Transcript Long term therapeutic success of etravirine in switch and

Long Term Therapeutic Success of
Etravirine in Switch and Naive
Patients
L.Bull, M.Bower, M.Nelson
Chelsea and Westminster Hospital, London
Background:
•
•
•
•
•
1.
2.
Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor
(NNRTI)
Effective in naïve and switch in those experiencing toxicity to efavirenz1.2
Low toxicity
Once daily
Potential alternative to other first line third agents
Gazzard et al, AIDS, Nov 2011.
Waters et al, AIDS, Jan 2011
2. Waters et al, AIDS, Jan 2011
Methods:
• Retrospective case review of all individuals receiving
Etravirine with a two nucleos(t)ide backbone
• August 2008 and December 2012
Results
N=389
345 VL<50 copies/ml
Median CD4 505cells/mm3
Range 137-1480 cells/mm3
44 VL l>50 copies/m
Median CD4 count 300cells/mm3
Range 31-701cells/mm3
Median VL 44296 copies/ml
Range 508-1819837 copies/ml
Switch Patients with an Undetectable Viral Load Previous Third Agent N=345
Atripla (61%)
Other EFV (11%)
Protease Inhibitors
(19%)
NRTI's (3%)
Other (5%)
Reasons For Switch
Reasons for switching from Efavirenz regimens Reasons for switching from protease
inhibitors
Central nervous system side effects (246)
Diarrhoea (19)
Wanting to conceive (2)
Weight gain/fat redistribution (14)
Cardiovascular risk (7)
Nausea/bloating (6)
Drug interactions (6)
Fatigue (3)
Patient request (3)
Other (9)
Reasons For Switch
Reasons for switching from Efavirenz regimens Reasons for switching from protease
inhibitors
Central nervous system side effects (246)
Diarrhoea (19)
Wanting to conceive (2)
Weight gain/fat redistribution (14)
Cardiovascular risk (7)
Nausea/bloating (6)
Drug interactions (6)
Fatigue (3)
Patient request (3)
Other (9)
12 from NRTIS: peripheral neuropathy, lipoatrophy ,nausea, transaminitis
7 from raltegravir : transaminitis, peripheral neuropathy, fatigue, poor sleep, depression
3 from nevirapine-nausea, depression, transaminitis
2 from rilpivirine: nausea
4 unknown
Virological Control
Number of patients (N)
400
350
300
250
200
Stopped Etravirine
150
Detectable viral load
100
Undetectable viral load
50
0
0
6
12
24
36 48 (n=39)
(n=345) (n=336) (n=291) (n=231) (n=136)
Time since switching to Etravirine (months)
Virological Control:
Time since switching to ETR
(years)
Proportion of patients
remaining undetectable %
(number of patients)
Median CD4 cells/mm3
(range)
0.5
99 (301/304)
535 (118-1552)
1
96 (263/274)
566 (44-1366)
2
97 (203/210)
505 (61-1540)
3
97 (132/136)
662 (164-1623)
4
100 (36/36)
688 (300-1513)
All patients with detectable viral loads were non compliant
Reasons for Cessation of Etravirine
86 patients stopped Etravirine
Toxicity
76 patients
Drug Interactions 6 patients
2 no resistance demonstrated
resistance to NRTI:
Virological failure 14developed
patients
184V/69A (13V, 63P)
1 developed resistance to Etravirine 181C (63P, 71T, 72V,
77I, 93L)
Mean Lipid Values Before and After Treatment with
Etravirine
Mean Lipid Values Before and After Treatment with
Etravirine
5
4.93 4.54
P<0.0001*
4.68 4.42
P=0.002*
4.5
4
Before Etr
3.09 2.79
P=0.0001*
3.5
After Etr
3
2.5
2
1.5
1.14 1.09
P=0.03*
1.76 1.48
P<0.0001*
1
0.5
Total
HDL
LDL
Triglycerides
Cholesterol cholesterol cholesterol (mmol/l)
(mmol/l)
(mmol/l)
(mmol/l)
Ratio
(LDL:HDL)
Switch with a Detectable Viral Load (>40 copies/ml)
-Previous Third Agent, N=44
Efavirenz
Protease inhibitors
Nevirapine
Raltegravir
ARV naïve
9 patients were naïve to therapy. Of the 35 others, median time on their previous
regimen was 9 months (range 1 month to 9 years)
Reasons Patients had VL>40
• 20 patients were restarting therapy after Rx break
(compliance/ADR/toxicity)
• 13 were switched from efavirenz with decreasing viral load with CNS side
effects
• 9 patients were ARV naïve
• 2 patients switched from PI monotherapy with resistance
Reasons for Switch
Efavirenz (17)
Protease
Inhibitors (15)
CNS s effects (17) Drug interaction (3)
Naïve (9)
Nevirapine (2)
Raltegravir (1)
Pt request (4)
Transaminitis (2)
Compliance (1)
Compliance (3)
Previous mental
health (3)
Pt request (3)
Drug users (2)
Diarrhoea (3)
Resistance (2)
Raised CK (1)
Virological Control
Number of patients (N)
• 27/44 fully suppressed their viral load on etravirine
• Remained suppressed for a median of 1 year (range three months to 3
years).
• Median CD4 count at 6 months was 417cells/mm3 (range 340-493).
50
40
30
Stopped Etravirine
20
Undetectable viral
load
10
Detectable viral load
0
0
6
12
24
36
(n=44) (n=44) (n=36) (n=20) (n=10)
Time since switching to etravirine (months)
Naïve Patients
• All naïve patients suppressed their viral load within 6/12, 3
later stopped etravirine after a mean of 16 months due to:
- Heartburn
- X2 drug interactions (chemotherapy/hepatitis c)
• The other 6 have remained undetectable for median of 2
years (range 6 months to 3 years)
Reasons for Cessation of Etravirine
17 patients switched from etravirine
ADR (7)
Possible Drug
interactions (3)
Pt request (1)
Diarrhoea (2)
Chemotherapy
(2)
Wishing to take
less tablets (1)
Heartburn
Hepatitis C (1)
Viraemia (6)
Nausea (2)
CNS symptoms
Cushingoid
All viraemic patients were non compliant with medication
Virological Failure
Patient
Viral load
at start
Viral load
at finish
Time to
<40 viral
load
Time to
failure/
switch
Compliant
Resistance
test
1
41251
4315
N/A
4/12
No
nil
2
60316
169572
4/12
9/12
No
138K
3
681
10201
N/A
4/12
No
181C
4
242162
315248
N/A
3/12
No
nil
5
11870
14585
12/12
18/12
No
181wt/C
6
2629
35002
N/A
3/12
No
138A, 184I,
219 Wt/e
All patients non compliant, 4 develop ETR mutations
Conclusions
• Etravirine is an alternative switch option in individuals with an
undetectable viral load and intolerant of their current third
agent
• Only one individual switching with an undetectable viral load
developed resistance to ETR over a total follow up of 803
patients years
• Switching to etravirine resulted in improvements in total
cholesterol, LDL and TGs
• Limited data available in individuals naïve to therapy and
further data is required