1. ART: The New, The Old and The Ugly

2. Our Current ARVS The Nucleoside/ Nucleotide Reverse Transcriptase Inhibitors (NRTIs/ NtRTIs) The Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs ) The Protease Inhibitors (PIs) Abacavir Emtricitabine Lamivudine Stavudine Tenofovir Zidovudine Efavirenz Nevirapine Atazanavir Darunavir Lopinavir Ritonavir Fixed-drug combinations Combivir, Kivexa, Truvada Triomune, Atripla, Triplavar

3. ARVS REGISTSERED IN SOUTH AFRICA The Nucleoside/ Nucleotide Reverse Transcriptase Inhibitors (NRTIs/ NtRTIs) The Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) The Protease Inhibitors (PIs) Abacavir Didanosine Emtricitabine Lamivudine Stavudine Tenofovir Zidovudine Efavirenz Nevirapine Etravirine Rilpivirine Amprenavir Atazanavir Darunavir Indinavir Lopinavir Ritonavir Saquinavir The Integrase Inhibitors (ISTIs) Raltegravir Fixed-drug combinations Combivir, Kivexa, Truvada Triomune, Atripla, Tripalvar, Complera

4. THE ANTIRETROVIRAL DRUGS The Nucleoside/ Nucleotide Reverse Transcriptase Inhibitors (NRTIs/ NtRTIs) The Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs ) The Protease Inhibitors (PIs) Abacavir Didanosine Emtricitabine Lamivudine Stavudine Tenofovir Zidovudine Efavirenz Nevirapine Etravirine Rilpivirine Amprenavir Atazanavir Darunavir Indinavir Lopinavir Ritonavir Saquinavir Tipranavir The Integrase Inhibitors (ISTIs) Raltegravir Elvitegravir Dolutegravir Fixed-drug combinations Combivir, Kivexa, Truvada Triomune, Atripla, Complera The QUAD

5. Drugs to be covered Etravirine Rilpivirine Raltegravir Elvitegravir Dolutegravir Darunavir/r Maraviroc

6. Etravirine Etravirine (ETV) is a second generation NNRTI that ETV works like other NNRTIs by binding to the catalytic site of the RT enzyme Active against HIV with K103N and Y181C This potency appears to be related to etravirine's flexibility as a molecule Dosage 200mg bd

7. Etravirine (2) Pivotal study DUET 1 and 2 OBR +darunavir/r +etravirine/placebo After 24 weeks, pooled analysis - etravirine study arm achieved an undetectable viral load (58.9% vs 41.1%; p<0.0001). There was also a significantly greater increase in CD4 cell count from baseline in the etravirine arm (86 vs 67 cells/mm3; p<0.006).

8. HIV-infected patients with virologic failure on current HAART regimen, history of ≥ 1 NNRTI RAM, ≥ 3 primary PI mutations, and HIV-1 RNA > 5000 copies/mL (DUET-1: N = 612; DUET-2: N = 591) Placebo + Darunavir/Ritonavir-containing OBR* (DUET-1: n = 308; DUET-2: n = 296) Etravirine 200 mg BID + Darunavir/Ritonavir-containing OBR* (DUET-1: n = 304; DUET-2: n = 295) Week 48 *Investigator-selected OBR included darunavir/ritonavir 600/100 mg twice daily + ≥ 2 NRTIs ± enfuvirtide. Week 24 Summary of Study Design DUET 1 and 2 1. Madruga JV, et al. Lancet. 2007;370:29-38. 2. Lazzarin A, et al. Lancet. 2007;370:39-48.

9. Main Findings Significantly more patients achieved HIV-1 RNA < 50 copies/mL with etravirine vs placebo HIV-1 RNA reduction from baseline greater in etravirine arms than placebo arms Etravirine treatment resulted in greater CD4+ cell count increases from baseline compared with placebo (statistical significance reached in DUET-1 only) Madruga JV, et al. Lancet. 2007;370:29-38. Lazzarin A, et al. Lancet. 2007;370:39-48.

10. 13 RT mutations at eight positions were found to reduce ETV activity – V90I, A98G, L100I, K101E/P, V106I, V179D/F, Y181C/I/V and G190A/S

11. Etravirine

12. FDC NO Single day dosage NO Low side effect profile YES High barrier to resistance ? TB friendly NO Pregnancy friendly UNK

13. Rilpivirine

14. Novel NNRTI Single day dosage Co-formulated with TDF and FTC as Complera

15. Rilpivirine 25 mg QD + TDF/FTC 300/200 mg QD (n = 346) EFV 600 mg QD + TDF/FTC 300/200 mg QD (n = 344) *THRIVE only. † Selected by investigator from ABC/3TC, TDF/FTC, ZDV/3TC. Stratification by BL HIV-1 RNA < 100,000 vs ≥ 100,000 copies/mL, NRTI use* Wk 96 final analysis Wk 48 primary analysis Rilpivirine 25 mg QD + 2 NRTIs † (n = 340) EFV 600 mg QD + 2 NRTIs † (n = 338) ECHO, THRIVE: Rilpivirine vs EFV in Treatment-Naive Patients Randomized, double-blind phase III trials Cohen C, et al. AIDS 2010. Abstract THLBB206. ECHO (N = 690) THRIVE (N = 678) Treatment-naive, HIV-1 RNA ≥ 5000 copies/mL no NNRTI RAMs, susceptible to NRTIs

16. ECHO, THRIVE: Rilpivirine vs EFV in Treatment-Naive Patients HIV-1 RNA < 50 copies/mL (ITT-TLOVR) at Wk 48 *P <.0001 for noninferiority at -12% margin. RilpivirineEFV Cohen C, et al. AIDS 2010. Abstract THLBB206. Graphics used with permission. HIV-1 RNA < 50 copies/mL at Wk 48 by BL VL 40 0 100 20 80 82.3 84.3 60 682686 n = ECHOTHRIVEPooled Patients (%) 82.8 82.9 81.7 85.6 338340344346 -3.6 (-9.8 to +2.5) 6.6 (1.6-11.5) > 100,000 copies/mL 125/ 165 121/ 153 246/ 318 149/ 181 136/ 171 285/ 352 77 81 79 80 76 82 Patients (%) 40 0 100 20 80 60 PooledTHRIVE ECHO ≤100,000 copies/mL 162/ 181 170/ 187 332/ 368 136/ 163 140/ 167 276/ 330 90 83 91 84 90 84 Patients (%) 40 0 100 20 80 60 ECHOTHRIVEPooled

17. ECHO, THRIVE: Treatment Failure, Resistance, and Adverse Events Wk 48 OutcomeRilpivirine (n = 686) Efavirenz (n = 682) VF with resistance data, n6228 No NNRTI or NRTI RAMs,%2943  1 Emergent NNRTI RAM,% 6354  Most frequent NNRTI RAME138KK103N  1 Emergent NRTI RAMs, % 6832  Most frequent NRTI RAMM184IM184V Cohen C, et al. AIDS 2010. Abstract THLBB206. Table used with permission. Treatment Failure in ECHO and THRIVE Adverse Events and Discontinuation Resistance at Virologic Failure 6 0 15 3 12 9 4.8 346 n = VF 9.0 682686 6.7 AE 2.0 682686 Patients (%) Wk 48 Outcome, % Rilpivirine (n = 686) Efavirenz (n = 682) P Value DC for AE38.0005 Most Common AEs of Interest, % Any neurologic AE1738<.0001 Any psychiatric AE1523.0002 Any rash314<.0001 Rilpivirine EFV

18. Rilpivirine FDC YES Single day dosage YES Low side effect profile YES High barrier to resistance NO TB friendly NO Pregnancy friendly UNK

19. Raltegravir Novel mode of action Acts on intergrase as an inhibitor 400mg bd

20. Pommier Y, et al. Nat Rev Drug Discov. 2005;4:236-248. HIV Replication Cycle and Drug Targets a.Entry inhibitors b.Reverse transcriptase inhibitors c.Protease inhibitors d.3′-processing inhibitors e.Strand transfer inhibitors

21. BENCHMRK-1 & -2: Patients With HIV-1 RNA < 50 c/mL at Week 48 02 Patients (%) 60 40 0 Weeks 100 80 20 81216243240484 118 117118 232231 230229232229 118 230 118 231 33% 62%* 31% 65%* n = 0 36% 62%* 34% 60%* 119 118119 230228227230229 224 119 228 119 228 Patients (%) 60 40 100 80 20 02 Weeks 81216243240484 *P <.001 for RAL vs placebo, derived from a logistic regression model adjusted for baseline HIV-1 RNA level (log 10 ), first ENF use in OBR, first DRV use in OBR, active PI in OBR. Placebo + OBR RAL + OBR BENCHMRK-1 [1] BENCHMRK-2 [2] 1. Cooper DA, et al. CROI 2008. Abstract 788. 2. Steigbigel R, et al. CROI 2008. Abstract 789. Adapted with permission of Merck & Co., Inc., Whitehouse Station, New Jersey, USA, Copyright © 2008 Merck & Co., Inc. All Rights Reserved.

22. 281 279 Phase III trial of EFV vs RAL, both with TDF/FTC in tx-naive patients At Wk 156, RAL noninferior to EFV (ITT, NC = F analysis) STARTMRK: Efavirenz vs Raltegravir at 156 Wks in Antiretroviral-Naive Patients  CD4+ count : +332 (RAL) vs +295 (EFV) Lazzarin A, et al. ICAAC 2011. Abstract H2-790. HIV-1 RNA < 50 c/mL by Prespecified BL Characteristic* Subgroup, n/N (%)RALEFV Male Female 172/194 (89) 40/43 (93) 159/188 (85) 33/39 (85) Black White Latino 18/23 (78) 83/94 (88) 50/54 (93) 17/22 (77) 82/90 (91) 42/55 (76) VL ≤ 100K VL > 100K 99/105 (94) 113/132 (86) 93/111 (84) 99/116 (85) CD4 ≤ 50 CD4 > 50 - ≤ 200 CD4 > 200 16/23 (70) 80/89 (90) 116/125 (93) 24/28 (86) 68/84 (81) 100/115 (87) HBV ± HCV No coinfection 11/12 (92) 201/225 (89) 11/13 (85) 181/214 (85) Age ≤ median Age > median 109/124 (88) 103/113 (91) 108/131 (82) 84/96 (88) *Study not powered for statistical significance for these comparisons. 100 80 60 40 20 0 HIV-1 RNA < 50 c/mL (%) 016324860728496108120132144156 Wks RAL EFV Patients at Risk, n 281 282 278 280 281 282 280 281 279 281 281 282 86 82 81 79 75 68 ∆ (95% CI) = +7.3 (-0.2 to +14.7) Noninferiority P <.001 RAL EFV

23. REALMRK: 48-Wk Efficacy of Raltegravir BID in Women, Blacks Multicenter, multinational, open-label, single-arm study to determine efficacy of RAL 400 mg BID (+ investigator-selected ARVs) in women, blacks—populations underrepresented in clinical trials Enrollment goals: 25% women (actual 47%), 50% black (actual 74%) No difference in PK parameters by race or sex; no new RAL safety signals noted Retention 84% throughout study; bolstered by strict selection criteria and retention initiatives Male Female Squires K, et al. ICAAC 2011. Abstract H2-789. Black Nonblack IntolerantFailure 0 20 40 60 80 100 HIV-1 RNA < 50 copies/mL at Wk 48 (%) 71.4 85.7 78.6 71.4 66.0 61.4 63.8 64.0 80.5 71.8 69.4 100 NaivePreviously Treated 10/146/711/145/727/4433/5044/6916/2533/4128/3943/6218/18

24. Multicenter, randomized, open-label phase II trial – Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 24 Antiretroviral-naive pts initiating rifampin- containing therapy* for TB coinfection (N = 154) Raltegravir 400 mg BID + Tenofovir + Lamivudine (n = 51) Raltegravir 800 mg BID + Tenofovir + Lamivudine (n = 51) Efavirenz + Tenofovir + Lamivudine (n = 52) Wk 24 Primary endpoint Wk 48 Raltegravir 400 mg BID + Tenofovir + Lamivudine *Rifampin-containing therapy initiated before ART and consisted of rifampin, isoniazid, pyrazinamide, and ethambutol for 2 mos, followed by rifampin and isoniazid for 4 mos. ANRS REFLATE: EFV- vs RAL-Based ART in HIV/TB-Coinfected Pts Grinsztejn B, et al. AIDS 2012. Abstract THLBB01.

25. Virologic Failure at Wk 24 RAL 400 (n = 51) RAL 800 (n = 51) EFV (n = 51) VL > 50 c/mL, n (%)12 (24)4 (8)15 (29) REFLATE: Virologic Suppression at Wk 24 by ART Regimen Grinsztejn B, et al. AIDS 2012. Abstract THLBB01. Graphic reproduced with permission. RAL 400 mg RAL 800 mg EFV 100 80 60 40 20 0 Pts with VL < 50 c/mL (%) 240248121620 Wks ITT; M = F, D/C = F 78 76 67

26. Raltegravir FDC NO Single day dosage NO Low side effect profile YES High barrier to resistance NO TB friendly MAYBE Pregnancy friendly UNK

27. Elvitegravir Intergrase inhibitors. Requires boosting – ritonavir – Cobicistat Co-formulated with a booster, TDF and FTC QUAD-Stribild

28. Cobicistat: A New Boosting Agent Small molecule with no HIV activity – No concern of drug resistance in pts with suboptimal virologic response Similar  from BL in fasting TC and TGs compared with RTV when boosting same agent [1 ] Inhibitor of CYP3A4; many drug–drug interactions [2,3] Modest, rapid increase in serum Cr due to inhibition of tubular secretion [3 ] – Not associated with any change in actual GFR – Other drugs (including ARVs) have similar effect [4,5] Availability of cobicistat has allowed for development of new coformulated agents and regimens 1. Gallant JE, et al. J Infect Dis. 2013;208:32-39. 2. DHHS Guidelines February 2013. 3. TDF/FTC/EVG/COBI [package insert]. 4. RPV [package insert]. 5. DTG [package insert].

29. Renal Monitoring With Cobicistat 9. TDF/FTC/EVG/COBI [package insert]. 10. DHHS Guidelines February 2013. Wk 4—new baseline against which further changes should be measured Change From BL in Serum Cr (mg/dL; IQR) 0 -0.05 -0.10 0.15 0.10 0.05 0.20 248 12 1624324048 Wks BL *Serum phosphorus should be measured in patients at risk for renal impairment At BL,*  Estimated CrCl  Urine glucose  Urine protein

30. Renal Monitoring With Cobicistat Coformulated drugs containing COBI should not be initiated in pts with estimated CrCl < 70 mL/min – Studies ongoing in pts with CrCl < 70 Interpretation of changes in renal function may be problematic when using coformulations of COBI and TDF TDF/FTC/EVG/COBI should not be used with other nephrotoxic drugs 12. TDF/FTC/EVG/COBI [package insert]. 13. DHHS Guidelines February 2013. Serum Cr* UA Change From BL in Serum Cr (mg/dL; IQR) 0 -0.05 -0.10 0.15 0.10 0.05 0.20 At BL,*  Estimated CrCl  Urine glucose  Urine protein Wk 4—new baseline against which further changes should be measured 248 12 1624324048 Wks BL *Serum phosphorus should be measured in patients at risk for renal impairment

31. Key Drug–Drug Interactions With COBI Antacids Benzodiazepines Beta-blockers Calcium channel blockers Erectile dysfunction drugs Inhaled/injectable corticosteroids MVC OCPs (norgestimate) Rifampin Statins 14. DHHS Adult Guidelines. February 2013

32. Cobicistat—Status in EU and US In July 2013, EMEA approved cobicistat as a PK enhancer of atazanavir 300 mg once daily or darunavir 800 mg once daily as part of a complete ART regimen in adults In US, currently approved only as part of coformulated single-tablet regimen TDF/FTC/EVG/COBI – Approval as single agent pending 15. EMA.europa.eu. Assessment report on cobicistat. 16. FDA.gov. Approval of TDF/FTC/EVG/COBI.

33. Elvitegravir/Cobicistat vs EFV or ATV/RTV + TDF/FTC in Treatment-Naive Patients Randomized, double-blind, active-controlled phase III studies Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48 17. Sax P, et al. Lancet. 2012;379:2439-2448. 18. DeJesus E, et al. Lancet. 2012;379:2429-2438. Treatment naive HIV-1 RNA ≥ 5000 copies/mL Any CD4+ cell count Susceptible to TDF, FTC, and EFV, or ATV eGFR ≥ 70 mL/min Study 102 [17] (N = 700) Study 103 [18] (N = 708) EVG/COBI/TDF/FTC QD (n = 348) EFV/FTC/TDF QD (n = 352) EVG/COBI/TDF/FTC QD (n = 353) ATV/RTV + TDF/FTC QD (n = 355)

34. EVG/COBI/TDF/FTC Noninferior to EFV/TDF/FTC Through Wk 144 19. Sax PE, et al. Lancet. 2012;379:2439-2448. 20. Zolopa A, et al. J Acquir Immune Defic Syndr. 2013;63:96-100. 21. Wohl D, et al. ICAAC 2013. Abstract H-672a. Wk 48 Wk 144 EVG/COBI/TDF/FTC (n = 348) EFV/TDF/FTC (n = 352) 80 75 0 20 40 60 80 100 Subjects (%) 88 84 82 Wk 96 77 6 8 7 10 4 5 5 7 6 7 Wk 48 Wk 144 Wk 96 Wk 48 Wk 144 Wk 96 Virologic Success*Virologic FailureD/c due to AEs 95% CI for Difference Wk 48 [1] Wk 96 [2] Wk 144 [3] -12% 12% 0 Favors EFV Favors EVG/COBI -1.3% 11.1% 4.9% 3.6% 8.8% 2.7% -1.6% -2.9% *HIV-1 RNA < 50 copies/mL as defined by FDA Snapshot algorithm.

35. EVG/COBI/TDF/FTC Noninferior to ATV/RTV + TDF/FTC Through Wk 144 22. De Jesus E, et al. Lancet. 2012;379:2429-2438. 23. Rockstroh J, et al. J Acquir Immune Defic Syndr. 2013;62:483-486. 24. Clumeck N, et al. EACS 2013. Abstract LBPS7/2. ATV/RTV + TDF/FTC (n = 355) 78 75 90 87 Wk 48 Wk 144 0 20 40 60 80 100 Wk 96 Wk 48 Wk 144 Wk 96 Wk 48 Wk 144 Wk 96 Virologic Success*Virologic Failure 83 82 55 4 77 7 8 5 4 6 6 8 -12% 12% 0 Favors ATV/RTV Favors EVG/COBI *HIV-1 RNA < 50 copies/mL as defined by FDA Snapshot algorithm. -3.2% 9.4% 3.1% 2.7% 7.5% 1.1% 6.7% -2.1% -4.5% Wk 48 [22] Wk 96 [23] Wk 144 [24] D/c due to AEs 95% CI for Difference EVG/COBI/TDF/FTC (n = 353) Subjects (%)

36. QUAD FDC YES Single day dosage YES Low side effect profile YES High barrier to resistance YES TB friendly NO Pregnancy friendly UNK

37. Dolutegravir Dolutegravir (DTG) is a newer, potent INSI with low nanomolar activity that is suitable for once-daily, unboosted dosing Furthermore, in vitro, DTG retains activity against most isolates carrying major integrase resistance mutations to RAL and/or EVG

38. Dolutegravir Phase III Trials in Treatment-Naive Patients Randomized, noninferiority phase III studies Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48 ART-naive pts VL ≥ 1000 c/mL (N = 822) DTG 50 mg QD + 2 NRTIs* (n = 411) RAL 400 mg BID + 2 NRTIs* (n = 411) *Investigator-selected NRTI backbone: either TDF/FTC or ABC/3TC. ART-naive pts VL ≥ 1000 c/mL HLA-B*5701 neg CrCl > 50 mL/min (N = 833) DTG 50 mg QD + ABC/3TC QD (n = 414) EFV/TDF/FTC QD (n = 419) SPRING-2 [30] (active controlled, double blind) SINGLE [31] (active controlled, double blind) DTG 50 mg QD + 2 NRTIs* (n = 242) DRV/RTV 800/100 mg QD + 2 NRTIs* (n = 242) ART-naive pts VL ≥ 1000 c/mL (N = 484) FLAMINGO [32] (open label) 30. Raffi F, et al. Lancet. 2013;381:735-743. 31. Walmsley S, et al. N Engl J Med. 2013;369:1807-1818. 32. Feinberg J, et al. ICAAC 2013. Abstract H1464a.. 8886 85 88 81 90 83 VL < 50 at Wk 48 VL < 50: DTG/ABC/3TC

39. Samples from participants meeting Protocol defined Virological failure criteria were sent for resistance testing. No participants on DTG have had emergence of a virus with an INI resistance mutation. One participant receiving DTG 10mg developed virus with the mutation M184M/V in reverse transcriptase. Resistance on SPRING 1

40. No treatment-emergent genotypic resistance that resulted in reduced susceptibility to either DLG or the background regimen was seen in the DLG arm in SINGLE. SINGLE

41. Increase the dose of DLG- poor evidence Category B drug. OF course the ever present TB and pregnancy question

42. DLV/ABC and TDF In treatment-naive HIV-infected patients starting initial ART, dolutegravir (DTG) plus abacavir (ABV)/lamivudine (3TC) maintained superiority over efavirenz (EFV)/tenofovir DF (TDF)/emtricitabine (FTC) at Week 96 – DTG arm associated with higher virologic response rate, primarily due to lower rate of discontinuations related to tolerability – DTG arm associated with more favorable safety profile vs control arm, with lower rates of central nervous system (CNS) events, rash, and liver function test elevations No major treatment-emergent mutations conferring INSTI or NRTI resistance detected through 96 weeks in DTG- treated patients

43. Dolutegravir FDC YES Single day dosage YES Low side effect profile YES High barrier to resistance YEs TB friendly NO Pregnancy friendly UNK

44. Darunavir dosing summary Darunavir/r dosing is determined by treatment experience and presence or absence of darunavir mutations on genotypic lab analysis.

45. Treatment-experienced patients POWER 1 compared the efficacy and safety of four doses of DRV (TMC114) plus 100 mg RTV with investigator-selected control protease inhibitors (CPIs) 63% of the patients were resistant to all commercially available PI. Virologic and immunologic outcomes were significantly better in the DRV/r arms compared to the CPI arm. In the 600 mg DRV twice daily arm, mean CD4 gains were as high as 124 cells at 24 weeks and 53 percent attained an HIV RNA level <50 copies/mL;

46. Treatment-experienced patients POWER 3 DRV/r plus optimized background therapy. No comparator arm was used. Of 324 patients who were treated for 48 weeks, 45 percent achieved HIV RNA reductions to <50 copies/ml.

47. Treatment-experienced patients Treatment-experienced patients with recent genotypic testing demonstrating the absence of darunavir-associated mutations: darunavir (800 mg) once daily plus ritonavir (100 mg) once daily. The relevant darunavir mutations include: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V.

48. Treatment-experienced patients POWER 1 and POWER 2 were randomized, multinational, phase IIB trials, which compared DRV co-administered with low-dose RTV to other PIs in a population of highly treatment-experienced patients

49. Treatment-experienced patients Darunavir-associated mutations on genotype: darunavir (600 mg; given as one tablet) twice daily plus ritonavir (100 mg) twice daily. The relevant darunavir mutations include: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V.

50. Treatment-naïve patients Darunavir (800 mg) once daily plus ritonavir (100 mg) once daily ARTEMIS: randomized, open-label, phase 3 non-inferiority trial compared the safety and efficacy of DRV/r (800/100 mg once daily) with LPV/r in 689 treatment-naive patients

51. Treatment-naïve patients At week 48, DRV/r was found to be non- inferior to LPV/r; viral suppression was achieved in 84 versus 78 percent, respectively. At 96 weeks, significantly more patients in the DRV/r arm achieved viral suppression than in the LPV/r arm (79 versus 71 percent) Both treatments were well tolerated.

52. Darunavir FDC NO Single day dosage MAYBE Low side effect profile YES High barrier to resistance YES TB friendly NO Pregnancy friendly UNK

55. Third line Peer Revivew committee Third line drugs now on tender Centrally procured – Receive motivation – Screen – Add to database – Send to Virtual Committee – Committee recommendation to motivator and CPU – Update database

56. Third line committee 130 patients on the database. 115 have already been reviewed. (5 motivations no GT results) Number of motivations declined 12 Number of patients on third line treatment 98