INDUCTION/MAINTENANCE
Clinical Case
Dr. Jose R Arribas
@jrarribas
INDUCTION/MAINTENANCE
(more or less)
Dr. Jose R Arribas
@jrarribas
Disclosures
• Speaker’s Bureau: Viiv, Janssen, Abbvie, BMS,
Gilead, MSD
• Board Member/Advisory Panel: Merck, Gilead
Induction-maintenance
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Past Medical History
•
•
•
•
•
Syphillis in 1976
Oral candidiasis in Oct 1994
Surgery for gastric perforation 1998
Recurrent genital herpes
Prior smoker 1995
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Past Medical History
• HIV diagnosed in Oct 1993. Heterosexual. 40
years old
• No hepatitis coinfections
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PRIOR ART
• June 1996: AZT-DDI. CD4 328
• May 1997: AZT-DDC
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INDUCTION-MAINTENANCE
• June 1996: AZT-DDI
• May 1997: AZT-DDC
• Resitance testing 10/2004 while still receiving
AZT-ddC
• Genotype showing?
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QUESTION (AZT-DDI, AZT-DDC)
1. M41L, D67N, K70R, T215F, K219Q
2. K65R, L210W
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QUESTION
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INDUCTION-MAINTENANCE
• June 1996: AZT-DDI
• May 1997: AZT-DDC
• Resitance testing 10/2004 while still receiving
AZT-ddC
• M41L, D67N, K70R, T215F, K219Q
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INDUCTION-MAINTENANCE
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INDUCTION-MAINTENANCE
• June 1996: AZT-DDI
• May 1997: AZT-DDC
• Resitance testing 10/2004 while still receiving
AZT-ddC: M41L, D67N, K70R, T215F, K219Q
• May 2005 with 756 CD4 and VL of 38,000
treatment switched to ....
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QUESTION. MAY 2005 (756 CD4 and VL of 38,000,
M41L, D67N, K70R, T215F, K219Q )
1.
2.
3.
4.
5.
Treatment interruption
TDF monotherapy to mantain decreased fitness
LPV/r + FTC + T-20
LPV/r + FTC + EFV
MORE DRUGS
TDF/FTC + ATV/r
LESS DRUGS
TDF
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INDUCTION-MAINTENANCE
• June 1996: AZT-DDI
• May 1997: AZT-DDC
• Resitance testing 10/2004 while still receiving
AZT-ddC: M41L, D67N, K70R, T215F, K219Q
• May 2005 with 756 CD4 and VL of 38,000
treatment switched to ....
• TDF monotherapy
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IMPACT ON FITNESS (M41L, D67N, K70R, T215F, K219Q)
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IMPACT ON FITNESS (M41L, D67N, K70R, T215F, K219Q)
Deeks 2001. NEJM
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INDUCTION-MAINTENANCE
• Remains on TDF monotherapy from May/2005
until March/2009 when he reached 360 CD4
and a viral load of 8.000
• New genotype showing
1. M41L, D67N, T69N; K70R, T215F, K219Q
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INDUCTION-MAINTENANCE
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INDUCTION-MAINTENANCE
• Remains on TDF monotherapy from May/2005
until March 2009 when he reached 360 CD4
and a viral load of 8,000
• New genotype showing?
• M41L, D67N, T69N; K70R, T215F, K219Q
• Patient switched to.... (INDUCTION REGIMEN)
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QUESTION (360 CD4 and a viral load of 8,000, TDF monotherapy
M41L, D67N, T69N; K70R, T215F, K219Q)
1.
2.
3.
4.
TDF/FTC-ATV/r
FTC-ATV/r-RAL
FTC-DRV/r-ETV
FTC-LPV/r-RAL
LESS DRUGS
MORE DRUGS
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QUESTION (360 CD4 and a viral load of 8,000, TDF monotherapy
M41L, D67N, T69N; K70R, T215F, K219Q)
• M41L, D67N, T69N; K70R, T215F, K219Q
• Patient switched to....
• TDF/FTC-ATV/r
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GARDEL
Viral load <50 copies/mL at weeks 48 and 96 (ITTe)
100%
100
90%
90
Patients with HIV-1 RNA
<50 copies/mL (%)
80%
80
90.3%
88.3%
Week 48
(P=0.171, difference +4.6%
[95% CI: –2.2%, +11.8%])
84.4%
83.7%
70%
70
60%
60
Week 96
(P=0.165, difference +5.91%
[95% CI: –2.3%, 14.1%])
50%
50
40%
40
30%
30
20%
20
DT
10%
10
0%0
BSL
W4
4
W8
8
W12
12
W24
24
W36
36
W48
48
TT
W96
96
Time (weeks)
Cahn P et al. EACS 2015. Abstract PS10/4
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INDUCTION-MAINTENANCE
M41L, D67N, T69N; K70R, T215F, K219Q
Patient switched to....
TDF/FTC-ATV/r
Doing well on TDF/FTC-ATV/r from March/2009 to
September/2009 (CD4 558, VL < 50)
• In September/2009 another doctor sees the
patient and ask why this patient is on TDF if
genotype confers high-level resistance ? (CD4
558, VL < 50)
•
•
•
•
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QUESTION
• 1) New doctor doesn’t even think to change a
regimen prescribed by Dr. Arribas
• 2) New doctor couldn’t care less and changes
regimen.
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INDUCTION-MAINTENANCE
• Regimen switched to FTC-ATV/r
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SALT STUDY
Perez-Molina, Journal of Antimicrobial Chemotherapy,
dkw379. http://doi.org/10.1093/jac/dkw379
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SALT STUDY
Perez-Molina, Journal of Antimicrobial Chemotherapy,
dkw379. http://doi.org/10.1093/jac/dkw379
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INDUCTION-MAINTENANCE
• Regimen switched to FTC-ATV/r
• Patient keeps doing well for 5 years on FTCATV/r
• On 11/2014 (CD4 932, VL < 50) starts
treatment with omeprazol
• Regimen switched to...
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QUESTION (CD4 932, VL < 50M, OMEPRAZOL, FTC-ATV/r)
1. FTC-LPV/r
2. FTC-DRV/r
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OLE
• HIV-1 RNA <50 copies/mL
• On triple therapy with for
at LPV/r + 2 nucleosides*
for at least 6 months
• No resistance to LPV/r or
3TC/FTC
• No positive HBsAg
• Randomization 1:1
LPV/r BID + 3TC QD (DT, dual therapy)
LPV/r BID + 2 NUCS (TT, triple therapy)
0
48 weeks
Primary endpoint
*ABC/3TC, TDF/FTC, TDF/3TC
Arribas JR et al. Lancet Infect Dis 2015;15:785–792
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OLE
Dual therapy
100
90
80
70
60
50
40
30
20
10
0
97,29
97,34
Virologic failure
Triple therapy
90,08
89,83
Blips
87.30
87.60
Virologic failure or any blip
Arribas JR et al. Lancet Infect Dis 2015;15:785–792
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Non-inferiority of dual-therapy with
darunavir/ritonavir plus 3TC vs. triple therapy with
darunavir/ritonavir plus TDF/FTC or ABC/3TC for
maintenance of viral suppression: 48-week results
of the DUAL-GESIDA 8014-RIS-EST45 Trial
DUAL: “DarUnavir And Lamivudine”
Federico Pulido. Esteban Ribera. María Lagarde. Ignacio Pérez-Valero. Jesús Santos. José A.
Iribarren. Antonio Payeras. Pere Domingo. José Sanz. Miguel Cervero. Adrián Curran. Francisco J.
Rodríguez. María J. Téllez . Pablo Ryan. Pilar Barrufet. Hernando Knobel. Antonio Rivero.
Belén Alejos. María Yllescas. José R. Arribas.
DUAL-GESIDA-8014-RIS-EST45 Study Group
Abstract #: O331
QUESTION
1. FTC-LPV/r
2. FTC-DRV/r
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INDUCTION-MAINTENANCE
M41L, D67N, T69N; K70R, T215F, K219Q
Regimen switched to FTC-ATV/r
Patient keeps doing well on FTC-ATV/r
On 11/2014 (CD4 932, VL < 50) starts
treatment with omeprazol
• Regimen switched to..
• FTC-DRV/r
•
•
•
•
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INDUCTION-MAINTENANCE
• M41L, D67N, T69N; K70R, T215F, K219Q
• Patient keeps doing well on FTC-ATV/r
• On 11/2014 (CD4 932, VL < 50) starts
treatment with omeprazol
• Regimen switched to..
• FTC-DRV/r
• Patient doing well until August/2015 (CD4
1029, VL <50)
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INDUCTION-MAINTENANCE
• Patient doing well until August/2015 (CD4 1029, VL
<50)
• Angina. Cath with severe artheriosclerotic disease of 3
main vessels. 3 stents
• Depressive/ansious syndrome. On follow-up by
Psychiatry
• Chronic low back pain
• Bisoprolol, Nigroglicerin patch, Aspirin, Trazodone,
Clonazepam, Gabapentine, Atorvastatin
• LDL 65, HDL 40
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INDUCTION-MAINTENANCE
• 8/2015. Severe cardiovascular disease.
Chronic pain. Polypharmacy.
• Regimen switched to....
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QUESTION (M41L, D67N, T69N; K70R, T215F, K219Q.
On DRVr + FTC)
1.
2.
3.
4.
DTG-RPV
LESS DRUGS
FTC-DTG
TDF/FTC-DTG
MORE DRUGS
FTC-DTG-RPV
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SWORD STUDIES
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INDUCTION-MAINTENANCE
• 8/2015. Severe cardiovascular disease.
Chronic pain. Polypharmacy.
• Regimen switched to....
• TDF/FTC-DTG
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QUESTION
• Would it work (TDF/FTC-DTG)?
1. Yes
2. No
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QUESTION
• Would it work better (TAF/FTC-DTG)?
1. Yes
2. No
VIROLOGIST IN THE ROOM
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QUESTION
• Would it work better (TAF/FTC-DTG)?
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INDUCTION-MAINTENANCE
• August/2015. Severe cardiovascular disease.
Chronic pain. Polypharmacy.
• Regimen switched to....
• TVD-DTG
• October/2016. VL < 50. CD4 720
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INDUCTION-MAINTENANCE
• August/2015. Severe cardiovascular disease.
Chronic pain. Polypharmacy.
• Regimen switched to....
• TVD-DTG
• October/2016. VL < 50. CD4 720
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PADDLE Study: Efficacy
#
SCR
BSL
DAY 4
DAY 7
W.2
W.3
W.4
W.6
W.8
W.12
W.24
W.36
W.48
1
5.584
10.909
383
101
<50
<50
<50
<50
<50
<50
<50
<50
<50
2
8.887
10.233
318
<50
<50
<50
<50
<50
<50
<50
<50
<50
<50
3
67.335
151.569
1.565
1.178
97
53
<50
<50
<50
<50
<50
<50
<50
4
99.291
148.370
3.303
432
178
55
<50
<50
<50
<50
<50
<50
<50
5
34.362
20.544
1.292
570
107
<50
<50
<50
<50
<50
<50
<50
<50
6
16.024
14.499
1.634
162
<50
<50
<50
<50
<50
<50
<50
<50
<50
7
37.604
18.597
819
61
<50
<50
<50
<50
<50
<50
<50
<50
<50
8
25.071
24.368
1.377
Not done
105
<50
<50
<50
<50
<50
<50
<50
<50
9
14.707
10.832
516
202
<50
<50
<50
<50
<50
<50
<50
10
10.679
7.987
318
<50
<50
<50
<50
<50
<50
<50
<50
<50
<50
11
50.089
273.676
68.129
3.880
784
290
288
147
<50
<50
<50
<50
<50
12
13.508
64.103
3.296
135
351
84
67
<50
<50
<50
<50
<50
<50
13
28.093
33.829
26.343
539
61
<50
<50
<50
<50
<50
<50
<50
<50
14
15.348
15.151
791
198
<50
61
64
<50
<50
<50
<50
<50
<50
15
23.185
23.500
4.217
192
<50
<50
<50
Not done
<50
<50
<50
<50
<50
16
11.377
3.910
97
143
<50
<50
<50
<50
<50
<50
<50
<50
<50
17
39.100
25.828
1.970
460
52
<50
<50
<50
<50
<50
<50
<50
<50
18
60.771
73.069
2.174
692
156
<50
<50
<50
<50
<50
<50
<50
<50
19
82.803
106.320
2.902
897
168
76
<50
<50
<50
<50
<50
20
5.190
7.368
147
56
<50
<50
<50
<50
<50
<50
<50
SAE = serious adverse event
PDVF = protocol defined virologic failure
Cahn P, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. FARB0104LB.
SAE
PDVF
<50
<50
GEMINI STUDIES
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QUESTION
• Would you switch to FTC-DTG?
1. Yes
2. No
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