March 4-7, 2019; Seattle, Washington Higher patient-reported satisfaction with monthly injectable dual regimen compared with daily oral tablets. Released: March 11, 2019

1. FLAIR: Switch to Long-Acting CAB + RPV Following
Oral Induction in ART-Naive Patients Noninferior to
Continued DTG/ABC/3TC at Week 48
This program is supported by independent educational grants from
Gilead Sciences; Janssen Therapeutics; Merck & Co, Inc; and ViiV Healthcare.
CCO Independent Conference Coverage*
of the 2019 Conference on Retroviruses and Opportunistic Infections;
March 4-7, 2019; Seattle, Washington
*Clinical Care Options (CCO) is an independent medical education organization that provides conference
coverage and other unique educational programs for healthcare professionals.

2. FLAIR: Background
 LA ARVs may improve ART tolerability and facilitate adherence
 Potent dual ARV regimens may have a role in switch-maintenance strategies for
patients with virologic suppression on 3-drug ART
‒ DTG/RPV approved for use in this setting[1]
 LA CAB + RPV under investigation as maintenance therapy
‒ Phase II LATTE-2 found LA CAB IM + RPV IM maintained HIV-1 RNA < 50 copies/mL in
83% to 90% of patients after 160 wks and in 97% to 100% receiving optimized dosing[2]
 Current study designed to assess efficacy and safety of switching to LA CAB IM + LA
RPV IM after induction on DTG/ABC/3TC PO vs continuing DTG/ABC/3TC PO in ART-
naive patients[3]
1. DTG/RPV PI. 2. Margolis. Glasgow 2018. Abstr P118. 3. Orkin. CROI 2019. Abstr 140LB. Slide credit: clinicaloptions.com

3. FLAIR: Study Design
 Multicenter, randomized, open-label phase III noninferiority trial
Orkin. CROI 2019. Abstr 140LB. NCT02938520. Slide credit: clinicaloptions.com
LA CAB 400 mg IM +
LA RPV 600 mg IM Q4W
(n = 278)
Continue DTG/ABC/3TC PO QD‡
(n = 283)
ART-naive patients with
HIV-1 RNA ≥ 1000 copies/mL,
HBsAg negative,
no NNRTI RAMs*
(N = 629)
*K103N permitted. †Patients with HIV-1 RNA < 50 copies/mL from Wk 16 to Wk 20 continued to maintenance phase. ‡Alternative, non-ABC
NRTIs permitted for intolerance or HLA-B*5701 positivity. §Loading dose: LA CAB 600 mg IM + LA RPV 900 mg IM; regular dosing begun at Wk 8.
CAB 30 mg +
RPV 25 mg PO QD
(n = 283)
Current Analysis
Wk 48Wk 4§
DTG/ABC/3TC
PO QD‡
Induction Phase† Maintenance Phase
Wk 96Day 0
Wk 20
 Primary endpoint: HIV-1 RNA ≥ 50 copies/mL at Wk 48 by FDA Snapshot (6% noninferiority margin)
 Secondary endpoints: HIV-1 RNA < 50 copies/mL at Wk 48 by FDA Snapshot, resistance at confirmed
virologic failure, safety and tolerability, patient-reported outcomes

4. FLAIR: Baseline Characteristics in ITT-E Population
Orkin. CROI 2019. Abstr 140LB. Slide credit: clinicaloptions.com
Characteristic
LA CAB + LA RPV
(n = 283)
DTG/ABC/3TC
(n = 283)
Total
(N = 566)
Median age, yrs (range) 34 (19-68) 34 (18-68) 34 (18-68)
Age ≥ 50 yrs, n (%) 33 (12) 29 (10) 62 (11)
Female, n (%) 63 (22) 64 (23) 127 (22)
Race, n (%)
 White
 Black
 Other or missing
216 (76)
47 (17)
20 (7)
201 (71)
56 (20)
26 (9)
417 (74)
103 (18)
46 (8)
Median BMI (range) 24 (17-45) 24 (13-47) 24 (13-47)
HIV-1 RNA ≥ 100,000 copies/mL, n (%) 56 (20) 56 (20) 112 (20)
Median BL CD4+ cell count, cells/mm3 (IQR)
 < 200 cells/mm3, n (%)
437 (314-609)
16 (6)
452 (321-604)
23 (8)
444 (320-604)
39 (7)
Median Day 1 CD4+ cell count, cells/mm3 (IQR) 624 (473-839) 625 (472-799) 625 (473-818)
HIV/HCV coinfection, n (%) 19 (7) 9 (3) 28 (5)

5. Difference (%)
Difference (%)
FLAIR: Efficacy at Wk 48 in ITT-E Population
 Confirmed VF: n = 3 per arm; emergent NNRTI +
INSTI resistance in all CAB + RPV failures (all HIV-1
subtype A1), no resistance in DTG/ABC/3TC failures
Orkin. CROI 2019. Abstr 140LB. Reproduced with permission. Slide credit: clinicaloptions.com
Patients(%)
100
80
40
60
20
0
Virologic
Nonresponse
(≥ 50 c/mL)
Virologic
Success
(< 50 c/mL)
No
Virologic
Data
2.1 2.5
93.6 93.3
4.2 4.2
LA CAB + LA RPV
(n = 283)
DTG/ABC/3TC
(n = 283)
-10% NI
margin
Difference (%)
-3.7
0.4
-10 -8 -6 -4 -2 0 2 4 6 8 10
4.5
-2.8 2.1
-0.4
6% NI
margin
-10 -8 -6 -4 -2 0 2 4 6 8 10
Virologic Outcomes (FDA Snapshot) Adjusted Treatment Difference (95% CI)*
DTG/ABC/3TCLA CAB + LA RPV
DTG/ABC/3TC LA CAB + LA RPV
Key Secondary Endpoint
(HIV-1 RNA < 50 copies/mL)
LA CAB + LA RPV noninferior
to DTG/ABC/3TC
Primary Endpoint
(HIV-1 RNA ≥ 50 copies/mL)
LA CAB + LA RPV noninferior
to DTG/ABC/3TC
*Adjusted for sex, BL HIV-1
RNA (< vs ≥ 100,000 c/mL).

6. FLAIR: Plasma Trough Concentrations by Visit
 Plasma concentrations with IM CAB and RPV similar to effective PO regimens
Orkin. CROI 2019. Abstr 140LB. Reproduced with permission. Slide credit: clinicaloptions.com
4 488 12 16 20 24 28 32 36 40 44
Visit (Wk)
0.1
1
10
PlasmaCAB(μg/mL)*
CAB (n = 278)
PA-IC90 (0.166 µg/mL)
4 488 12 16 20 24 28 32 36 40 44
Visit (Wk)
10
100
PlasmaRPV(ng/mL)*
RPV (n = 278)
PA-IC90 (12 ng/mL)
*Median (5th, 95th percentile) concentration–time data.

7. FLAIR: Adverse Events
Orkin. CROI 2019. Abstr 140LB. Slide credit: clinicaloptions.com
AEs, n (%) LA CAB + LA RPV (n = 283) DTG/ABC/3TC (n = 283)
AEs occurring in ≥ 10% of patients
 Any event (per patient)
•Nasopharyngitis
•Headache
•Upper RTI
•Diarrhea
246 (87)
56 (20)
39 (14)
38 (13)
32 (11)
225 (80)
48 (17)
21 (7)
28 (10)
25 (9)
Drug-related AEs occurring in ≥ 3% of patients
 Any event (per patient)
•Headache
•Pyrexia
79 (28)*
14 (5)
13 (5)
28 (10)
4 (1)
0
Drug-related serious AEs 1 (< 1)† 0
AEs leading to discontinuation 9 (3)‡ 4 (1)§
*94% (74/79) were grade 1/2. †Right knee monoarthritis. ‡Hepatitis B (n = 2); acute hepatitis A, acute hepatitis A/secondary syphilis, hepatitis C,
increased transaminases, injection-site pain, injection-site pain/general discomfort/diarrhea/vomiting, adenocarcinoma of colon (n = 1 each).
§Fatigue/nausea/dizziness, amnesia/disturbance in attention/dysarthria, suicide attempt, renal failure (n = 1 each).

8. FLAIR: Injection-Site Reactions
 99% of ISRs were grade 1/2,
88% resolved within 7 days
Orkin. CROI 2019. Abstr 140LB. Reproduced with permission. Slide credit: clinicaloptions.com
*No grade > 3 events reported. †2 additional patients d/c
for injection intolerability.
ISR Incidence Over Time
Characteristic to Wk 72
LA CAB + LA RPV
(n = 283)
Patients receiving injections, n 278
Injections given, n 7704
ISR events, n (%)
 Pain
 Nodule
 Induration
 Swelling
 Warmth
 Grade 3 ISR pain*
2203 (28.6)
1879 (85.3)
86 (3.9)
82 (3.7)
38 (1.7)
38 (1.7)
12 (< 1.0)
Median duration of ISRs, days 3
ISR pain leading to d/c,† n (%) 2 (< 1.0)
ParticipantsWithISRs(%)
Study Wk
100
80
60
40
20
0
4 8 12 16 20 24 28 32 36 40 44 48
71
43 38
32 31 33 29 27 27
34
24 20

9. FLAIR: Patient-Reported Outcomes
Orkin. CROI 2019. Abstr 140LB. Slide credit: clinicaloptions.com
‡Per single question in Wk 48 participant survey.
Drug Delivery Preference
of Patients in CAB + RPV Arm
Patient Satisfaction With
Regimen at Wk 48 vs Oral Induction
HIVTSQc
Mean Total
Score*
Switch to LA
CAB + LA RPV
(n = 263)
Continue
DTG/ABC/3TC
(n = 266)
Wk 48† 29.6 25.5
Population
Preferred Regimen,‡ % (n/N)
Long-Acting IM Daily PO
ITT-E 91 (257/238) 1 (2/238)
Responding
participants
99 (257/259) NA*Scores can range from -33 to +33.
†Difference: 4.1 (95% CI: 2.8-5.5; P < .001).

10. FLAIR: Conclusions
 Following 20-wk induction with DTG/ABC/3TC in ART-naive patients, switch to LA
CAB + LA RPV noninferior to continued BL ART at Wk 48
‒ HIV-1 RNA ≥ 50 copies/mL in 2.1% vs 2.5%, respectively
‒ Treatment difference: -0.4% (95% CI: -2.8% to 2.1%)
‒ HIV-1 RNA < 50 copies/mL in 93.6% vs 93.3%, respectively
‒ Treatment difference: 0.4% (95% CI: -3.7% to 4.5%)
‒ Confirmed VF in 1.4% vs 1.1%, respectively
‒ NNRTI + INSTI resistance with all 3 cases in CAB + RPV arm; none in DTG/ABC/3TC arm
 In CAB + RPV arm, most drug-related AEs (94%) and ISRs (99%) were grade 1/2
 Patient-reported satisfaction significantly higher in CAB + RPV arm
Orkin. CROI 2019. Abstr 140LB. Slide credit: clinicaloptions.com

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