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Switch to EVG/c/FTC/TDF - PowerPoint Presentation

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Switch to EVG/c/FTC/TDF - PPT Presentation

STRATEGYPI Study STRATEGYNNRTI Study Design Endpoints Primary proportion of patients maintaining HIV RNA lt 50 cmL at W48 mITT snapshot noninferiority if lower margin of a twosided 95 CI for the difference 12 85 power If noninferiority and lower margin gt 0 assessme ID: 616654

ftc nnrti strategy switch nnrti ftc switch strategy evg tdf study hiv group 590 2014 infect lancet pozniak dis

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Slide1

Switch to EVG/c/FTC/TDF

STRATEGY-PI

Study

STRATEGY-NNRTI

StudySlide2

Design

Endpoints

Primary: proportion of patients maintaining HIV RNA < 50 c/mL at W48 (mITT, snapshot) ; non-inferiority if lower margin of a two-sided 95% CI for the difference = -12%, 85% power. If non-inferiority and lower margin > 0, assessment for superiority

Secondary: proportion of patients maintaining HIV RNA < 50 c/mL at W48 (TLOVR algorithm), CD4, safety, tolerability to W96

Switch to EVG/c/FTC/TDF

Continue NNRTI + FTC + TDF

Pozniak A. Lancet Infect Dis 2014;14:590-9

STRATEGY-NNRTI

Randomisation*

2 : 1Open-label

HIV+ ≥ 18 yearsOn FTC + TDF + NNRTI HIV RNA < 50 c/mL > 6 monthsNo virologic failureGenotype testing before ART withno resistance to study drugsIntegrase inhibitor naïveeGFR > 70 mL/mim

N = 147

N = 292

W48

W96

* Randomisation stratified by EFV use at screening

STRATEGY-NNRTI Study: Switch NNRTI to EVG/cSlide3

STRATEGY-NNRTI Study: Switch NNRTI to EVG/c

EVG/c/FTC/TDF

N = 291

NNRTI + FTC + TDF

N = 143

Median age, years

43

39

Female

8%

6%

Time since HIV diagnosis, median years

5

5

On first ARV regimen

90%

91%

NNRTI at randomisation

Efavirenz

(

coformulated

EFV/FTC/TDF)

80% (76%)

74% (70%)

Nevirapine16%19%Rilpivirine3%7%Etravirine1%0CD4 cell count (/mm3), median561562Hepatitis B / hepatitis C coinfection2% / 4%2% / 1%Discontinuation by W482218

Pozniak A. Lancet Infect Dis 2014;14:590-9

STRATEGY-NNRTI

Baseline characteristics and patient dispositionSlide4

Virologic outcome at W48 (mITT, snapshot)

93

88

Difference (95% CI)

= 5.3% (-0.5 to 12.0)

1

1

N = 3

N = 1

6

11

Pozniak A. Lancet Infect Dis 2014;14:590-9

STRATEGY-NNRTI

EVG/c/FTC/TDF

NNRTI + FTC + TDF

%

0

20

406080

100

HIV RNA

< 50 c/mL

HIV RNA

≥ 50 c/mL

No virologicdataSTRATEGY-NNRTI Study: Switch NNRTI to EVG/cSlide5

Pozniak A. Lancet Infect Dis 2014;14:590-9

STRATEGY-NNRTI

HIV RNA < 50 c/mL

Sensitivity and secondary analysis

EGV/c/FTC/TDF

NNRTI + FTC + TDF

Per-proctol

99%

99%

Difference

: 0.1% (95% CI: - 2.1 to 3.5)

ITT-TLOVR

92%

87%

Difference

: 5.0% (95% CI: -1.1 to 12.1)

One participant in each group met the criteria for resistance testing (HIV RNA

>

400 c/mL at virologic failure or early discontinuation)

No emergence of resistance

Both remained on study treatment and achieved HIV RNA < 50 c/mL after W48

STRATEGY-NNRTI Study: Switch NNRTI to EVG/cSlide6

Virologic sucess overall and by subgroup at W48 (mITT)

Pozniak A. Lancet Infect Dis 2014;14:590-9

STRATEGY-NNRTI

Overall

Age < 40

years

Age

>

40

years

Male

Female

White

Non-white

Efavirenz

Non-

efavirenz

On first

regimen

at

baseline

On second

regimen

at

baseline010203040

50

60

70

80

90

100

Virological

success

(%)

271/290

126/143

107/114

62/74

164/176

64/69

251/267

119/134

20/23

7/9

216/230

99/109

55/60

27/34

214/231

91/106

57/59

35/37

245/262

114/130

25/27

11/12

n/N

Favours

not

switching

Switch group

No-switch group

-20

-10

0

10

20

30

40

50

Difference

(%)

Favours

switching

STRATEGY-NNRTI Study: Switch NNRTI to EVG/cSlide7

Adverse events and grade 3-4 laboratory abnormalities

* neuromuscular symptoms, suicide, dysgueusia, prurigo, Fanconi syndrome, increased creatinine

** altered mood

Pozniak A. Lancet Infect Dis 2014;14:590-9

STRATEGY-NNRTISTRATEGY-NNRTI Study: Switch NNRTI to EVG/c

EVG/c/FTC/TDF

NNRTI + FTC + TDF

Any

adverse

event

,

81%

75%

Grade 3 or 4 AE

7%

6%

Serious

adverse

event

5%

4%

Discontinuation because of AE

N = 6 (2%)*

N = 1 (1%)**

Death

N = 1

0

AE occurring more frequently in one group

14%

23%

Headache

(p = 0.03)

3%

1%

Nausea

(p = 0.05)

2%

6%

Cough

(p= 0.04)

2%

1%

Fatigue (p = 0.02)

2%

1%Slide8

STRATEGY-NNRTI Study: Switch NNRTI to EVG/c

Other safety data

Incidence and prevalence of headache and nausea became similar between groups by week 12

Grade 3-4 laboratory abnormalities : 10% in the switch group vs 14% in the no-switch groupCreatinine increase in switch group at week 4, stabilizing up to week 48 (median +11 mmol

/L)Small decrease in HDL-cholesterol in the switch group vs no change in the no-switch groupIn the subgroup switched form EFV + FTC + TDF to EVG/c/FTC/TDFImprovement in lipidsHIV Symptom Index : improvement of CNS symptomsHigher treatment satisfaction score at W4 and W24Pozniak A. Lancet Infect Dis 2014;14:590-9

STRATEGY-NNRTISlide9

STRATEGY-NNRTI Study: Switch NNRTI to EVG/c

Conclusion

Coformulated

EVG/c/FTC/TDF is non-inferior to continuing an existing regimen of NNRTI plus FTC and TDF in virologically suppressed, HIV-infected adults with no history of virological failure or resistance to FTC or TDF.Low frequency of virologic

failure and absence of emergent resistance in the group switched to EVG/c/FTC/TDF Rare discontinuations because of adverse eventsFatigue, cough, headache and nausea were more frequent in the switch group ; Rates of CNS symptoms decreased in patients switched from EFVIncrease in creatinine similar to that of phase 3 of EGV/c/FTC/TDFModerate improvement in lipids in patients switched from EFVEVG/c/FTC/TDF is a switch option in virologically suppressed patients with no history of virological failure on an NNRTI regimen, when its continuation is not suitable

Pozniak A. Lancet Infect Dis 2014;14:590-9STRATEGY-NNRTI