2019 Ryan White HIV/AIDS Program CLINICAL CONFERENCE

ATLAS/FLAIR Week 48 Pooled Results

Virologic outcomes

Adjusted treatment difference (95% CI)*

94.4

100

93.1

CAB+RPVLA

CAR

Primary Endpoint:

CAB + RPV LA (n=591) CAR (n=591)

LA noninferior to CAR (HIV-1 RNA ≥50 c/mL) atWeek 48

0.2

80

4% NI margin

-1.4 1.7

60

Difference (%) -10 -8 -6 -4 -2 0 2 4 6 8 10

40

Key Secondary Endpoint:

CAR

CAB+RPVLA

20

-1.4

5.1

3.9

1.9

1.7

LA noninferior to CAR (HIV-1 RNA <50 c/mL) atWeek 48

−10% NI margin

0

-4.1

1.4

Virologic Nonresponse (≥50 c/mL)

Virologic Success (<50 c/mL)

No Virologic Data

Proportion of Participants (%)

Difference (%) -10 -8 -6 -4 -2 0 2 4 6 8 10

*Adjustedforsexandbaselinethirdagentclass.

Overton E, IAS2019MOPEB257; SwindellsS, CROI2019;#139;OrkinC,CROI2019;#140.

CAB,cabotegravir;CAR,currentantiretroviral;CI,confidence interval; ITT-E, intention-to-treatexposed;LA, long-acting;NI,noninferiority;RPV,rilpivirine.

Slide13of 44FromRTGandhi, MD atNewOrleans, LA,December 4-7, 2019, Ryan WhiteHIV/AIDS ProgramCLINICAL CONFERENCE, IAS  USA.

Treatment Emergent Resistance (CAB/RPV Groups)

BaselineResistance (HIV DNA)

Resistanceat Virologic failure

Site/HIV subtype

RT

IN

RT

IN

ATLAS Russia/A1

E138E/A

L74I

E138A

L74I

France/AG

V108V/I, E138K

None

V108I, E138K

None

Russia/A1

None

I74I

E138E/K N155H, L74I

FLAIR

Russia/A1

None

L74I

E138E/A/K/T L74I, Q148R

Russia/A1

None

L74I

K101E

L74I, G140R

Russia/A1

None

L74I

E138K

L74I, Q148R

L74Imore common inpeoplewithHIV subtypeAbutdidnotaffect treatment response. CAB, RPV conc at time of failurebelowpopulationmeans butwithin range formajoritywhomaintained suppression.

Overton E IAS2019MOPEB257;SwindellsS,etal.CROI2019;#139;OrkinC,etal.CROI2019;#140.

Slide14of 44FromRTGandhi, MD atNewOrleans, LA,December 4-7, 2019, Ryan WhiteHIV/AIDS ProgramCLINICAL CONFERENCE, IAS  USA.

LA CAB/RPV: Questions

• Is the 4-week oral lead-in needed? What about direct to inject? • What about the long tail in people who stop the drugs? CAB detectable up to 48 wks after single injection, longer in women • Will the drugs be useful in people who have difficulty adhering to oral ART? • Can LA CAB/RPV be used in someone who is viremic? ▫ Case: person with bowel resection; not able to absorb oral ART; suppressed on IM CAB/RPV • What will the cost of the drugs be? Will the cost of the administration be reimbursed? OrkinC,IAS2019TUSY0403;Landovitz,R,HIVR4P,Madrid, 2018.Abstract#OA15.06LB;SamanR, EACS2019

Slide15of 44FromRTGandhi, MD atNewOrleans, LA,December 4-7, 2019, Ryan WhiteHIV/AIDS ProgramCLINICAL CONFERENCE, IAS  USA.