Long Term Therapeutic Success of Etravirine in Switch and Naive Patients

L.Bull, M.Bower, M.NelsonChelsea and Westminster Hospital,

London

Background:

• 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

1. Gazzard et al, AIDS, Nov 2011.

2. 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 44 VL l>50 copies/m

Median CD4 505cells/mm3 Median CD4 count 300cells/mm3 Range 137-1480 cells/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

12 from NRTIS: peripheral neuropathy, lipoatrophy ,nausea, transaminitis7 from raltegravir : transaminitis, peripheral neuropathy, fatigue, poor sleep, depression3 from nevirapine-nausea, depression, transaminitis2 from rilpivirine: nausea4 unknown

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)

Virological Control

0 (n=345)

6 (n=336)

12 (n=291)

24 (n=231)

36 (n=136)

48 (n=39)

0

50

100

150

200

250

300

350

400

Stopped EtravirineDetectable viral loadUndetectable viral load

Time since switching to Etravirine (months)

Num

ber o

f pati

ents

(N)

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

Virological failure 4 patients2 no resistance demonstrated

1 developed resistance to NRTI: 184V/69A (13V, 63P)

1 developed resistance to Etravirine 181C (63P, 71T, 72V, 77I, 93L)

Chemotherapy 3Hepatitis C Rx 3

Mean Lipid Values Before and After Treatment with Etravirine

Mean Lipid Values Before and After Treatment with Etravirine

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

Before EtrAfter Etr

4.93 4.54 P<0.0001*

1.14 1.09 P=0.03*

3.09 2.79 P=0.0001*

4.68 4.42P=0.002*

1.76 1.48P<0.0001*

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

EfavirenzProtease inhibitorsNevirapineRaltegravirARV 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)

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)

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/mm3 (range 340-493).

0 (n=44)

6 (n=44)

12 (n=36)

24 (n=20)

36 (n=10)

05

101520253035404550

Stopped EtravirineUndetectable viral loadDetectable viral load

Time since switching to etravirine (months)

Num

ber o

f pati

ents

(N)

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) Viraemia (6)

Diarrhoea (2) Chemotherapy (2)

Wishing to take less tablets (1)

Heartburn Hepatitis C (1)

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