renal tubulopathy in either arm

*From 2-sided Wilcoxon rank-sum test. 37

‡ Changes in Spine and Hip BMD Through Week 48 Study 380-1844

*From ANOVA model for comparison of B/F/TAF vs DTG/ABC/3TC at Week 48. 38

Percent Change from Baseline in Quantitative Proteinuria at Week 48

39

Study 380-1878: HIV Suppressed Adults Switched from Boosted DRV or ATV + 2 NRTIs

Media

n P

erc

enta

ge C

hange

from

Baselin

e, %

β2M:Cr RBP:Cr UACR

SBR B/F/TAF

Baseline FTC/TDF-Containing Regimen Baseline ABC/3TC-Containing Regimen

-2,1

-17,7

-40,3

9,9

34,9 31,6

-50,

-25,

0,

25,

50,

4,2 5,4

-19,5

1,1

25,8

7,3

-50,

-40,

-30,

-20,

-10,

0,

10,

20,

30,

40,

β2M:Cr RBP:Cr UACR

Daar E, ID Week, 2017, Abstract # 67504

UACR: urine albumin to creatinine ratio; RBP: retinol binding protein to creatinine ratio; β2M:Cr: beta-2-microglobulin to creatinine ratio

‡


Primary endpoint: HIV-1 RNA < 50 copies/mL (FDA Snapshot)

‒ Noninferiority margin: lower bound of 95% CI > -8%

‒ Time point comparisons: Wk 48 in immediate switch arm vs Wk 24 in baseline ART arm (primary); Wk 24 in each arm (secondary)

DRIVE-SHIFT: Switch to DOR/3TC/TDF vs Continuation of Baseline ART in Virologically Suppressed Adults

DOR/3TC/TDF* (n = 447)

Baseline ART†

(n = 223) DOR/3TC/TDF*

(n = 209)

DOR/3TC/TDF* (n = 427)

Adults with HIV-1 RNA < 40 copies/mL, stable ART for ≥ 6 mos with no prior

virologic failure or resistance to study drugs,

and eGFR ≥ 50 mL/min (N = 670)

Wk 48

*DOR/3TC/TDF dosing: 100/300/300 mg QD. †2 NRTIs + RTV- or COBI-boosted PI (ATV, DRV, LPV), EVG/COBI, or NNRTI (EFV, NVP, RPV).

Wk 24

Slide credit: clinicaloptions.com Kumar. IDWeek 2018. Abstr LB2.



DRIVE-SHIFT: Efficacy of Switch to DOR/3TC/TDF at Wks 24 and 48 vs Continued BL ART at Wk 24 (FDA Snapshot)

Kumar. IDWeek 2018. Abstr LB2. Slide credit: clinicaloptions.com

No evidence of treatment-emergent resistance in patients receiving DOR/3TC/TDF

Efficacy Analysis by FDA Snapshot, %

Immediate Switch to DOR/3TC/TDF

(n = 447)

Continued BL ART (n = 223)

Difference Between Arms, % (95% CI)

Wk 24 DOR/3TC/TDF vs Wk 24 BL ART

HIV-1 RNA < 50 copies/mL 93.7 94.6 -0.9 (-4.7 to 3.0)

HIV-1 RNA ≥ 50 copies/mL 1.8 1.8 0 (-2.3 to 2.3)

No virologic data 4.5 3.6 --

Wk 48 DOR/3TC/TDF vs Wk 24 BL ART

HIV-1 RNA < 50 copies/mL 90.8 94.6 -3.8 (-7.9 to 0.3)

HIV-1 RNA ≥ 50 copies/mL 1.6 1.8 -0.2 (-2.5 to 2.1)

No virologic data 7.6 3.6 --



DRIVE-SHIFT: Safety Outcomes Through Wk 48

Switch to DOR/3TC/TDF associated with significantly greater decreases in LDL-C (-16.5 vs -1.9 mg/dL) and non–HDL-C (-24.7 vs -1.3 mg/dL) at Wk 24 vs continued BL ART in patients receiving PI/RTV-based ART at study entry (P < .0001 for both comparisons)

Kumar. IDWeek 2018. Abstr LB2. Slide credit: clinicaloptions.com

AEs, n (%) Immediate Switch to DOR/3TC/TDF

Wks 0-48 (n = 447)

Continued BL ART Wks 0-24 (n = 223)

Late Switch to DOR/3TC/TDF

Wks 24-48 (n = 209)

Any AE Drug related

308 (68.9) 87 (19.5)

117 (52.5) 5 (2.2)

126 (60.3) 29 (13.9)

Serious AEs Drug related

13 (2.9) 2 (0.4)

8 (3.6) 0

4 (1.9) 1 (0.5)

D/c due to AE Drug related

11 (2.5) 7 (1.6)

1 (0.4) 0

4 (1.9) 4 (1.9)

Death 0 0 0



EMERALD: Switch From Suppressive Boosted PI + FTC/TDF to DRV/COBI/FTC/TAF at Wk 96


Primary endpoint: cumulative virologic rebound at Wk 48 (ITT)

‒ Noninferiority margin: upper bound of 95% CI < 4%

‒ Switch to DRV/COBI/FTC/TAF vs continue boosted PI + FTC/TDF: 2.5% vs 2.1% (difference: 0.4%; 95% CI: -1.5% to 2.2%; noninferiority P < .0001)

Adults with HIV-1 RNA < 50 c/mL while receiving boosted PI* +

FTC/TDF; no prior VF on DRV; no DRV RAMs if historical genotype

known (N = 1141)

Rollover to DRV/COBI/FTC/TAF

Immediate Switch to DRV/COBI/FTC/TAF† (n = 763)

Continue Boosted PI + FTC/TDF (n = 378)

Slide credit: clinicaloptions.com Eron. IDWeek 2018. Abstr 1768. Orkin. Lancet HIV. 2018;5:e23.

Late Switch to DRV/COBI/FTC/TAF†

Wk 48 Primary Analysis

Wk 96 Current Analysis

*Eligible boosted PIs: ATV/COBI or RTV, DRV/COBI or RTV, LPV/RTV. †800/150/200/10 mg QD.

Stratified by boosted PI used at screening



EMERALD: Virologic Outcomes in DRV/COBI/FTC/TAF Immediate Switch Arm Through Wk 96 (ITT)

No RAMs to DRV, tenofovir, or FTC and no primary PI RAMs observed post baseline

Slide credit: clinicaloptions.com Eron. IDWeek 2018. Abstr 1768. Reproduced with permission.

FDA Snapshot at Wks 48 and 96

Pat

ien

ts, %

(9

5%

CI*

)

*2-sided exact Clopper-Pearson 95% CI.

Cumulative PDVR BL to Wk 48(n = 763)

BL to Wk 96(n = 763)

VL ≥ 50 c/mL, n (%) Rebounders

resuppressed, n/N

19 (2.5) 12/19

24 (3.1) 14/24

VL ≥ 200 c/mL, n (%) Rebounders

resuppressed, n/N

3 (0.4) 0/3

4 (0.5) 2/4

VL < 50 c/mL VL < 200 c/mL

DRV/COBI/FTC/TAF Wk 48 (n = 763)

DRV/COBI/FTC/TAF Wk 96 (n = 763)

100

80

60

40

20

0

95 91 91 95



EMERALD: Safety Outcomes in DRV/COBI/FTC/TAF Immediate Switch Arm Through Wk 96

Low rates of study drug–related grade 3/4 or serious AEs, AE-related d/c (all ≤ 2%) maintained from Wk 48 to Wk 96

No cases of subclinical proximal renal tubulopathy or Fanconi syndrome through Wk 96

Lipid parameters stable from Wks 48 to 96

Small (median change: ~ -1.0 mL/min) but statistically significant eGFR decrease from BL to Wk 96 (P < .05)

Slide credit: clinicaloptions.com Eron. IDWeek 2018. Abstr 1768.

BMD Outcome BL to Wk 48(n = 164)

BL to Wk 96(n = 173)

Mean percent change in hip BMD, % Proportion with

≥ 3% increase Proportion with

≥ 3% decrease

1.49

21

2

1.85*

29

3

Mean percent change in spine BMD, % Proportion with

≥ 3% increase Proportion with

≥ 3% decrease

1.45

31

8

2.00*

37

9

*P < .001 for within-arm change from BL by paired t-test.



NA-ACCORD Cohort: Weight Gain Following ART Initiation With INSTI- vs PI-/NNRTI-Based Regimens

Analysis of NA-ACCORD cohort of ART-naive adults who started 3-drug regimen with INSTI, PI, or NNRTI from January 2007 - December 2015 (N = 21,867)

Slide credit: clinicaloptions.com Lake. International Comorbidities WS 2018. Abstr ADRLH-71.

Baseline Characteristic NNRTI (n = 10,711)

PI (n = 7063) INSTI (n = 4093) Overall (N = 21,867)

Median age, yrs (IQR) 43 (32-52) 42 (32-50) 41 (30-51) 42 (32-51)

Black race/Hispanic ethnicity, % 40/8 41/9 38/9 40/8

Male sex, % 91 81 87 87

Median BMI (IQR) 25 (23-29) 25 (22-28) 25 (22-29) 25 (22-29)

Median calendar year started ART (IQR) 2010 (2008-2012) 2010 (2008-2011) 2013 (2011-2014) 2010 (2009-2012)

Median CD4+ cell count, cells/mm3 (IQR) 311 (178-451) 251 (107-405) 346 (171-516) 303 (154-451)

Median HIV-1 RNA, copies/mL (IQR) 40,480 (11,198-

120,016) 52,405 (12,830-

169,824) 42,657 (11,939-

144,709) 44,054 (11,796-

139,374)

ART agent, % RAL/EVG/DTG ATV/DRV/EFV

--/--/-- --/--/87

--/--/--

43/35/--

51/37/12

--/--/--

10/7/2

14/11/43



NA-ACCORD Cohort: Predicted and Observed Weight Change

Comparisons of predicted weight change

‒ RAL/DTG vs NNRTI: P < .05

‒ RAL/DTG vs PI: P = NS

‒ EVG vs PI: P = .03

‒ EVG vs NNRTI: P = NS

Comparisons of 2-yr weight change by INSTI

‒ RAL vs EVG: P = .03

‒ RAL vs DTG: P = .42

‒ EVG vs DTG: P = .07


Outcome INSTI

RAL DTG EVG

2-yr weight change, kg 5.4 5.6 3.4

Lake. International Comorbidities WS 2018. Abstr ADRLH-71.



Mise en garde: La majorité des nouvelles études ont exclus les co-infections VBH VHC; Peu avec des échecs de traitement antérieurs; Adhérence déjà établie; Peu avec plusieurs co-morbidités; Peu de données chez les femmes…la grossesse…la période de la conception. Les patients avec CD4 <200 et CV >100,000 ainsi que ceux avec CD4<50 et CV>500,000 demeurent une préoccupation.

Simplicité: QD INTI INNI IP (cobi ou rtv) INI en double et triple STR

Puissants |Pan-génotypes | Multi-ethniques | Pan-global | Personnes âgées

Diminution | Réversibilité | Stabilisation des «concerns» rénaux, osseux (TAF et sans TAF)

Diminution des «concerns» sur la mitotoxicité des INTI à long termes (TAF ABC FTC 3TC)

Diminution des symptômes SNC avec Doravirine et Bictégrevir

Habilité de surmonter des mutations transmises ou supprimées chez les naïfs et les

patients SWITCH (INTI INNI IP/r)

Favorable: Polypharmacie …Vieillissement…Co-morbidités…Lipides

La majorité des effets indésirables: peu fréquents, largement transitoires

La prise du poids avec les INI: effets secondaires ou reflet de leur innocuité?

EN CONCLUSION (1):

c

Pour nos patients très expérimentés procèder avec prudence…..surtout ceux avec des histoires de mono-; bi- ; “Add-On” et même trithérapies avec les IP 1ere génération…..HLA-B*5701 Status

Nous avons des années d’expérience avec une approche utilisant 3 médicaments en traitement d’initiation chez les naïfs et en traitant ceux avec des échecs antérieurs… Blips? Pénétration des sites sanctuaires? Adhérence moins que 85%…la durabilité? L’épidémie de l’obésité? Les ITTS? La drogue?

La bithérapie semble être une option rationnelle et raisonnable…$$$..mais HBV immunité doit être établie…..prudence avec ceux HBSAg- HBcAb+ HBSAb-

Les patients TND et TD persistent…importance envers des échecs futurs?

EN CONCLUSION (2)

Prix moyen sans assurance pour 30 jours

Evotaz (ATZ+ COBI) 865$

Delstrigo (Dor+3TC+TDF) 863$

Triumeq (ABC+3TC+DTG) 1216$

Descovy (TAF+FTC) 1075$

Juluca (Ril+DTG) 1175$

Odefsey (Ril+ TAF+ FTC) 1485$

Biktarvy (BIC+ TAF+FTC) 1420$

Genvoya (EVG+Cobi+ FTC+TAF) 1625$

Symtuza (DTG+Cobi+FTC+TAF) 1870$

DTG+3TC Pifeltro (Dor) ~500$

OÙ EN SOMMES NOUS EN 2018?

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