Switch to Dolutegravir plus Rilpivirine dual therapy in ...regist2.virology-education.com/2016/14EU/04_Sterrantino.pdf · Switch to Dolutegravirplus Rilpivirine dual therapy in cART-Experienced

Switch to Dolutegravir plus Rilpivirinedual therapy in cART-Experienced

Subjects: an Italian cohort

Gaetana SterrantinoAzienda Ospedaliero-Universitaria Careggi

Infectious diseases, Florence, Italy

Background• Little information is available about the efficacy and safety of the

combination of rilpivirine (RPV) plus dolutegravir (DTG).

• The purpose of this work is to show the results of this regimen in clinical practice.

Methods• All experienced HIV-1 infected subjects treated with DTG plus RPV in eight

italian centers were included between October 2014 and September 2015 in an observational cohort named TivEdO (Tivicay plus Edurant Observational Cohort).

• CD4+ cell counts, HIV-RNA and creatinine values were collected at baseline and at weeks 4, 12, 24 and 48.

• Patients were stratified by the baseline viral load into three groups: more than 50 copies per mL, less than 50 copies per mL but quantifiable RNA, and virus no detected (NVD).

Number (%) Median (range)

Females/males 42/90 (31.7-68.3)Age, years 53 (29-77)Non-caucasians 10 (7.6)Baseline CD4+ cell count (cells/μL) 708 (69-2615)

HIV-RNA, copies/mL•NVD•50

89 (54.9)27 (20.5)16 (12.1)

Risk of transmission:Sexual transmissionIDUOther

91 (68.9)39 (29.5)

2 (1.5)At least 1 failure in previous regimens 57 (43.2)

Follow-up (weeks) 29 (24-71)

Baseline patient demographics, 132 subjects

n. o

f sub

ject

sREASONS TO SWITCH

13 Osteopenia/osteoporosis12 Hyperlipemia7 GI intolerance5 CV problems4 Glucose intolerance4 Mental disturbances1 Liver toxicity

Grafico1

Simplification

Toxicity

DAA interaction

LL viremia

Adherence

70

46

7

5

4

TivEdO

TivEdO

Sesso:M: 70, F: 42

Età:

media51.8

mediana53

range29 - 77

DS9.7

Rischio:

TD29.5%39

Het33.3%44

MSM35.6%47

Vert0.8%1

Trasf0.8%1

Switch da (sett)

media30.5

mediana29

range24 - 71

DS10.5

Motivi switch

semplificazione53.0%70

tossicità34.8%46% tossicità% del totale

28.3%13osteopenia/porosi9.8%

26.1%12iperlipidemia9.1%

15.2%7intolleranza GE5.3%

10.9%5alterazioni cardiovascolari3.8%

8.7%4intolleranza glucosio3.0%

8.7%4disturbi mentali3.0%

2.2%1epatotossicità0.7%

interazioni con DAA5.3%7

LLV3.8%5

Aderenza2.3%3

Fallimento0.8%1

Terapia pre-

a un farmaco0.0%0RAL39.4%52

a 2 farmaci31.1%41TDF35.6%47

a 3 farmaci67.3%89FTC34.8%46

8.3%11Triple class3TC26.5%35

8.3%112NA+INSTIDRV/r25.0%33

31.1%412NA+NNRPV22.0%29

18.2%242NA+PIATV/r19.7%26

> 3 farmaci1.6%2ABC17.4%23

ETV15.9%21

EFV8.3%11

NVP8.3%11

MVC4.5%6

AZT4.5%6

ATV4004.5%6

LPV/r3.1%4

ELV/c3.1%4

Fallimento pre-43.2%57

RAMs basali

nessuna56.8%75RTProINSTI

a una classe12.1%162270.8%1932.3%32130.8%1

a 2 classi20.5%272252.3%3907.6%101480.8%1

a 3 classi10.6%142211.6%2892.3%31400.8%1

a > 3 classi0.0%02194.5%6882.3%31271.6%2

2180.8%1842.3%31240.8%1

21515.9%21823.1%41230.8%1

2105.3%7776.8%9740.8%1

2083.1%4742.3%3720.8%1

1900.8%1730.8%1540.8%1

18420.5%27718.3%11

1812.3%3700.8%1

1790.8%1693.1%4

1511.6%26321.3%28

1183.8%5622.3%3

1150.8%1602.3%3

1081.6%2580.8%1

1036.8%9463.8%5

1010.8%1450.8%1

1001.6%23614.4%19

980.8%1352.3%3

900.8%1331.6%2

750.8%1303.8%5

740.8%1240.8%1

706.1%8206.1%8

692.3%3161.6%2

676.8%9150.8%1

652.3%3138.3%11

442.3%31015.1%20

4114.4%19

OverallCD4 T0%/mmcCD4 W24

media32.3%722media32.9%741

mediana31.8%708mediana32.7%729

range7,6% - 64,2%69 - 2615range6,3% - 57,1%100 - 2338

DS9.7%421DS9.3%445

Subp W48CD4 T0%/mmcCD4 W24CD4 W48

media31.4%697media31.2%701media31.0%707

mediana30.2%688mediana30.5%696mediana31.2%719

range7,6% - 50,9%69 - 1352range6,3% - 49,2%100 - 1327range4,4% - 53%57 - 1539

DS9.1%456DS8.7%462DS9.2%449

OverallHIV RNA T0HIV RNA W4HIV RNA W24

NVD54.9%89NVD86.4%114NVD84.8%112

< 50 D20.5%27< 50 D11.4%15< 50 D14.4%19

> 5012.1%16> 502.3%3> 500.8%1

media (log10)2.67media1.71media

mediana5.09mediana1.71mediana4.17

range1,74 - 5,98range1,69 - 1,75range

DS3.21DS0.04DS

Subp W48HIV RNA T0HIV RNA W4HIV RNA W24HIV RNA W48

NVD54.5%24NVD77.3%34NVD84.1%37NVD88.6%39

< 50 D31.8%14< 50 D18.2%8< 50 D13.6%6< 50 D9.1%4

> 5013.6%6> 504.5%2> 502.3%1> 502.3%1

media (log10)4.45media1.73mediamedia

mediana4.41mediana1.73mediana3mediana4.17

range3,19 - 5,49range1,71 - 1,75rangerange

DS1.98DS0.02DSDS

creatinina T0creatinina W24proteinuria T0proteinuria W24

media0.89media0.97media1.04media0.54

mediana0.86mediana0.9mediana0mediana0

range0,50 - 2,10range0,52 - 2,50range0 - 50range0 - 15

DS0.24DS0.26DS5.86DS2.25

Fallimenti0.8%1RAMS nuoveRT

138Q1

181C1

Tivista

Tivista

Sesso:M: 83, F: 30

Età:

media51.4

mediana51

range24 - 82

DS8.59

Rischio:

TD28.3%32

Het23.9%27

MSM46.0%52

Vert1.6%2

Switch da (sett)

media47

mediana44

range24 - 234

DS83.5

Motivi switch


tossicità15.0%17% tossicità% totale


11.8%2lipodistrofia1.8%


5.9%1tossicità gastrointestinale0.9%

5.9%1diabete0.9%

5.9%1rialzo CPK0.9%

5.9%1tossicità renale0.9%

LLV5.3%6

Aderenza3.5%4

Progressione2.6%3

Fallimento27.4%31

Terapia pre-

da TI1.8%2

a un farmaco0.9%1DRV/r67.2%76

a 2 farmaci37.2%42RAL48.7%55

a 3 farmaci54.0%61TDF37.2%42

26.2%16Triple classFTC37.2%42

8.2%52NA+INSTI3TC27.4%31

18.0%112NA+NNABC22.1%25

45.9%282NA+PIETV18.6%21

ATV/r16.8%19

> 3 farmaci6.2%7MVC15.0%17

RPV14.1%16

LPV/r7.1%8

EFV6.2%7

ATV4001.8%2

ddI1.8%2

DTG0.9%1


RAMs basali


a una classe8.8%102310.9%19313.3%151560.9%1

a 2 classi22.1%252300.9%19041.6%471555.3%6

a 3 classi50.4%572280.9%18814.2%161540.9%1

a > 3 classi8.0%92270.9%1851.8%21510.9%1

2254.4%58434.5%391480.9%1

2212.6%38232.7%371430.9%1

21923.0%267732.7%371400.9%1

21552.2%59743.5%41350.9%1

21030.0%34737.1%81271.8%2

2085.3%67136.3%41

1930.9%1695.3%6

19010.6%126347.8%54

1884.4%56210.6%12

18444.2%50606.2%7

18119.5%22580.9%1

1797.1%8564.4%5

1514.4%55429.2%33

1385.3%6535.3%6

11810.6%12489.7%11

1162.6%34631.9%36

1154.4%5431.8%2

10810.6%123637.2%42

1064.4%5339.7%11

10328.3%32308.0%9

10111.5%13242.6%3

10014.2%16193.5%4

9812.4%142031.9%36

909.7%11165.3%6

770.6%2156.2%7

758.8%101319.5%22

7415.9%181048.7%55

7015.0%17

695.3%6

6715.0%17

656.2%7

623.5%4

470.9%1

448.8%10

4138.9%44


media32.3%628media32.9%655


range3,3% - 46,5%17 - 1693range6,9% 46,6%36 - 1652

DS9.5%332DS8.5%347




range8% - 43%157 - 1287range9% - 43,4%125 - 1321range11% - 43,7%139 - 1583

DS11.3%342DS10.8%367DS8.7%351


NVD37.2%42NVD55.7%63NVD73.4%83

< 50 D20.3%23< 50 D27.4%31< 50 D20.3%23

> 5043.4%49> 5016.8%19> 506.2%7

media3media2.42media2.4


range1,74 - 5,3range1,72 - 4,55range1,91 - 2,9

DS0.82DS0.79DS0.49


NVD37.7%20NVD60.4%32NVD71.7%38NVD83.0%44

< 50 D22.6%12< 50 D26.4%14< 50 D20.7%11< 50 D15.1%8

> 5039.6%21> 5012.5%7> 507.5%4> 501.9%1

med+E128:V131ia (log10)4.45media1.73media2.05media

mediana2.49mediana2.36mediana1.93mediana1.7

range1,72 - 4,67range1,91 - 3,01range1,84 - 2,38range

DS0.8DS0.63DS0.24DS





DS0.22DS0.21DS19.2DS19.4

Fallimenti0.8%1RAMS nuove0

Foglio3

tivedo

Motivi switch











LLV3.8%5

Aderenza2.3%3

Fallimento0.8%1

Simplification70

Toxicity46

DAA interaction7

LL viremia5

Adherence4

Foglio3

Patients’ baseline disposition towards antiretrovirals

0

10

20

30

40

50

60

70

80

90

0 0

41

89

2

0 1 2 3 > 3

Complexity of the former regimen

n. p

atie

ntsp

er c

ompl

exity

of re

gim

en

n. drugs in previous regimen

0 10 20 30 40 50 60

RALTDFFTC3TC

DRV/rRPV

ATV/rABCETVEFVNVP

MVCAZT

ATV400LPV/rELV/c

Antiretrovirals in the former regimen

n. of patients

Grafico1

n. drugs in previous regimenn. drugs in previous regimenn. drugs in previous regimenn. drugs in previous regimenn. drugs in previous regimen

0

1

2

3

> 3

0

0

41

89

2

Foglio1

0123> 3

n. drugs in previous regimen0041892

Grafico1

RAL

TDF

FTC

3TC

DRV/r

RPV

ATV/r

ABC

ETV

EFV

NVP

MVC

AZT

ATV400

LPV/r

ELV/c

n. subjects taking each drug

52

47

46

35

33

29

26

23

21

11

11

6

6

6

4

4

Foglio1


RAL52

TDF47

FTC46

3TC35

DRV/r33

RPV29

ATV/r26

ABC23

ETV21

EFV11

NVP11

MVC6

AZT6

ATV4006

LPV/r4

ELV/c4

n. p

atie

ntsp

er d

rug

clas

saffe

cted

Complexity of drug resistance at baseline

0

10

20

30

40

50

60

70

80

n. drug classes affected by resistance

75

16

27

14

0

0 1 2 3 > 3

56.8% no resistance mutations12.1 % 1 class20.5% 2 classes10.6% 3 classes

Grafico1

n. drug classes affected by resistancen. drug classes affected by resistancen. drug classes affected by resistancen. drug classes affected by resistancen. drug classes affected by resistance

0

1

2

3

> 3

75

16

27

14

0

Foglio1

0123> 3

n. drug classes affected by resistance751627140

0 10 20 30

93908988848277747371706963626058464536353330242016151310

0 1 2

213

148

140

127

124

123

74

72

54

Frequency of single baseline mutations

n. of patients per each mutations

Reverse transcriptase Protease Integrase

0 10 20 30

227225221219218215210208190184181179151118115108103101100

98907574706967654441

54.5% no RT mutations55.3% no PR mutations1 had full INSTI resistance

NNRTI

NRTI

Grafico1

93

90

89

88

84

82

77

74

73

71

70

69

63

62

60

58

46

45

36

35

33

30

24

20

16

15

13

10


3

10

3

3

3

4

9

3

1

11

1

4

28

3

3

1

5

1

19

3

2

5

1

8

2

1

11

20

Foglio1


933

9010

893

883

843

824

779

743

731

7111

701

694

6328

623

603

581

465

451

3619

353

332

305

241

208

162

151

1311

1020

Grafico1

213

148

140

127

124

123

74

72

54


1

1

1

2

1

1

1

1

1

Foglio1


2131

1481

1401

1272

1241

1231

741

721

541

Grafico1

227

225

221

219

218

215

210

208

190

184

181

179

151

118

115

108

103

101

100

98

90

75

74

70

69

67

65

44

41


1

3

2

6

1

21

7

4

1

27

3

1

2

5

1

2

9

1

2

1

1

1

1

8

3

9

3

3

19

Foglio1


2271

2253

2212

2196

2181

21521

2107

2084

1901

18427

1813

1791

1512

1185

1151

1082

1039

1011

1002

981

901

751

741

708

693

679

653

443

4119

Results

• One subject discontinued study drugs at week 24 for headache, one for drug interaction and one died after week 24 of illicit drug abuse.

Trend of HIV-RNA over follow-up, 24 weeksOverall study population (n = 132) by HIV-1 RNA, copies/mL, at week 24

5,98

1,751,74

1,69

5,09

1,71

4,17

0

1

2

3

4

5

6

7

Baseline week 4 week 24

HIV-1 RNA decay in the subpopulation with measurable viral load, log10 copies/mL (n=16)

114 112

Max Min Median

114 HIV

-1 R

NA,

log 1

0co

pies

/mL16

By week 24: subjects with HIV-RNA > 50 copie/mL declined from 12.1% at baseline to 0.8%; subjects in whom no virus was detected (NVD) increased from 67.4% at baseline to 84.4%.

89

16

3 1

Grafico1

BaselineBaselineBaseline

week 4week 4week 4

week 24week 24week 24

Max

Mediana

Min

5.98

1.74

5.09

1.75

1.69

1.71

4.17

4.17

4.17

Foglio1

MaxMedianaMin

Baseline5.981.745.09

week 41.751.691.71

week 244.174.174.17

Grafico1

baselinebaselinebaseline

w 4w 4w 4

w 24w 24w 24

114

112

27

15

19

NVD

1-49

> 50

89

27

16

114

15

3

112

19

1

TivEdO

TivEdO

Sesso:M: 70, F: 42

Età:

media51.8

mediana53

range29 - 77

DS9.7

Rischio:

TD29.5%39

Het33.3%44

MSM35.6%47

Vert0.8%1

Trasf0.8%1

Switch da (sett)

media30.5

mediana29

range24 - 71

DS10.5

Motivi switch











LLV3.8%5

Aderenza2.3%3

Fallimento0.8%1

Terapia pre-


a 2 farmaci31.1%41TDF35.6%47

a 3 farmaci67.3%89FTC34.8%46



31.1%412NA+NNRPV22.0%29

18.2%242NA+PIATV/r19.7%26

> 3 farmaci1.6%2ABC17.4%23

ETV15.9%21

EFV8.3%11

NVP8.3%11

MVC4.5%6

AZT4.5%6

ATV4004.5%6

LPV/r3.1%4

ELV/c3.1%4


RAMs basali


a una classe12.1%162270.8%1932.3%32130.8%1

a 2 classi20.5%272252.3%3907.6%101480.8%1

a 3 classi10.6%142211.6%2892.3%31400.8%1

a > 3 classi0.0%02194.5%6882.3%31271.6%2

2180.8%1842.3%31240.8%1

21515.9%21823.1%41230.8%1

2105.3%7776.8%9740.8%1

2083.1%4742.3%3720.8%1

1900.8%1730.8%1540.8%1

18420.5%27718.3%11

1812.3%3700.8%1

1790.8%1693.1%4

1511.6%26321.3%28

1183.8%5622.3%3

1150.8%1602.3%3

1081.6%2580.8%1

1036.8%9463.8%5

1010.8%1450.8%1

1001.6%23614.4%19

980.8%1352.3%3

900.8%1331.6%2

750.8%1303.8%5

740.8%1240.8%1

706.1%8206.1%8

692.3%3161.6%2

676.8%9150.8%1

652.3%3138.3%11

442.3%31015.1%20

4114.4%19


media32.3%722media32.9%741


range7,6% - 64,2%69 - 2615range6,3% - 57,1%100 - 2338

DS9.7%421DS9.3%445





DS9.1%456DS8.7%462DS9.2%449


NVD54.9%89NVD86.4%114NVD84.8%112

< 50 D20.5%27< 50 D11.4%15< 50 D14.4%19

> 5012.1%16> 502.3%3> 500.8%1




DS3.21DS0.04DS


NVD54.5%24NVD77.3%34NVD84.1%37NVD88.6%39

< 50 D31.8%14< 50 D18.2%8< 50 D13.6%6< 50 D9.1%4

> 5013.6%6> 504.5%2> 502.3%1> 502.3%1




DS1.98DS0.02DSDS





DS0.24DS0.26DS5.86DS2.25


138Q1

181C1

Tivista

Tivista

Sesso:M: 83, F: 30

Età:

media51.4

mediana51

range24 - 82

DS8.59

Rischio:

TD28.3%32

Het23.9%27

MSM46.0%52

Vert1.6%2

Switch da (sett)

media47

mediana44

range24 - 234

DS83.5

Motivi switch







5.9%1diabete0.9%

5.9%1rialzo CPK0.9%


LLV5.3%6

Aderenza3.5%4

Progressione2.6%3

Fallimento27.4%31

Terapia pre-

da TI1.8%2


a 2 farmaci37.2%42RAL48.7%55

a 3 farmaci54.0%61TDF37.2%42


8.2%52NA+INSTI3TC27.4%31

18.0%112NA+NNABC22.1%25

45.9%282NA+PIETV18.6%21

ATV/r16.8%19

> 3 farmaci6.2%7MVC15.0%17

RPV14.1%16

LPV/r7.1%8

EFV6.2%7

ATV4001.8%2

ddI1.8%2

DTG0.9%1


RAMs basali


a una classe8.8%102310.9%19313.3%151560.9%1

a 2 classi22.1%252300.9%19041.6%471555.3%6

a 3 classi50.4%572280.9%18814.2%161540.9%1

a > 3 classi8.0%92270.9%1851.8%21510.9%1

2254.4%58434.5%391480.9%1

2212.6%38232.7%371430.9%1

21923.0%267732.7%371400.9%1

21552.2%59743.5%41350.9%1

21030.0%34737.1%81271.8%2

2085.3%67136.3%41

1930.9%1695.3%6

19010.6%126347.8%54

1884.4%56210.6%12

18444.2%50606.2%7

18119.5%22580.9%1

1797.1%8564.4%5

1514.4%55429.2%33

1385.3%6535.3%6

11810.6%12489.7%11

1162.6%34631.9%36

1154.4%5431.8%2

10810.6%123637.2%42

1064.4%5339.7%11

10328.3%32308.0%9

10111.5%13242.6%3

10014.2%16193.5%4

9812.4%142031.9%36

909.7%11165.3%6

770.6%2156.2%7

758.8%101319.5%22

7415.9%181048.7%55

7015.0%17

695.3%6

6715.0%17

656.2%7

623.5%4

470.9%1

448.8%10

4138.9%44


media32.3%628media32.9%655


range3,3% - 46,5%17 - 1693range6,9% 46,6%36 - 1652

DS9.5%332DS8.5%347





DS11.3%342DS10.8%367DS8.7%351


NVD37.2%42NVD55.7%63NVD73.4%83

< 50 D20.3%23< 50 D27.4%31< 50 D20.3%23

> 5043.4%49> 5016.8%19> 506.2%7




DS0.82DS0.79DS0.49


NVD37.7%20NVD60.4%32NVD71.7%38NVD83.0%44

< 50 D22.6%12< 50 D26.4%14< 50 D20.7%11< 50 D15.1%8

> 5039.6%21> 5012.5%7> 507.5%4> 501.9%1




DS0.8DS0.63DS0.24DS





DS0.22DS0.21DS19.2DS19.4


Foglio3


NVD54.5%24NVD77.3%34NVD84.1%37NVD88.6%39

< 50 D31.8%14< 50 D18.2%8< 50 D13.6%6< 50 D9.1%4

> 5013.6%6> 504.5%2> 502.3%1> 502.3%1




DS1.98DS0.02DSDS

baselinew 4w 24w 48

NVD24343739

1-4914864

> 506211


NVD54.9%89NVD86.4%114NVD84.8%112

< 50 D20.5%27< 50 D11.4%15< 50 D14.4%19

> 5012.1%16> 502.3%3> 500.8%1




DS3.21DS0.04DS

baselinew 4w 24

NVD89114112

1-49271519

> 501631

Foglio3

1-49

> 50

NVD

1-49

> 50

Trend of HIV-RNA over follow-up, 48 weeksLonger follow-up population (n = 44) by HIV-1 RNA, copies/mL, at week 48

HIV-1 RNA decay in the subpopulation with HIV RNA >50 copies/mL log10 (n = 6)

5,49

1,75

4,17

3,19

1,69

4,174,41

1,71

3

1

1,5

2

2,5

3

3,5

4

4,5

5

5,5

6

Baseline week 4 week 24 week 48

Max Min Median

6

HIV-

1 RN

A, lo

g 10

copi

es/m

L

16

By week 48:subjects with HIV-RNA > 50 copie/mL declined from 13.6 % at baseline to 2.3 %subjects in whom no virus was detected (NVD) increased from 54.6% at baseline to 88.6 %

24 39

14

66

2 1 1

Grafico1

BaselineBaselineBaseline

week 4week 4week 4



Max

Mediana

Min

5.49

3.19

4.41

1.75

1.69

1.71

3

3

3

4.17

4.17

4.17

Foglio1

MaxMedianaMin

Baseline5.493.194.41

week 41.751.691.71

week 24333

week 484.174.174.17

Grafico1

baselinebaselinebaseline

w 4w 4w 4

w 24w 24w 24

w 48w 48w 48

34

37

8

4

NVD

1-49

> 50

24

14

6

34

8

2

37

6

1

39

4

1

TivEdO

TivEdO

Sesso:M: 70, F: 42

Età:

media51.8

mediana53

range29 - 77

DS9.7

Rischio:

TD29.5%39

Het33.3%44

MSM35.6%47

Vert0.8%1

Trasf0.8%1

Switch da (sett)

media30.5

mediana29

range24 - 71

DS10.5

Motivi switch











LLV3.8%5

Aderenza2.3%3

Fallimento0.8%1

Terapia pre-


a 2 farmaci31.1%41TDF35.6%47

a 3 farmaci67.3%89FTC34.8%46



31.1%412NA+NNRPV22.0%29

18.2%242NA+PIATV/r19.7%26

> 3 farmaci1.6%2ABC17.4%23

ETV15.9%21

EFV8.3%11

NVP8.3%11

MVC4.5%6

AZT4.5%6

ATV4004.5%6

LPV/r3.1%4

ELV/c3.1%4


RAMs basali


a una classe12.1%162270.8%1932.3%32130.8%1

a 2 classi20.5%272252.3%3907.6%101480.8%1

a 3 classi10.6%142211.6%2892.3%31400.8%1

a > 3 classi0.0%02194.5%6882.3%31271.6%2

2180.8%1842.3%31240.8%1

21515.9%21823.1%41230.8%1

2105.3%7776.8%9740.8%1

2083.1%4742.3%3720.8%1

1900.8%1730.8%1540.8%1

18420.5%27718.3%11

1812.3%3700.8%1

1790.8%1693.1%4

1511.6%26321.3%28

1183.8%5622.3%3

1150.8%1602.3%3

1081.6%2580.8%1

1036.8%9463.8%5

1010.8%1450.8%1

1001.6%23614.4%19

980.8%1352.3%3

900.8%1331.6%2

750.8%1303.8%5

740.8%1240.8%1

706.1%8206.1%8

692.3%3161.6%2

676.8%9150.8%1

652.3%3138.3%11

442.3%31015.1%20

4114.4%19


media32.3%722media32.9%741


range7,6% - 64,2%69 - 2615range6,3% - 57,1%100 - 2338

DS9.7%421DS9.3%445





DS9.1%456DS8.7%462DS9.2%449


NVD54.9%89NVD86.4%114NVD84.8%112

< 50 D20.5%27< 50 D11.4%15< 50 D14.4%19

> 5012.1%16> 502.3%3> 500.8%1




DS3.21DS0.04DS


NVD54.5%24NVD77.3%34NVD84.1%37NVD88.6%39

< 50 D31.8%14< 50 D18.2%8< 50 D13.6%6< 50 D9.1%4

> 5013.6%6> 504.5%2> 502.3%1> 502.3%1




DS1.98DS0.02DSDS





DS0.24DS0.26DS5.86DS2.25


138Q1

181C1

Tivista

Tivista

Sesso:M: 83, F: 30

Età:

media51.4

mediana51

range24 - 82

DS8.59

Rischio:

TD28.3%32

Het23.9%27

MSM46.0%52

Vert1.6%2

Switch da (sett)

media47

mediana44

range24 - 234

DS83.5

Motivi switch







5.9%1diabete0.9%

5.9%1rialzo CPK0.9%


LLV5.3%6

Aderenza3.5%4

Progressione2.6%3

Fallimento27.4%31

Terapia pre-

da TI1.8%2


a 2 farmaci37.2%42RAL48.7%55

a 3 farmaci54.0%61TDF37.2%42


8.2%52NA+INSTI3TC27.4%31

18.0%112NA+NNABC22.1%25

45.9%282NA+PIETV18.6%21

ATV/r16.8%19

> 3 farmaci6.2%7MVC15.0%17

RPV14.1%16

LPV/r7.1%8

EFV6.2%7

ATV4001.8%2

ddI1.8%2

DTG0.9%1


RAMs basali


a una classe8.8%102310.9%19313.3%151560.9%1

a 2 classi22.1%252300.9%19041.6%471555.3%6

a 3 classi50.4%572280.9%18814.2%161540.9%1

a > 3 classi8.0%92270.9%1851.8%21510.9%1

2254.4%58434.5%391480.9%1

2212.6%38232.7%371430.9%1

21923.0%267732.7%371400.9%1

21552.2%59743.5%41350.9%1

21030.0%34737.1%81271.8%2

2085.3%67136.3%41

1930.9%1695.3%6

19010.6%126347.8%54

1884.4%56210.6%12

18444.2%50606.2%7

18119.5%22580.9%1

1797.1%8564.4%5

1514.4%55429.2%33

1385.3%6535.3%6

11810.6%12489.7%11

1162.6%34631.9%36

1154.4%5431.8%2

10810.6%123637.2%42

1064.4%5339.7%11

10328.3%32308.0%9

10111.5%13242.6%3

10014.2%16193.5%4

9812.4%142031.9%36

909.7%11165.3%6

770.6%2156.2%7

758.8%101319.5%22

7415.9%181048.7%55

7015.0%17

695.3%6

6715.0%17

656.2%7

623.5%4

470.9%1

448.8%10

4138.9%44


media32.3%628media32.9%655


range3,3% - 46,5%17 - 1693range6,9% 46,6%36 - 1652

DS9.5%332DS8.5%347





DS11.3%342DS10.8%367DS8.7%351


NVD37.2%42NVD55.7%63NVD73.4%83

< 50 D20.3%23< 50 D27.4%31< 50 D20.3%23

> 5043.4%49> 5016.8%19> 506.2%7




DS0.82DS0.79DS0.49


NVD37.7%20NVD60.4%32NVD71.7%38NVD83.0%44

< 50 D22.6%12< 50 D26.4%14< 50 D20.7%11< 50 D15.1%8

> 5039.6%21> 5012.5%7> 507.5%4> 501.9%1




DS0.8DS0.63DS0.24DS





DS0.22DS0.21DS19.2DS19.4


Foglio3


NVD54.5%24NVD77.3%34NVD84.1%37NVD88.6%39

< 50 D31.8%14< 50 D18.2%8< 50 D13.6%6< 50 D9.1%4

> 5013.6%6> 504.5%2> 502.3%1> 502.3%1




DS1.98DS0.02DSDS

baselinew 4w 24w 48

NVD24343739

1-4914864

> 506211

Foglio3

NVD

1-49

> 50

Trend of CD4 count over follow-up

baseline w 24

200

400

600

800

1000

1200

Aver

age

CD4

coun

t (SD

) cel

ls/m

L

baseline w 24 w 48

200

400

600

800

1000

1200

Aver

age

CD4

coun

t (SD

) cel

ls/m

L

Δ w24: mean + 8.89, range -499/+654 Δ w48: mean +31.63, range -244/+263

Δ= difference from baseline

Overall study population (n = 132), 24 w Subpopulation (n= 44), 48 w

Trend of creatinine over follow-up

baseline week 240,6

0,7

0,8

0,9

1,0

1,1

1,2

1,3 t-test p

ConclusionsA dual regimen of DTG + RPV proved:

Safe with only one drop-out for toxicity at week 24 for headache.

Effective, 99.2% < 50 copies/mL both in the entire cohort at w 24 and in the week 48 subgroup. The proportion of subjects with any detectable viremia halved.

The subject with full INSTI resistance, is taking DTG twice daily having no other choice due to drug interaction and resistance.

One subject had baseline low-level resistance to rilpivirine, one intermediate and 4 high-level resistance (Stanford median score 50, range 15 – 70), but none failed, all having a 24-week follow-up.

One case of virologic failure, due to missed drug refill, with onset of new RT mutations 138Q and 181C, while the integrase gene was unaffected.

CD4+ T-cells absolute count and proportion increased over time both in the entire cohort and in the week 48 subgroup although not statistically significant

Serum creatinine increase was not clinically significant.

Randomized clinical trials will definitely clear out the potential of this attractive regimen.

Aknowledgment to the Tivedo (Tivicay plus rilpivirineObservational Cohort) Group

Capetti Amedeo. 1 st Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, Milano, Italy

Sterrantino G. Infectious Diseases, ‘‘Careggi’’, Hospital, Firenze, Italy

Cossu MV. 1st Infectious Diseases, ASST Fatebenefratelli-Sacco, Milano, Italy

Orofino G. Infectious Diseases, ‘‘Amedeo di Savoia’’, Hospital, Torino, Italy

Barbarini G. 2nd Infectious Diseases, ‘‘Policlinico San Matteo’’ Hospital, Pavia, Italy

De Socio GV. Diseases Climic, Azienda Ospedaliero-Universitaria di Perugia, Italy

Di Giambenedetto S. 2nd Infectious Diseases, ‘‘Policlinico Universitario Gemelli’’, Roma, Italy

Di Biagio A. . Infectious Diseases Clinic, ‘‘San Martino’’ Hospital, Genova

Celesia BM.. Infectious Diseases Unit, University of Catania, ARNAS Garibaldi, Catania

Rizzardini G. 1st Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, Milano, Italy

Switch to Dolutegravir plus Rilpivirine dual therapy in cART-Experienced Subjects: an Italian cohortBackground�Dianummer 3REASONS TO SWITCHPatients’ baseline disposition towards antiretroviralsDianummer 6Frequency of single baseline mutationsResultsTrend of HIV-RNA over follow-up, 24 weeksTrend of HIV-RNA over follow-up, 48 weeksTrend of CD4 count over follow-upTrend of creatinine over follow-up�ConclusionsAknowledgment to the Tivedo (Tivicay plus rilpivirine Observational Cohort) Group�

Documents

Switch to Dolutegravir plus Rilpivirine dual therapy in ...regist2.virology-education.com/2016/14EU/04_Sterrantino.pdf · Switch to Dolutegravirplus Rilpivirine dual therapy in cART-Experienced