Θα χορηγούσατε προφυλακτική αγωγή προ της έκθεσης (PrEP) 1.ΝΑΙ 2.ΟΧΙ

ΔΙΑΞΙΦΙΣΜΟΙ Περικλής Παναγόπουλος 1 ος Μονομάχος

PrEP ΝΑΙ ή ΟΧΙ

ΣΥΓΚΡΟΥΣΗ ΣΥΜΦΕΡΟΝΤΩΝ Περικλής Παναγόπουλος Advisory boards / Honoraria / Debrief Meetings / Travel Grands GILEAD, MSD, JANSSEN, ABBVIE, NOVARTIS, BMS

PrEP Άπαξ ημερησίως χορήγηση TDF/FTC 300/200mg Συγκεκριμένες πληθυσμιακές ομάδες που βρίσκονται σε ουσιώδη (substantial) κίνδυνο έκθεσης και μόλυνσης MSM IDU Ετεροφυλόφιλους άνδρες και γυναίκες HIV-discordant couples (προφύλαξη κατά τη διάρκεια προσπάθειας τεκνοποίησης)

PROUD: Pragmatic Open-Label Randomized Trial of Pre-Exposure Prophylaxis Results HIV Incidence Incidence/100 person-years Group Infections, n Follow-up (PY) (90% CI) Immediate 3 239 1.3 (0.4-3.0) Use of post-exposure prophylaxis by arm: Deferred Immediate FTC/TDF: 19 13 subjects (5%); 214 15 prescriptions 8.9 (6.0-12.7) Deferred FTC/TDF: 83 subjects (31%); 174 prescriptions Overall 22 453 4.9 (3.4-6.8) 86% (90% CI: 58%-96%) Risk Reduction; P=0.0002 Number needed to treat=13 (90% CI: 9-25) McCormack S, et al. CROI 2015; Seattle, WA. #22LB 10

IPERGAY: On-Demand PrEP Study Design High-risk, HIVuninfected MSM N=400 Condomless anal sex w ith 2 partners w ithin 6 months egfr > 60 ml/min Double-blind, randomized On-demand FTC/TDF treatment (n=199) All participants received a package of preventative measures: counseling repeated HIV testing screening & treatment for other STIs HBV and HAV vaccination condoms and gel On-demand FTC/TDF placebo (n=201) On-demand regimen constitutes: 2 FTC/TDF or 2 placebo 2-24 hrs prior to sexual intercourse exposure 1 FTC/TDF or placebo 24 hrs and then 48 hrs after first intake Primary endpoint: HIV seroconversion Secondary endpoints: Sexual behavior, safety events, adherence Oct. 2014, the DSMB recommended that the placebo arm be discontinued and patients be offered switching into the treatment arm. Molina J, et al. CROI 2015; Seattle, WA. #23LB 11

IPERGAY: On-Demand PrEP Results: Efficacy* 16 subjects infected PBO=14 (incidence: 6.6/100 PY) FTC/TDF=2 (incidence: 0.94/100 PY) Mean follow-up=13 months Average 16 pills / month Number needed to treated: 18 for 1 year to prevent 1 HIV infection Probability of HIV-1 infection 0,2 0,16 0,12 0,08 0,04 0 Placebo P = 0.002 FTC/TDF Months Placebo, n FTC/TDF, n 201 199 141 140 *mitt Population Log-rank test 74 82 55 58 41 43 86% (95% CI: 40-99, p=0.002) reduction in MSM at high risk of HIV infection who took on-demand PrEP Molina J, et al. CROI 2015; Seattle, WA. #23LB 12

WHO 9/2015

EACS Guidelines 2015 (V 8.0) MSM, transgender Μπορεί να χορηγηθεί σε ετεροφυλόφιλους άνδρες και γυναίκες Όταν ο/η σύντροφος είναι HIV (+) άνευ αντιρετροϊκής αγωγής ΠΡΟΣΟΧΗ: ΟΧΙ 100% ΠΡΟΣΤΑΣΙΑ Απαραίτητος ο έλεγχος προ και κατά τη διάρκεια της PrEP

EACS GUIDELINES (V 8.0) Υπάρχουν κι άλλα σεξουαλικώς μεταδιδούμενα νοσήματα ΠΡΟΣΟΧΗ: ΣΕ HBV ΛΟΙΜΩΞΗ Όχι ΜΟΝΑΔΙΚΟ μέτρο πρόληψης Δοσολογία: TDF/FTC X 1/24ωρο On demand

ΦΟΒΟΙ; Εκτός ελέγχου συνταγογράφηση ΜΕΤΡΟ: Συνταγογράφηση από ειδικό Αντοχή λόγω κατάχρησης του ιδίου σκευάσματος θεραπευτικά και προφυλακτικά; ΜΕΤΡΟ: Αντοχή πολύ χαμηλή Ανεπιθύμητες ενέργειες; ΜΕΤΡΟ: Έρχεται το TAF..

Θα χορηγούσατε προφυλακτική αγωγή προ της έκθεσης (PrEP) 1.ΝΑΙ 2.ΟΧΙ

Πότε θα ξεκινούσατε αντιρετροϊκή αγωγή; 1. CD4<500c/mm³ 2. CD4>500c/mm³

ΕΝΑΡΞΗ > ή < ΑΠΟ 500 CD4;

BMD Subanalysis of START: Immediate vs Deferred ART SMART: International, randomized phase IV study involving 215 sites in 35 countries Serious AIDS and Non-AIDS Events, n Treatment-naive pts with CD4+ count > 500 cells/mm³ (N = 4685) Immediate ART Delayed ART (until CD4+ 350 cells/mm³) 42 96 Study stopped by DSMB following results of interim analysis Overall HR: 0.43 (P<.001) HR for serious AIDS-related events: 0.28 (P <.001) HR for non-aids related events: 0.61 (P =.04) Lundgren JD, et al. N Engl J Med. 2015;373:795-807.

START Substudy: BMD Changes With Immediate vs Deferred ART Over 3 Yrs Substudyincluded 193 pts in early ART arm and 204 pts in deferred ART arm with f/u Greater BMD loss in hip and spine with immediate vs deferred ART Estimated mean difference for hip: -1.5% (95% CI: -2.3% to -0.8%; P<.001) Estimated mean difference for spine: -1.6% (95% CI: -2.2% to -1.0%; P<.001) Osteoporosis incidence similar between arms (P=.27) Change From BL (%) Change From BL (%) 0-1 -2-3 -4-5 Total Hip BMD 0 12 24 36 Total Spine BMD Immediate ART -4 Deferred ART -5 0 12 24 36 Mos From Randomization Hoy JF, et al. EACS 2015. Abstract ADRLH-62. Reproduced with permission. 0-1 -2-3

HCV Antivirals in Development Other HCV Compounds NS5As BMS-824393 ATI-0180 NA-808 PRO 20 FGI 103723 ITX 5061635 PF 487868 IMO-2125 IFN-alpha, Medgenics (Biopump SR) P-1101 IFNs CYT-107 SCY-635 BIT-225 Celgosiv ir ACH 2928 BMS 799952 PPI-48 EDP-239 AZD-729 HDV-IFN (Hepasome) Nelson M. Personal Communication. CF-102 Golotimod (SCV07)sc SPC-3649 BMS-79132 CB-5300 IPH 1101 GI-5005 sr-ifn-alpha (LG Life Sciences) PEG-IL- IFN-alpha-2b-IL ANA773 Miglustat Clemizole RG7348 NIM-811 MK-1220 MK5172 Nov -205 Debio025 Nitazoxanin Taribav irin ITCA-6 IFN-alpha-2b-medtronics Interferon-alpha (buccal lozenge, Amarillo) Belerofon Albuferon Locteron IR Phl Phlla Phllb PhllI Telaprev ir ABT 450 Boceprev ir VCH-222+Telaprev ir G S 9190+G S9256 RG7227+RG7128 SCH 900518 BI-201335 VX-813 MK-7009 TMC435350 AVL-181 IDX-375 VX-985 VBY376 BMS-650032 G S 9256 IDX-320 ITMN-191/R7227 R7128 IDX-184 G S 9190 PF868554 VCH-759 MK3281 AZD2795 ABT-072 ANA598 BI-207127 ABT-333 VCH-222 VCH-916 BI-201335+B120127 BMS-790052+BMS-650032 IDX184+IDX320 Combination Products PSI-7977 IDX-136 and IDX-316 PHX-1766 ACH-1625 BMS ACH-1095 TaigGen Bio PSI-879 PSI-7851 PSI-938 IDX-102 IDX-189 Pls Nuc polymerases Non-nuc polymerases

Evolution of HCV Therapy Pros and Cons of Treating vs Deferring Therapy Once PIs Are Available Treat Protease inhibitors substantially increase chance of SVR Successful treatment may arrest progression of liver disease (including potential for cirrhosis, HCC, etc) Many patients already warehoused awaiting DAAs, but when is the right time to exit the warehouse? Defer Current regimens complex, challenging adverse events Potential for better treatment options in future, eg, better response rates, fewer adverse events, shorter duration Risk of resistance if therapy fails; impact on future options?

Σκέψεις Ούτως ή άλλως ξεκινούσαμε στην πλειοψηφία των υποομάδων των ασθενών με CD4 από 350-500c/mm³ Έρχονται νέα φάρμακα, εξίσου αποτελεσματικά, αλλά και λιγότερο τοξικά Γιατί να μην περιμένουμε λίγο χρόνο ακόμη;

ΕΙΔΗ ΚΟΣΤΟΥΣ Άμεσο ιατρικό κόστος(φάρμακα, νοσήλια, αμοιβές, αποζημιώσεις, ποσοστό ΑΕΠ που ξοδεύεται για την υγεία) Άμεσο μη ιατρικό κόστος(συγγενείς, φαγητό, διαμονή, μετακίνηση, βοηθητικές υπηρεσίες που σχετίζονται με την υγεία) Έμμεσο κόστος(απώλεια ζωής, απώλεια εργατοωρών, μειωμένη παραγωγικότητα από τα μέλη της οικογένειας) Άυλο κόστος(πόνος, δυστυχία, επαγγελματική αίγλη, ποιότητα ζωής)

Long Term Non Progressors ELITE CONTROLLERS

Πότε θα ξεκινούσατε αντιρετροϊκή αγωγή; 1. CD4<500c/mm³ 2. CD4>500c/mm³

Τι STR προτιμάτε για έναρξη; 1. ABC/3TC/DTG 2. TDF/FTC/EVG/c

ΘΕΜΑ ΣΥΖΗΤΗΣΗΣ 3 ος παράγοντας Ραχοκοκκαλιά (backbone) TDF/FTC vs ABC/3TC

2015 Update: EACS Guidelines for Treatment of HIV-Infected Pts in Europe Recommended First-line Regimens INSTI + 2 NRTIs DTG/ABC/3TC DTG + TDF/FTC EVG/COBI/TDF/FTC RAL + TDF/FTC NNRTI + 2 NRTIs RPV/TDF/FTC Boosted PI + 2 NRTIs DRV/RTV + TDF/FTC EACS HIV Guidelines. V 8.0. October 2015.

Comparison of Current International Guidelines for Treatment-Naive Pts Regimen DHHS [1] EACS [2] BHIVA [3] IAS-USA [4] GeSIDA [5] EFV/TDF/FTC RPV/TDF/FTC ATV/RTV + TDF/FTC DRV/RTV + TDF/FTC DTG/ABC/3TC DTG + TDF/FTC EVG/COBI/TDF/FTC RAL + TDF/FTC Preferred/recommended Alternative 1. DHHS Guidelines. April 2015. 2. EACS HIV Guidelines. V 8.0. October 2015. 3. BHIVA Guidelines. 2015. 4. Günthard H, et al. JAMA. 2014;312:410-425. 5. GeSIDA. Enferm Infecc Microbiol Clin. 2013;31:602.e1-e602.

Όγδοο επίπεδο διάρθρωσης Ένατο επίπεδο διάρθρωσηςclick to edit Master text styles A5202 (NCT00118898) Estimated effect of 3TC/ABC versus FTC/TDF backbone on the hazard of virological failure Hazard ratio (95% CI) for 3TC/ABC vs FTC/TDF 1,2 Favours 3TC/ABC Favours FTC/TDF with either ATV + RTV or EFV1 1.46 2.33* 3.72 *Log rank test P<0.001 with ATV + RTV2 1.19 2.22 4.14 with EFV2 1.20 2.46 5.05 0.05 1.0 5.0 Hazard ratio N=797; median (25th, 75th) follow-up = 60 weeks (28, 84) DSMB discontinued the 3TC/ABC arm due to higher virological failure with 3TC/ABC vs FTC/TDF in HIV RNA >100,000 3TC: lamivudine; ABC: abacavir: ATV: atazanavir; EFV: efavirenz; DSMB: Data Safety Monitoring Board; FTC: emtricitabine; RTV: ritonavir; TDF: tenofovir disoproxil fumarate 1. Sax PE et al. J Infect Dis 2011;204:1191 1201; 2. Daar ES et al. CROI 2010. San Francisco. Oral 59LB 001/IHQ/14-12//1224aa October 2015

Όγδοο επίπεδο διάρθρωσης Ένατο επίπεδο διάρθρωσηςclick to edit Master text styles GSK ASSERT Study (NCT00549198) Virological efficacy at Week 48 (HIV RNA <50 c/ml) 100 90 FTC/TDF + EFV 3TC/ABC + EFV Efficacy difference fa vouring FTC/TDF = 11.6% 95%CI: 2.2 21.1% 100 Patients, % Proportion 80 70 60 50 40 30 95% CI for difference for FTC/TDF 3TC/ABC 71% 59% Patients, % 80 60 40 75 64 68 55 20 2.2 11.6 21.1 20 10 0 25% 0 4 12 24 36 48 Week ClinicalTrials.gov number, NCT00549198. 62/83 75/100 53/97 61/95 A significant difference in efficacy favouring FTC/TDF was observed 0 <100,000 100,000 c/ml Baseline HIV RNA 3TC: lamivudine; ABC: abacavir; EFV: efavirenz; FTC: emtricitabine; TDF: tenofovir disoproxil fumarate Post FA et al. JAIDS 2010;55:49 57 001/IHQ/14-12//1224aa October 2015

Όγδοο επίπεδο διάρθρωσης Ένατο επίπεδο διάρθρωσηςclick to edit Master text styles Dolutegravir: SPRING-2 (Week 96) rate of virological success for DTG with FTC/TDF vs 3TC/ABC overall and in high viral load* Phase 3, double-blind, randomised, non-inferiority study. Once-daily DTG versus twice-daily RAL, Week 96 post hoc analysis in treatment-naïve infected adults Difference in proportions with HIV-1 RNA <50 copies/ml Favours RAL Favours DTG DTG 50 mg OD RAL 400 mg BID Overall 100,000 c/ml >100,000 c/ml 3TC/ABC FTC/TDF 332/411 (81%) 243/297 (82%) 89/114 (78%) 125/169 (74%) 207/242 (86%) 314/411 (76%) 241/295 (82%) 73/116 (63%) 124/164 (76%) 190/247 (77%) 100,000 c/ml; 3TC/ABC 100,000 c/ml; FTC/TDF >100,000 c/ml; 3TC/ABC >100,000 c/ml; FTC/TDF 98/132 (74%) 145/165 (88%) 27/37 (73%) 62/77 (81%) 98/125 (78%) 143/170 (84%) 26/39 (67%) 47/77 (61%) 3TC: lamivudine; ABC: abacavir; DTG: dolutegravir; FTC: emtricitabine; RAL: raltegravir; TDF: tenofovir disoproxil fumarate -20-10 0 10 20 30 40 50 60 70 Difference in proportion (DTG RAL; unadjusted) Error bars indicate 95% CI Raffi F et al. Lancet Infect Dis 2013;13:927 935; Raffi F et al. IAS 2013. Abstract TULBPE17 *post hoc analysis 001/IHQ/14-12//1224aa October 2015

Όγδοο επίπεδο διάρθρωσης Ένατο επίπεδο διάρθρωσηςclick to edit Master text styles Dutch ATHENA HIV cohort Higher rate of virological failure (VF) with 3TC than FTC Time to VF through Week 240 50 VF at Week 48 Virological failure (%) 40 30 20 10 3TC+TDF+NVP FTC+TDF+NVP 3TC+TDF+EFV FTC+TDF+EFV % VF 40 30 FTC 3TC 27 20 11 11 10 4 0 TDF+EFV TDF+NVP Adjusted* OR (95%CI) for VF (3TC vs FTC) 0 TDF+NVP 2.09 (1.25 3.52) P=0.005 0 48 96 144 192 240 Tim e to virological failure (weeks) OR = odds ratio *Adjusted for transmission, origin, treatment hospital, sex, HBV/HCV Use of 3TC was associated with worse virological outcomes versus FTC regardless of NNRTI component More VFs overall and shorter time to VF with 3TC vs FTC Out of those patients failing, 40/44 patients in both groups developed any RAM (3TC group: n=728; FTC group: n=4,012) Lamivudine and emtricitabine may not be interchangeable in recommended first-line cart 3TC: lamivudine; EFV: efavirenz; FTC: emtricitabine; NVP: nevirapine; RAM: resistance-associated mutation; TDF: tenofovir disoproxil fumarate 1. Rokx C. Glasgow 2014. Oral #154; 2. Rokx C et al. Clin Infect Dis 2015;60:143 153 001/IHQ/14-12//1224aa October 2015

D:A:D Study Continued evidence for an association between ABC and MI risk Adjusted* relative rate (RR) for MI in those currently receiving ABC (P<0.001) overall and stratified by calendar period Adjusted relative rate 5 4 3 2 Overall Pre-March 2008 RR: 1.98 (95% CI: 1.72 2.29) RR: 1.97 (95% CI: 1.68 2.33) Post-March 2008 RR: 1.97 (95% CI: 1.43 2.72) Not currently on ABC *Adjusted for causal pathway, including diabetes, lipids, blood pressure, use of antihypertensive drugs or ACE inhibitors, glucose, CVD risk, weight loss/gain and creatinine. All as time-variated covariates Events/PY 600/295,642 425/169,417 175/126,225 Rate (95% CI)/100 PY 0.20 (0.19, 0.22) 0.25 (0.23, 0.28) 0.14 (0.12, 0.16) Currently on ABC Events/PY 341/71,917 247/40,833 94/31,084 Current use of ABC still associated with 98% increase in MI rate, despite channelling bias away from ABC in patients with Rate (95% CI)/100 PY 0.47 (0.42, 0.52) 0.61 (0.53, 0.68) 0.30 (0.24, 0.36) ABC: abacavir moderate/high risk for CVD disease Sabin C et al. CROI 2014. Boston. #747LB 001/IHQ/14-12//1224aa October 2015

Tenofovir Alafenamide (TAF) TAF is a Targeted Prodrug of TFV - Improves Intracellular TFV-DP Delivery & Reduces Circulating TFV Tenofovir (TFV) Gut TFV Plasma Lymphoid Cells Tenofovir disoproxil fumarate (TDF) TDF TAF TDF TFV TAF TAF Cathepsin A TFV Tenofovir alafenamide (TAF) TFV-MP TFV-DP TAF is more stable in plasma compared with TDF.1 Intact TAF transits directly into target cells where it is intracellularly activated to tenofovir disphosphate (TFV-DP).1-3 TAF at an equivalent dose of 25mg (10mg in boosted regimens) has 90% lower circulating plasma TFV levels compared to TDF 300mg.4-6 1. Lee W et. Antimicr Agents Chemo 2005;49(5):1898-1906. 4. Ruane P, et al. J Acquir Immune Defic Syndr 2013; 63:449-5. 2. Birkus G et al. Antimicr Agents Chemo 2007;51(2):543-550. 5. Sax P, et al. JAIDS 2014. 2014 Sep 1;67(1):52-8. 3. Babusis D, et al. Mol Pharm 2013;10(2):459-66. 6. Sax P, et al. CROI 2015. Seattle, WA. #143LB 51 5

Τι STR προτιμάτε για έναρξη; 1. ABC/3TC/DTG 2. TDF/FTC/EVG/c 52

Ασθενής σε PI παραμένει στην αγωγή του ή απλοποιούμε το σχήμα; 1. ΝΑΙ κάνω switch 2. ΟΧΙ παραμένει στον αναστολέα πρωτεάσης

1997 / 9 ο Πανελλήνιο Συνέδριο AIDS Ερώτημα σε κάποια συνεδρία (σημ. μία διαδραστική συνεδρία με τα χειριστήρια κρεμασμένα με τα καλώδια από τις καρέκλες όπου δε λειτούργησε τίποτε) Ασθενής σε διπλή αγωγή (AZT + 3TC) παραμένει στο ίδιο σχήμα ή αλλάζουμε σε τριπλή αντιρετροϊκή αγωγή;

ΖΗΤΟΥΜΕΝΟ: ΣΥΜΜΟΡΦΩΣΗ

Η συμμόρφωση αυξάνεται όσο μειώνεται η συχνότητα Mean (SD) dose-taking adherence (%) 100 80 60 40 20 0 Dose-taking adherence rates 71 79 69 65 Overall QD BID TID QD vs TID: p=0.008 QD vs QID: p<0.001 BID vs QID: p=0.001 51 QID Dose-timing adherence rates * p-values not calculated 74 59 58 40 * 46 Overall QD BID TID QID Adapted from Claxton AJ et al. Clin Ther 2001;23:1296 1310

LifeLink database Partial and complete non-adherence to ART regimens Retrospective analysis of US healthcare claims for commercially insured population (N=4,588) receiving 2 NRTIs plus NNRTI or PI or INSTI-based ART (2009 2011) Percentage of days 20% 10% 22/11/2015 22/11/2015 11% 8% 22/11/2015 22/11/2015 P<0.0001 P<0.0001 22/11/2015 7% 22/11/2015 P<0.0001 22/11/2015 22/11/2015 Partial adherence Complete non-adherence 0% RAL n=522 Boosted PI n=1,601 NNRTI n=657 STR n=1,751 STR patients had significantly more days with a complete regimen RAL: raltegravir 001/IHQ/14-12//1224aa October 2015 Cohen C et al. ICAAC 2012. San Francisco, CA. #H-211

Όγδοο επίπεδο διάρθρωσης Ένατο επίπεδο διάρθρωσηςclick to edit Master text styles STR vs MTR: US analysis of claims database Real-world ART persistence with single-tablet regimens: Stribild vs Eviplera vs Atripla vs multi-tablet regimens (MTRs) Adjusted hazard ratios (ahr) for treatment discontinuation Comparing persistence with STRs vs MTRs STRs vs MTRs STRs vs NNRTI- or INSTI-based MTRs ATR vs MTRs EPA vs MTRs STB vs MTRs Comparing persistence among STRs EPA vs ATR STB vs ATR STB vs EPA Comparing backbone effects on persistence FTC/TDF vs ABC/3TC FTC/TDF + PI+RTV vs ABC/3TC + PI+RTV Favours STR Favours MTR 0.54 (0.50, 0.58) 0.61 (0.54, 0.68) 0.70 (0.57, 0.86) 0.33 (0.22, 0.48) 0.31 (0.23, 0.42) Favours First STR Favours Second STR 0.47 (0.32, 0.69) 0.45 (0.33, 0.60) 0.95 (0.61, 1.48) Favours FTC/TDF Favours ABC/3TC 0.77 (0.64, 0.93) 0.69 (0.54, 0.88) 3TC: lamivudine; ABC: abacavir; ATR: Atripla; EPA: Eviplera; FTC: emtricitabine; RTV: ritonavir; STB: Stribild; TDF: tenofovir disoproxil fumarate 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 STRs are associated with higher persistence when compared to MTR Adjusted HR (95% CI) Stribild and Eviplera were associated with the highest rates of persistence Truvada was associated with higher persistence when compared to ABC/3TC Sweet D et al. Glasgow 2014. #P6 001/IHQ/14-12//1224aa October 2015

ΑΝΑΣΤΟΛΕΙΣ ΙΝΤΕΓΚΡΑΣΗΣ r/lpv - CASTLE 76 r/lpv - ABT 730 77 r/lpv - ARTEMIS 78 EFV - 934 80 EFV - STARTMRK EFV - E CHO/THRIVE EFV - 102 RPV - E CHO/THRIVE r/drv - ARTEMIS 82 82 83 84 84 RAL - STARTMRK 86 r/atv - CASTLE 78 r/atv - 103 87 DTG - SINGLE * DTG - SPRING-2 * STRIBILD - 102 88 88 88 STRIBILD - 103 90 65 70 75 80 85 90 95 Proportion (%) of patie nts <50 copies/ml at 48 weeks (TLOVR)

Όγδοο επίπεδο διάρθρωσης Ένατο επίπεδο διάρθρωσηςclick to edit Master text styles WAVES Virological outcome at Week 48 ATV+RTV ATV: atazanavir; COBI: cobicistat; EVG: elvitegravir; FTC: emtricitabine; RTV: ritonavir; TDF: tenofovir disoproxil fumarate EVG/COBI/FTC/TDF arm demonstrated increased virological success at 48 weeks compared to ATV+RTV+FTC/TDF arm (87 vs 81%, p=0.03) Adjusted difference: 6.5% (95% CI 0.4% to 12.6%) Squires K et al. IAS 2015. Vancouver 001/IHQ/14-12//1224aa October 2015

Αναστολείς πρωτεάσης DRV/r ATV/r LOP/r

STRATEGY-PI (Study 115) Study design Multicentre, randomised, open-label, 96-week study STRATEGY-PI n=293 EVG/COBI/FTC/TDF PI + RTV + FTC/TDF 2:1 HIV-1 RNA <50 c/ml for 6 months 2 prior ARV regimens No resistance to FTC or TDF No history of virological failure egfrcg 70mL/min n=140 PI + RTV + FTC/TDF Week 48 Week 96 Primary endpoint: HIV-1 RNA <50 c/ml at Week 48 by Snapshot (non-inferiority margin of 12%). If non-inferiority is established, then superiority will be tested Secondary endpoint: Safety and tolerability at Weeks 48 and 96 Other endpoints: Patient-reported outcomes* Study GS-US-236-0115 is registered with ClinicalTrials.gov, number NCT01475838 PI + RTV + FTC/TDF: ritonavir-boosted protease inhibitor and emtricitabine/tenofovir DF *HIV-specific, health-related quality of life questionnaires: HIV Symptom Index, HIV Treatment Satisfaction EVG/COBI/FTC/TDF: single-tablet regimen elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, tenofovir DF 300 mg; Stribild COBI: cobicistat; EVG: elvitegravir; FTC: emtricitabine; RTV: ritonavir; TDF: tenofovir disoproxil fumarate Arribas J et al. BHIVA 2015. Brighton, UK #P1 001/IHQ/14-12//1224aa October 2015

1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Όγδοο επίπεδο διάρθρωσης Ένατο επίπεδο διάρθρωσηςclick to edit Master text styles Austrian persistence analysis Lower rate of treatment modification with RPV in ART-naive patients Austrian HIV cohort analysed reasons for change or discontinuation of an initial ART regimen in 965 treatment-naive patients who initiated therapy between 2011 and 2014 DRV (n=282), RAL (n=96), EFV/ATR (n=118), ATV (n=161), RPV/EPA (n=108) and others (n=200) 0 Time to treatment modification by drug group DRV RAL EFV (ATR) ATV RPV (EPA) Other 0 1 2 3 Duration of therapy in years Overall probability of treatment modification at Year 1, 2 and 3 was 29%, 40% and 50%, respectively Availability of more effective or convenient treatment (29%) was the main reason for modification EFV was modified in 53% due to central nervous system toxicity and ATV in 28% for gastrointestinal toxicity including hyperbilirubinemia RPV was found to be a regimen with the lowest modification rate over three years compared to all other regimens studied ATR: Atripla; ATV: atazanavir; DRV: darunavir; EFV: efavirenz; EPA: Eviplera; RAL: raltegravir; RPV: rilpivirine Rappold M et al. Glasgow 2014. #P236 001/IHQ/14-12//1224aa October 2015

Όγδοο επίπεδο διάρθρωσης Ένατο επίπεδο διάρθρωσηςclick to edit Master text styles SPIRIT: Weeks 24 and 48: Virological suppression FDA Snapshot analysis ITT population Snapshot at 24 weeks Snapshot at 48 weeks Proportion of subjects, % 100 90 80 70 60 50 40 30 20 10 0 93.7 89.9 92.1 (HIV-1 RNA <50 c/ml) RPV/FTC/TDF (immediate switch, Day 1 to W24) PI+RTV+2NRTIs (delayed, Day 1 to W24) RPV/FTC/TDF (delayed switch, W24 to W48) Switching to RPV/FTC/TDF was non-inferior to remaining on PI+RTV+2NRTIs for 24 weeks difference 3.8, CI [ 1.6, 9.1] 0.9 5.0 5.4 5.0 1.3 297/317143/159140/152 3/317 8/159 2/152 17/3178/159 10/152 0 Virological suppression Virological failure No data 6.6 12 10 8 6 4 2 Virological suppression RPV/FTC/TDF (immediate switch, Day 1 to W48) 283/317 8/317 26/317 Virological failure Similar rates of virological suppression were seen at 48 weeks of RPV/FTC/TDF No data FTC: emtricitabine; RPV: rilpivirine; RTV: ritonavir; TDF: tenofovir disoproxil fumarate Palella FJ et al. AIDS 2014;28(3):335 344 001/IHQ/14-12//1224aa October 2015

Όγδοο επίπεδο διάρθρωσης Ένατο EPA in επίπεδο switch (Italy) διάρθρωσηςclick to edit Master text styles Switching to EPA in virologically suppressed patients improves lipid profile Retrospective, multicentre, cohort study switching from PI or NNRTI (n=508) At 6 months, 1.1% VF and 5.5% had discontinued for any reason Only the number of pre-switch regimens was associated with VF (HR 1.13, p=0.001) Type of pre-switch regimen was not associated with discontinuation or failure; with no VFs observed with switching off ATR or RAL regimens Total cholesterol Triglycerides Switching to EPA in virologically suppressed patients could be a good strategy with low risk of virological failure or treatment discontinuation with significant improvement in lipid profile. ATR: Atripla; EPA: Eviplera; RAL: raltegravir Pinnetti C et al. Glasgow 2014. #P280 001/IHQ/14-12//1224aa October 2015

Όγδοο επίπεδο διάρθρωσης Ένατο επίπεδο διάρθρωσηςclick to edit Master text styles PRO-STR Spanish STR Cohort Switching to Eviplera due to regimen intolerance Presence of symptoms based on ACTG Symptom Index Prospective, multicentre study of HIV-infected patients on stable ART for 3 months who switched to EPA from NNRTI (75%) and PI (25%) due to intolerance of previous regimen (n=122) * = p value <0.05 for paired data vs baseline X = p value 0.001 for paired data vs baseline Baseline Week 4 Week 16 In patients with intolerance to their previous cart, switching to a single-tablet regimen of EPA resulted in significant improvements of symptomatology (as measured by ACTG Symptom Index) Podzamczer D et al. Glasgow 2014. #282 ACTG: AIDS Clinical Trial Group; EPA: Eviplera 001/IHQ/14-12//1224aa October 2015

Αλλάζουμε λοιπόν έστω και με καθυστέρηση...

Ασθενής σε PI παραμένει στην αγωγή του ή απλοποιούμε το σχήμα; 1. ΝΑΙ κάνω switch 2. ΟΧΙ παραμένει στον αναστολέα πρωτεάσης