Switch to NNRTI Switch to DOR/3TC/TDF - PowerPoint Presentation

Slide1

Switch to NNRTI

Switch to DOR/3TC/TDF

DRIVE-SHIFT

Study

Design

EndpointsPrimary: % of patients maintaining HIV RNA < 50 c/mL (ITT-snapshot) ; non-inferiority of DOR/3TC/TDF at W48 (and at W24) compared to continuation of cART at W24 if lower margin of a two-sided 95% CI for the adjusted difference = - 8%Secondary : % of patients with HIV RNA ≥ 50 c/mL: non-inferiority of DOR/3TC/TDF at W48 (and at W24) compared to continuation of cART at W24, non-inferiority margin of 4%

DOR/3TC/TDF

Continuation of cART

DRIVE-SHIFT

Randomisation *

2:1Open-label

HIV+ ≥ 18 yearsHIV RNA < 40 c/mL ≥ 6 monthsOn 2 NRTI + PI/b or EVG/c or NNRTINo prior virologic failureNo major resistance mutationto DOR, 3TC or TDFeGFR ≥ 50 mL/min

N = 223

N = 447

W24

W48

DRIVE-SHIFT

Study

: Switch to DOR/3TC/TDF

DOR/3TC/TDF

Johnson M. J

Acquir

Immune

Defic

Syndr

. 2019 Apr 11. [

Epub

ahead of print]

DOR/3TC/TDFN = 447Continuation cARTN = 223Mean age, years4342Female, %1713Race: white, %7775CD4/mm3, mean665650Baseline cART, %Boosted PIEVG/cNNRTI7162470525Discontinuation by W24, N (%)Adverse eventLack of efficacyInvestigator decisionConsent withdrawalLost to follow-upProtocol deviationDeathDiscontinued at W48, N (%)Adverse eventLack of efficacy20 (4.4%)702631120/427 continued (4.6%)6514 (6.3%)11314407/209 deferred switch (3.3%)21

Baseline characteristics and patient disposition

DRIVE-SHIFT

DRIVE-SHIFT Study: Switch to DOR/3TC/TDF

Johnson M. J

Acquir

Immune

Defic

Syndr

. 2019 Apr 11. [

Epub

ahead of print]

Primary endpoint: efficacy at 2 different time points, ITT Snapshot

0

20

40

60

80

100

%

93.7

94.6

DOR/3TC/TDF immediate switch W48

Continuation cART W24

Immediate switch W24

447

223

447

223

90.8

94.6

HIV RNA

< 50 c/

mL

1.6

1.8

HIV RNA

> 50 c/

mL

1.8

≠ - 3.8%

(IC 95 %: - 7.9 to 0.3)

≠ - 0.9%

(- 4.7 to 3.0)

≠ - 0.2%

(- 2.5 to 2.1)

≠ 0%

(- 2.3 to 2.3)

1.8

HIV RNA

< 50 c/

mL

HIV RNA

> 50 c/

mL

Primary time point

Secondary time point

DRIVE-SHIFT

DRIVE-SHIFT

Study

: Switch to DOR/3TC/TDF

Johnson M. J

Acquir

Immune

Defic

Syndr

. 2019 Apr 11. [

Epub

ahead of print]

DRIVE-SHIFT Study: Switch to DOR/3TC/TDF

Resistance analysis population, DOR/3TC/TDF immediate and deferred switchProtocol-defined virologic failure, N = 7Discontinuation without protocol-defined virologic failure, N = 40No participant developed DOR or NRTI resistanceAll 24 participants with baseline NNRTI mutations (K103N, Y181C, G190A) remained suppressed

Drug resistance

DRIVE-SHIFT

Johnson M. J

Acquir

Immune

Defic

Syndr

. 2019 Apr 11. [

Epub

ahead of print]

DOR/3TC/TDFN = 447Continuation cART N = 223Any adverse event, %68.952.5Drug-related adverse event, %19.52.2Most common drug-related adverse event Headache, %1.60.4Discontinuation due to adverse event, %Due to drug-related adverse event, %2.51.60.40Mean change from baseline in fasting lipids (baseline boosted PI group), mg/dLLDL-cholesterol- 16.5 *- 1.9 *Non HDL-cholesterol- 24.7 *- 1.3 *

Adverse events, W24

* p < 0.0001

DRIVE-SHIFT Study: Switch to DOR/3TC/TDF

DRIVE-SHIFT

Johnson M. J

Acquir

Immune

Defic

Syndr

. 2019 Apr 11. [

Epub

ahead of print]

ConclusionSwitching to DOR/3TC/TDF demonstrated non-inferior efficacy, at W24 and W48, compared to continuation of baseline cART through W24No emergence of resistance to DOR, 3TC or TDFFavorable safety profileHigher incidence of adverse events in participants who switched to DOR/3TC/TDF compared with those who continued their baseline regimenSuperior lipid profile for LDL-cholesterol and non-HDL cholesterol of DOR/3TC/TDF compared to continuation of a boosted-PI regimen

DRIVE-SHIFT Study: Switch to DOR/3TC/TDF

DRIVE-SHIFT

Johnson M. J

Acquir

Immune

Defic

Syndr

. 2019 Apr 11. [

Epub

ahead of print]