Miss Jane Rowlands. Chelsea and Westminster Hospital, London THIRD JOINT CONFERENCE OF BHIVA AND BASHH 2014

Transcription

1

2 THIRD JOINT CONFERENCE OF BHIVA AND BASHH 2014 Miss Jane Rowlands Chelsea and Westminster Hospital, London 1-4 April 2014, Arena and Convention Centre Liverpool

3 Multi-centre open-label study of switching from Atripla to Eviplera for CNS toxicity Jane Rowlands Senior Research Nurse Chelsea and Westminster Hospital

4 Background Current guidelines recommend Efavirenz (EFV) based regimens for 1 st line treatment. (1) EFV based CNS toxicity common - leading factor for switch. (2) Eviplera (TFV/FTC/RPV) is an alternative with lower incidence of CNS toxicities. (3) Proved non-inferior to EFV in naïve patients with VL <100,000 copies/ml. (3) 1.British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012 HIV Medicine (2014) Waters L et al. AIDS 2011;25: Cohen et al. AIDS 2013; 27 (6)

5 Primary Objective Whether switching individuals with CNS intolerance from Atripla to Eviplera is associated with resolution of toxicity after 12 weeks. Efavirenz SPC based Questionnaire DAIDS Adverse Event Grading Scores converted to % Low score = low CNS toxicity

6 Secondary Objectives CNS toxicity after 24 weeks Sleep Scores CD4 & Viral Load Cholesterol & Triglycerides Anxiety & Depression Neurocognitive Functioning EFV & RPV PK

7 Study Design Multi-centre, open-label study of 24 weeks. All patients included were fully supressed on Atripla and were experiencing CNS toxicity after at least 12 weeks of therapy. All patients were switched to EPA at baseline.

8 Methodology Baseline Week 1 Week 2 SQ, CNS Toxicity, HADS, Cogstate, PK sample PK sample only PK sample only Week 4 Week 12 Week 24 SQ, CNS Toxicity, Cogstate, PK sample SQ, CNS Toxicity, HADS, PK sample SQ, CNS Toxicity, HADS, Cogstate, PK sample

9 Questionnaire scoring CNS toxicity questionnaire 10 items based on EFV SPC DAIDS grading system Converted to % of 100 Low score = low CNS toxicity Sum total of all grades of CNS toxicity Example: Grade 1 dizziness Grade 2 headache Grade 2 depression Grade 1 insomnia = CNS Score 6 HADS 14 items: 7 anxiety, 7 depression Converted to % of 100 Low score ( 7/21 for A or D): unlikely A or D Sleep questionnaire 19 standardised items Converted to % of 100 Low score = better quality sleep

10 Results 40 patients enrolled 4 sites 36 male and 4 female Mean age 47 (range: 24-73) years Median time on EFV 42 months (range: 24 to 100) Median CD4 at baseline 610 cells/µl No significant non-cns AE s

11 Primary Objective: Does switching to EPA resolve CNS toxicity after 12 weeks? Baseline Week 4 Week Total CNS Score Median Total CNS Score

12 Primary Objective: Does switching to EPA resolve CNS toxicity after 12 weeks? 120 Proportion of patients (%) reporting symptoms Baseline Week 4 Week 12

13 Primary Objective: Does switching to EPA resolve CNS toxicity after 12 weeks? Proportion of patients (%) reporting symptoms P=0.034 P=0.021 P=0.005 P=0.029 P=0.008 P=0.001 P=0.008 P= Baseline Week 4 Week 12

14 Secondary Objective: Does Switching to EPA resolve CNS toxicity after 24 weeks? Proportion of patients (%) reporting symptoms P=0.103 P=0.020 P=0.021 P=0.012 P=0.004 P=0.999 P=0.001 Baseline Week 4 Week 12 Week 24

15 Median Sleep Scores (%) Secondary Objective: Does switching to EPA improve sleep scores over 24 weeks? Baseline Week 4 Week 12 Week 24 Time point

16 HADS Score (%) Secondary Objective : Does switching to EPA have an impact on anxiety and depression scores? P=0.001 Baseline Week 12 Week 24 Overall HADS Score HAD Anxiety Score HAD Depression score

17 CD4 cells/mm3 Secondary Objective: Does Switching to EPA impact on CD4 and Viral load? P= Baseline Week 12 Week 24 Change in CD4 (median) CD4 CD4 All patients remained virologically supressed throughout 24 weeks.

18 Lipid concentration Mmol/L Secondary Objective : Does switching to EPA have an impact on lipids? Baseline Week 4 Week 12 Week 24 Total Cholesterol HDL Cholesterol LDL Cholsterol Triglycerides Total Cholesterol HDL Cholesterol LDL Cholsterol Triglycerides

19 Drug concentration (ng/ml) Secondary Objective: What is the impact on rilpivirine plasma concentrations following switch? GEOMETRIC MEAN RILPIVIRINE GEOMETRIC MEAN EFAVIRENZ Time (weeks)

20 Conclusions Switching ATR to EPA results in significant improvement of CNS AEs. Virologic suppression is maintained. Important to identify patients with CNS toxicity as switching to alternative agents may result in improved toxicity profiles and therefore tolerability of cart.

21 Acknowledgements Subject volunteers for participating SSAT and Gilead Co-Authors: Chris Higgs (1), Marta Boffito (1), Manisha Yapa (1), Nahum De Esteban (2), Siobhan McKenna (4), Nicky Perry (3), Alan Winston (4), Laura Waters (2), Martin Fisher (3) & Mark Nelson (1, 4). 1. Chelsea and Westminster Hospital, London. 2. Mortimer Market clinic, London. 3. Brighton and Sussex University Hospitals. 4. Imperial College School of Medicine, London.

22