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Long Term Therapeutic Success of Etravirine in Switch and Naive Patients L.Bull, M.Bower, M.Nelson Chelsea and Westminster Hospital, London.

Published byGregory Lyons Modified over 8 years ago

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Presentation on theme: "Long Term Therapeutic Success of Etravirine in Switch and Naive Patients L.Bull, M.Bower, M.Nelson Chelsea and Westminster Hospital, London."— Presentation transcript:

1 Long Term Therapeutic Success of Etravirine in Switch and Naive Patients L.Bull, M.Bower, M.Nelson Chelsea and Westminster Hospital, London

2 Background: Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) Effective in naïve and switch in those experiencing toxicity to efavirenz 1.2 Low toxicity Once daily Potential alternative to other first line third agents 1. Gazzard et al, AIDS, Nov 2011. 2. Waters et al, AIDS, Jan 2011

3 Methods: Retrospective case review of all individuals receiving Etravirine with a two nucleos(t)ide backbone August 2008 and December 2012

4 Results N=389 345 VL 50 copies/m Median CD4 505cells/mm 3 Median CD4 count 300cells/mm 3 Range 137-1480 cells/mm 3 Range 31-701cells/mm 3 Median VL 44296 copies/ml Range 508-1819837 copies/ml

5 Switch Patients with an Undetectable Viral Load - Previous Third Agent N=345

6 Reasons For Switch Reasons for switching from Efavirenz regimensReasons 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)

7 Reasons For Switch 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 Reasons for switching from Efavirenz regimensReasons 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)

8 Virological Control

9 Virological Control: Time since switching to ETR (years) Proportion of patients remaining undetectable % (number of patients) Median CD4 cells/mm 3 (range) 0.599 (301/304)535 (118-1552) 196 (263/274)566 (44-1366) 297 (203/210)505 (61-1540) 397 (132/136)662 (164-1623) 4100 (36/36)688 (300-1513) All patients with detectable viral loads were non compliant

10 Reasons for Cessation of Etravirine 86 patients stopped Etravirine Toxicity 76 patients Drug Interactions 6 patients Virological failure 4 patients 2 no resistance demonstrated 1 developed resistance to NRTI: 184V/69A (13V, 63P) 1 developed resistance to Etravirine 181C (63P, 71T, 72V, 77I, 93L)

11 Mean Lipid Values Before and After Treatment with Etravirine

12 4.93 4.54 P<0.0001* 1.14 1.09 P=0.03* 3.09 2.79 P=0.0001* 4.68 4.42 P=0.002* 1.76 1.48 P<0.0001*

13 Switch with a Detectable Viral Load (>40 copies/ml) -Previous Third Agent, N=44 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)

14 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

15 Reasons for Switch Efavirenz (17)Protease Inhibitors (15) Naïve (9)Nevirapine (2)Raltegravir (1) CNS s effects (17)Drug interaction (3)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)

16 Virological Control 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/mm 3 (range 340-493).

17 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)

18 Reasons for Cessation of Etravirine 17 patients switched from etravirine ADR (7)Possible Drug interactions (3) Pt request (1)Viraemia (6) Diarrhoea (2)Chemotherapy (2) Wishing to take less tablets (1) HeartburnHepatitis C (1) Nausea (2) CNS symptoms Cushingoid All viraemic patients were non compliant with medication

19 Virological Failure PatientViral load at start Viral load at finish Time to <40 viral load Time to failure/ switch CompliantResistance test 1412514315N/A4/12Nonil 2603161695724/129/12No138K 368110201N/A4/12No181C 4242162315248N/A3/12Nonil 5118701458512/1218/12No181wt/C 6262935002N/A3/12No138A, 184I, 219 Wt/e All patients non compliant, 4 develop ETR mutations

20 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

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