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Comparison of INSTI vs PI Comparison of INSTI vs PI

Comparison of INSTI vs PI - PowerPoint Presentation

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Comparison of INSTI vs PI - PPT Presentation

FLAMINGO GS2360103 ACTG A5257 WAVES ARIA Squires K Lancet HIV 2016 39e410e420 Design Objective Non inferiority of EVGCFTCTDF at W48 HIV RNA lt 50 c mL by intention to treat snapshot analysis lower margin of the 2sided 95 CI for the difference 12 ID: 621282

tdf ftc hiv evg ftc tdf evg hiv waves rna atv squires 100 000 women study lancet 2016 e410

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Slide1

Comparison of INSTI vs PI

FLAMINGO

GS-236-0103

ACTG A5257

WAVES

ARIA Slide2

Squires K. Lancet HIV 2016; 3(9):e410-e420

Design

Objective

Non inferiority of EVG/C/FTC/TDF at W48: % HIV RNA < 50 c/

mL

by intentionto treat, snapshot analysis (lower margin of the 2-sided 95% CI for the difference = -12%)

EVG/C/FTC/TDF 150/150/200/300 mg QDATV + r + TDF/FTC placebo

ATV + r 300/100 mg + FTC/TDF QDEVG/C/FTC/TDF placebo

Randomisation*1 : 1Double-blind

WomenARV-naïveHIV RNA > 500 c/mLAny CD4 cell countSensitivity to FTC, TDF and ATVeGFR > 70 mL/min

*Randomisation was stratified by HIV RNA (< 100,000 or 100,000-400,000 or > 400,000 c/mL) at screening and race (black or non-black)

Study WAVES: EVG/C/FTC/TDF QD vs ATV + r + FTC/TDF QD in Women

N = 286

N = 289

W48

WAVES

Open-label

extensionSlide3

EVG/C/FTC/TDF

N = 289

ATV + r + FTC/TDF

N = 286

Female

100%

100%

Median age, years

34

35White / Black / Asian

44% / 50% / 3%

42% / 47% / 6%

AIDS

4%

5%

HIV RNA (log

10

c/

mL

), median (Q1-Q3)

4.46 (4.09-4.97)

4.56 (4.02-5.00)

HIV RNA 100,000-400,000 c/mL

HIV RNA ≥ 400,000 c/mL15%9%18%8%CD4 cell count (/mm3), median344370CD4 < 200 per mm317%18%Hepatitis B / hepatitis C coinfection4% / 8%3% / 9%Discontinuation by W48, N (%)29 (10%)45 (16%)For lack of efficacyN = 0N = 1For adverse eventN = 5N = 19Lost to follow-up / Withdrew consentN = 12 / N = 6N = 12 / N = 5Non-compliance / OtherN = 4 / N = 2N = 5 / N = 3

Baseline characteristics and patient disposition

Study WAVES: EVG/C/FTC/TDF QD vs ATV + r + FTC/TDF QD in Women

WAVES

Squires K. Lancet HIV 2016; 3(9):e410-e420Slide4

Response to treatment at week 48

Mean CD4/mm

3

increase at W48 :

+ 221

(EVG/C/FTC/TDF) vs+ 212 (ATV + r + FTC/TDF)

EVG/C/FTC/TDF (N = 289)ATV + r + FTC/TDF (N = 286)HIV RNA < 50 c/mL (ITT, snapshot)

25501007587

81

Adjusted difference(95% CI) = 6.5 % (0.4 ; 12.6)p = 0.034912

Virologic success

Virologic failure%

0

4

7

No virologic

data

Study WAVES

: EVG/C/FTC/TDF QD vs ATV + r

+ FTC/TDF QD in Women

WAVES

Squires K. Lancet HIV 2016; 3(9):e410-e420Slide5

HIV RNA < 50 c/

mL

at W48 by baseline HIV RNA and CD4 count

EVG/C/FTC/TDF

ATV + r + FTC/TDF

25

5010075

8781%8682

Overall

< 100,00008882

<

350> 350

86

79

> 100,000

HIV

RNA (copies/mL)

CD4 cell count (/mm

3

)

90

78

286

2862202146972146131143154Squires K. IAS 2015 Vancouver, Abs. MOLBPE08 ; Squires K. Lancet HIV 2016; 3(9):e410-e420Study WAVES: EVG/C/FTC/TDF QD vs ATV + r + FTC/TDF QD in WomenWAVESSlide6

Emergence of resistance

EVG/C/FTC/TDF

ATV

+

r + FTC/TDF

Resistance

analysis population1921

Final RAP*712Resistance mutations emergence

0

3NRTI-resistance1

3D67D/N

1

0

M184V/I

0

3

K65R

0

0

INSTI-resistance

0

0

Primary PI-resistance

00* Criteria :Suboptimal response (HIV RNA ≥ 50 c/mL and < 1 log10 reduction from baseline by W8, confirmed)Virologic rebound (> 400 c/mL after achieving HIV RNA < 50 c/mL, or 2 consecutive visits with > 1 log10 increase from nadir)HIV RNA > 400 c/mL at W48Exclusion of patients with HIV RNA < 50 c/mL at subsequent visitsStudy WAVES: EVG/C/FTC/TDF QD vs ATV + r + FTC/TDF QD in WomenWAVESSquires K. Lancet HIV 2016; 3(9):e410-e420Slide7

EVG/C/FTC/TDF

ATV + r + FTC/TDF

p

DXA assessment

at baseline, spine ; hip, N

at W48, spine ; hip, N

138 ; 120

136 ; 118

150 ;128

150 ; 128

Median change from baseline in BMD

Lumbar spine

- 3.23 %

- 3.28 %

0.69

Hip

- 2.99 %

- 2.68 %

0.37

Median change from baseline in

eGFR

(

mL

/min), Cockroft-Gault formula- 6.1- 2.40.15Renal and bone mineral density (DXA) assessmentsEVG/C/FTC/TDFATV + r + FTC/TDFpTotal cholesterol+ 7+ 20.02Other lipid parameters (LDL-c, HDL-c, Triglycerides, Total cholesterol:HDL-cholesterol rationsMedian change from baseline in fasting lipids (mg/dL)Study WAVES: EVG/C/FTC/TDF QD vs ATV + r + FTC/TDF QD in WomenWAVESSquires K. Lancet HIV 2016; 3(9):e410-e420Slide8

EVG/C/FTC/TDF

ATV + r + FTC/TDF

Adverse events leading to discontinuation, N

5 discontinuations

19 discontinuations

Hepatobiliary disorder

1

4

Gastro-intestinal disorder

3

4

Pulmonary tuberculosis

1

0

Renal

0

2

Skin disorder

2

9

Drug hypersensitivity

0

1

Adverse event in ≥ 10% of patients, %0Headache1615Upper respiratory tract infection1615Nausea1514Vomiting1014Jaundice / Icterus< 1 / < 111 / 12Grade 3-4 laboratory abnormalities in ≥ 2%, %

Serum amylase elevation

2

2

Neutropenia < 1000/mm

3

2

3

ALT elevation

2

2

Hyperbilirubinemia

< 1

46

Glycosuria

0

2

A

dverse events and Grade 3-4 laboratory abnormalities

Study

WAVES

: EVG/C/FTC/TDF QD

vs

ATV + r

+ FTC/TDF QD in Women

WAVES

Squires K. Lancet HIV 2016; 3(9):e410-e420Slide9

Summary

EVG/C/FTC/TDF QD was

virologically

non inferior and superior to ATV + r + FTC/TDFSimilar virologic

response of the 2 regimens in different subgroups of patients, including those with high HIV RNA or CD4 < 350/mm

3 at enrolmentDevelopment of major resistance mutations occurred inNo patients on EVG/C/FTC/TDF3 patients on ATV + r + /FTC/TDF: NRTI mutations, no PI mutationsDiscontinuation because of adverse events was lower with EVG/C/FTC/TDF

Less incidence of icterus and hyperbilirubinemia with EVG/C/FTC/TDF Comparable changes in fasting lipids in both groups, except for total cholesterol which elevation was higher with EVG/C/FTC/TDF Median decreases in estimated glomerular filtration rate and in spine and hip BMD were modest and not different between the 2 groupsStudy WAVES: EVG/C/FTC/TDF QD vs ATV + r + FTC/TDF QD in WomenWAVES

Squires K. Lancet HIV 2016; 3(9):e410-e420