switch to dolutegravir plus rilpivirine dual therapy in...
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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
semplificazione46.0%52
tossicità15.0%17% tossicità% totale
52.9%9osteopenia/porosi8.0%
11.8%2lipodistrofia1.8%
11.8%2alterazioni cardiovascolari1.8%
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
Fallimento pre-82.3%93
RAMs basali
nessuna10.6%12RTProINSTI
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
OverallCD4 T0%/mmcCD4 W24
media32.3%628media32.9%655
mediana26.1%632mediana33.8%667
range3,3% - 46,5%17 - 1693range6,9% 46,6%36 - 1652
DS9.5%332DS8.5%347
Subp W48CD4 T0%/mmcCD4 W24CD4 W48
media31.4%596media31.2%611media31.0%630
mediana25.5%601mediana30.5%622mediana31.2%643
range8% - 43%157 - 1287range9% - 43,4%125 - 1321range11% - 43,7%139 - 1583
DS11.3%342DS10.8%367DS8.7%351
OverallHIV RNA T0HIV RNA W4HIV RNA W24
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
mediana2.9mediana2.32mediana2.4
range1,74 - 5,3range1,72 - 4,55range1,91 - 2,9
DS0.82DS0.79DS0.49
Subp W48HIV RNA T0HIV RNA W4HIV RNA W24HIV RNA W48
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
creatinina T0creatinina W24proteinuria T0proteinuria W24
media0.89media0.89media3.47media3.8
mediana0.9mediana0.89mediana0mediana0
range0,50 - 1,67range0,50 - 1,70range0 - 150range0 - 150
DS0.22DS0.21DS19.2DS19.4
Fallimenti0.8%1RAMS nuove0
Foglio3
tivedo
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
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
n. subjects taking each drug
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
n. subjects taking each drug
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
n. subjects taking each drug
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
n. subjects taking each drug
1
1
1
2
1
1
1
1
1
Foglio1
n. subjects taking each drug
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
n. subjects taking each drug
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
n. subjects taking each drug
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
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
semplificazione46.0%52
tossicità15.0%17% tossicità% totale
52.9%9osteopenia/porosi8.0%
11.8%2lipodistrofia1.8%
11.8%2alterazioni cardiovascolari1.8%
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
Fallimento pre-82.3%93
RAMs basali
nessuna10.6%12RTProINSTI
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
OverallCD4 T0%/mmcCD4 W24
media32.3%628media32.9%655
mediana26.1%632mediana33.8%667
range3,3% - 46,5%17 - 1693range6,9% 46,6%36 - 1652
DS9.5%332DS8.5%347
Subp W48CD4 T0%/mmcCD4 W24CD4 W48
media31.4%596media31.2%611media31.0%630
mediana25.5%601mediana30.5%622mediana31.2%643
range8% - 43%157 - 1287range9% - 43,4%125 - 1321range11% - 43,7%139 - 1583
DS11.3%342DS10.8%367DS8.7%351
OverallHIV RNA T0HIV RNA W4HIV RNA W24
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
mediana2.9mediana2.32mediana2.4
range1,74 - 5,3range1,72 - 4,55range1,91 - 2,9
DS0.82DS0.79DS0.49
Subp W48HIV RNA T0HIV RNA W4HIV RNA W24HIV RNA W48
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
creatinina T0creatinina W24proteinuria T0proteinuria W24
media0.89media0.89media3.47media3.8
mediana0.9mediana0.89mediana0mediana0
range0,50 - 1,67range0,50 - 1,70range0 - 150range0 - 150
DS0.22DS0.21DS19.2DS19.4
Fallimenti0.8%1RAMS nuove0
Foglio3
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
baselinew 4w 24w 48
NVD24343739
1-4914864
> 506211
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
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
week 24week 24week 24
week 48week 48week 48
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
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
semplificazione46.0%52
tossicità15.0%17% tossicità% totale
52.9%9osteopenia/porosi8.0%
11.8%2lipodistrofia1.8%
11.8%2alterazioni cardiovascolari1.8%
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
Fallimento pre-82.3%93
RAMs basali
nessuna10.6%12RTProINSTI
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
OverallCD4 T0%/mmcCD4 W24
media32.3%628media32.9%655
mediana26.1%632mediana33.8%667
range3,3% - 46,5%17 - 1693range6,9% 46,6%36 - 1652
DS9.5%332DS8.5%347
Subp W48CD4 T0%/mmcCD4 W24CD4 W48
media31.4%596media31.2%611media31.0%630
mediana25.5%601mediana30.5%622mediana31.2%643
range8% - 43%157 - 1287range9% - 43,4%125 - 1321range11% - 43,7%139 - 1583
DS11.3%342DS10.8%367DS8.7%351
OverallHIV RNA T0HIV RNA W4HIV RNA W24
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
mediana2.9mediana2.32mediana2.4
range1,74 - 5,3range1,72 - 4,55range1,91 - 2,9
DS0.82DS0.79DS0.49
Subp W48HIV RNA T0HIV RNA W4HIV RNA W24HIV RNA W48
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
creatinina T0creatinina W24proteinuria T0proteinuria W24
media0.89media0.89media3.47media3.8
mediana0.9mediana0.89mediana0mediana0
range0,50 - 1,67range0,50 - 1,70range0 - 150range0 - 150
DS0.22DS0.21DS19.2DS19.4
Fallimenti0.8%1RAMS nuove0
Foglio3
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
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�
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