Résumé IAS 2015 Benoit Trottier, md Professeur agrégé de clinique, université de Montréal Chef, Service de consultation-Liaison VIH/SIDA, CHUM Directeur.

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1 Résumé IAS 2015 Benoit Trottier, md Professeur agrégé de clinique, université de Montréal Chef, Service de consultation-Liaison VIH/SIDA, CHUM Directeur de la recherche, clinique médicale L’actuel

2 Conflits d’intérêts potentiels? BENOIT TROTTIER A ÉTÉ, AU COURS DES 2 DERNIÈRES ANNÉES, CONSULTANT/CONFÉRENCIER POUR: ABBVIE, BMS, GILEAD, MERCK, JANSSEN, VIIV HEALTHCARE PAS DE SUPPORT $ POUR VANCOUVER 2

3 Au menu  Épidémiologie  Prévention  Nouveautés en traitement ARV  Complications de l’infection VIH et des traitements  Co-infection

4 Au menu  Épidémiologie  Prévention  Nouveautés en traitement ARV  Complications de l’infection VIH et des traitements  Co-infection

5 clinicaloptions.com/hiv Highlights of IAS 2015 UNAIDS: 90-90-90 Treatment Targets Levi J, et al. IAS 2015. Abstract MOAD0102. Reproduced with permission. 100 80 60 40 20 0 HIV Positive People DiagnosedOn ARTViral Suppression 36.9 million 33.2 million 29.5 million 26.9 million Target 1: 90% of HIV+ people diagnosed Target 2: 90% of diagnosed people on ART Target 3: 90% of people on ART with HIV-1 RNA suppression 90% 81% 73% People (%)

6 clinicaloptions.com/hiv Highlights of IAS 2015 UNAIDS: 90-90-90 Global Estimated Gaps 100 80 60 40 20 0 HIV Positive People DiagnosedOn ARTViral Suppression* 36.9 million 19.8 million 15.0 million 11.6 million Breakpoint 1: 13.4 million undiagnosed Breakpoint 2: 14.9 million not treated Breakpoint 3: 15.3 million not virally suppressed 53% 41% 32% Levi J, et al. IAS 2015. Abstract MOAD0102. Reproduced with permission. *HIV-1 RNA < 1000 copies/mL. People (%)

7 Proportions PVVIH dans le monde From slide G Pialoux; Sources : OMS et Anrs/sneg 15-20 % (17,8 %) Montréal:13.6-15

8 Au menu  Épidémiologie  Prévention  Nouveautés en traitement ARV  Complications de l’infection VIH et des traitements  Co-infection

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10 Les modes de prévention du VIH ANNEES TasP Traitement des MST Positive Prevention & Testing Infectés ANNEES Non exposés Comportemental, Structurel HEURES (Vaccins) ART PrEP Microbicides Exposés ( precoital/coital) 72h PEP Exposés (postcoital) Selon Cohen, IAS 2008 Circoncision, Condom etc

11 Message de prévention en Argentine 11

12 clinicaloptions.com/hiv Highlights of IAS 2015 HPTN 052: ART for Prevention of HIV Transmission in Serodiscordant Couples  International, randomized, controlled trial Stable, healthy, sexually active, HIV-discordant couples with 350-550 CD4+ cells/mm 3 (N = 1763 couples) Early ART Arm Initiate ART immediately (n = 886 couples) Delayed ART Arm Initiate ART at CD4+ cell count ≤ 250 cells/mm 3 or at development of AIDS-defining illness (n = 877 couples)  Participants informed of interim results beginning May 2011; ART offered to all index participants in delayed ART arm; study continued until May 2015 to determine durability of HIV transmission prevention  84% of pts in delayed ART arm had initiated ART at Yr 1; 98% of pts had initiated ART prior to study closure Cohen MS, et al. IAS 2015. Abstract MOAC0101LB. Résultats finaux de l’HPTN 052

13 clinicaloptions.com/hiv Highlights of IAS 2015  No linked HIV transmissions observed when index participant stably suppressed on ART HPTN 052: Partner Infections With Early vs Delayed ART  8 linked HIV infections diagnosed after seropositive pt started ART –4 infections likely occurred before, or soon after, ART initiation, and 4 infections occurred after ART failure in seropositive pt  Unlinked partner infection rates similar between study arms Cohen MS, et al. IAS 2015. Abstract MOAC0101LB. April 2005 - May 2011May 2011 - May 2015 Overall (April 2005 - May 2015) Partner Infections, n (rate/100 PY) Early (1751 PY F/U) Delayed (1731 PY F/U) Early (2563 PY F/U) Delayed (2449 PY F/U) Early (4314 PY F/U) Delayed (4180 PY F/U) All4 (0.23)42 (2.43)15 (0.59)17 (0.69)19 (0.44)59 (1.41) Linked1 (0.06)36 (2.08)2 (0.08)7 (0.29)3 (0.07)43 (1.03) Risk Reduction With Early ART, % All infections91--14--69-- Linked infections 97--72--93--

14 clinicaloptions.com/hiv Highlights of IAS 2015 PL-1 Rafael Landovitz, MD

15 clinicaloptions.com/hiv Highlights of IAS 2015  International, randomized, open-label phase II trial; results reported from Harlem and Bangkok cohorts HPTN 067/ADAPT: PrEP for MSM/TGW Mannheimer S, et al. IAS 2015. Abstract MOAC0305LB. Daily PrEP 1 dose daily Time-Driven PrEP † 1 dose twice weekly + 1 dose after sex HIV-negative MSM and TGW* Event-Driven PrEP † 1 dose before and 1 dose after sex Lead-in period of directly observed therapy Final study visit TDF/FTC PrEP given at standard dose and dispensed using an electronic monitoring device. Adherence and sexual risk behavior assessed by weekly interview conducted by phone or in person. *Other inclusion criteria: reported anal intercourse and ≥ 1 other risk factor for HIV infection in last 6 mos; creatinine clearance > 70 mL/min. † Participants instructed to take no more than 2 doses daily or 7 doses/wk. Wk 34 Wk 30 Wk 0Wk 6

16 clinicaloptions.com/hiv Highlights of IAS 2015  179 MSM or TGW randomized –Daily PrEP, n = 59 –Time-driven PrEP, n = 60 –Event-driven PrEP, n = 60  Baseline characteristics: median age 30 yrs, 98% MSM, 70% black  HIV seroconversion seen in 2 pts –Both pts had low or undetectable TDF in dried blood spots/plasma at study visits HPTN 067/ADAPT: Harlem Cohort Comparison of PrEP Strategies Mannheimer S, et al. IAS 2015. Abstract MOAC0305LB. Reproduced with permission. *P =.001 vs daily. † P =.47 vs event driven. Complete coverage: taking ≥ 1 PrEP dose within 4 days before sex and ≥ 1 dose within 24 hrs after sex. 66 47* † 52 * 100 80 60 40 20 0 Complete Coverage (%) Daily Time driven Event driven Coverage of Sex Acts According to PrEP Strategy Pilule prise Avant acte Sexuel?

17 clinicaloptions.com/hiv Highlights of IAS 2015  Adherence significantly higher in daily dosing arm vs time-driven or event-driven arms (65% vs 46% vs 41%, respectively; P <.0001 for both comparisons)  Adherence did not differ significantly between the 2 nondaily dosing arms (P =.16) TFV in Dried Blood SpotsDoses Required vs Taken HPTN 067/ADAPT: Adherence to PrEP Strategies in Harlem Cohort Mannheimer S, et al. IAS 2015. Abstract MOAC0305LB. Reproduced with permission. Doses required: P <.0001 for all strategy-type comparisons Doses taken: P <.0001 for daily vs time-driven PrEP and event- driven vs daily PrEP; P =.33 when comparing nondaily dosing arms Low level: detectable to ≤ 350 fmol High level: > 350 fmol P =.07 for daily vs time-driven PrEP P =.01 for daily vs event-driven PrEP P =.36 for time-driven vs event-driven PrEP 8249 7K 5K 3K 1K 0 DailyTime Driven Event Driven 5526 3674 2468 2572 2356 Required tablets Tablets taken Number of Tablets 9K 80 60 40 20 0 100 % of Pts Reporting Sex in Last 7 Days (Wk 30) Undetectable Low level Higher level DailyTime Driven Event Driven 50 22 28 39 17 44 56 28 17

18 clinicaloptions.com/hiv Highlights of IAS 2015 HPTN 067/ADAPT: Bangkok Cohort Comparison of PrEP Strategies  178 MSM or TGW randomized –Daily PrEP, n = 60 –Time-driven PrEP, n = 59 –Event-driven PrEP, n = 59  Baseline characteristics: median age 31 yrs, 99% MSM, 100% Asian Holtz TH, et al. IAS 2015. Abstract MOAC0306LB. Reproduced with permission. *P =.02 vs daily arm, P =.04 vs time driven arm. Complete coverage defined as taking ≥ 1 PrEP dose within 4 days before sex and ≥ 1 dose within 24 hrs after sex. 100 80 60 40 20 0 85 84 74* Daily Time driven Event driven Coverage of Sex Acts According to PrEP Strategy Complete Coverage (%)

19 clinicaloptions.com/hiv Highlights of IAS 2015 HPTN 067/ADAPT: Adherence to PrEP Strategies in Bangkok Cohort  Doses required vs doses taken  Significantly higher adherence with daily (85%) and time-driven (79%) vs event-driven (65%) PrEP (P <.001)  Detectable levels of TFV in PBMCs were found in 91%, 95%, and 86% of pts in the daily, time-driven, and event-driven arms, respectively, at Wk 30 among participants reporting sex in past 7 days  HIV seroconversions observed in 2 pts during prerandomization directly observed dosing phase –Both associated with undetectable or low levels of FTC or TFV in plasma/PBMCs Doses required and taken: P <.001 for all strategy-type comparisons. Holtz TH, et al. IAS 2015. Abstract MOAC0306LB. Reproduced with permission. Number of Tablets Time Driven Event Driven 1928 2157 4121 3713 9420 8285 Required tablets Tablets reported taken Daily 10K 8K 6K 4K 2K 0

20 PrEP à l’Actuel N = 245 patients La majorité des patients recevant de la PrEP sont adherents au traitement et au suivi. Mais 23% arrêtent le tx, la moitié durant les premiers 3 mois. Une seule seroconversion, survenue durant les premiers jours du programme. Donc probablement avant le début du traitement. La PrEP n’a pas été reliée à une augmentation des comportements à risqué.

21 Au menu  Épidémiologie  Prévention  Nouveautés en traitement ARV  Complications de l’infection VIH et des traitements  Co-infection

22 Quand amorcer une thérapie ARV? Personnes symptomatiques (sida ou symptômes cliniques graves): –Commencer thérapie indépendamment de CD4 et CV Personnes asymptomatiques : COMITÉ CONSULTATIF POUR LA PRISE EN CHARGE DES PERSONNES VIVANT AVEC LE VIH Numération CD4 ECRACohortesTransmissionRecommandation < 250ACTG 320Recommandation forte pour les bénéfices cliniques (AI) Et forte pour transmission (AI) 250- 350CIPRA-HT 001 SMART HTPN 052 ART-CCHTPN 052 Partner >350SMARTHIV causal Cascade NA-Accord HTPN 052 Partner Recommandation Modérée pour les bénéfices cliniques (BII) Et Forte pour transmission (AI) COMITÉ CONSULTATIF POUR LA PRISE EN CHARGE DES PERSONNES VIVANT AVEC LE VIH

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25 5 continents, bonne répartition économique

26 ARV initiaux Chez ceux qui ont initié ARV plus rapidement: Atripla Plus tard, on note plus de RPV et RAL

27 Patients sur ARV / avec CV ≤ 200

28 Supériorité CD4 chez groupe Immédiat

29 Indice = Serious AIDS et non-AIDS

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32 Bref, traité tous les PVVIH, pour eux et pour prévenir la transmission!

33 Lignes directrices québécoises: amendement 2015! Moment préconisé pour faire commencer une thérapie antirétrovirale chez un patient asymptomatique Numération CD4ECRACohortesTransmissionRecommandation < 250ACTG 320 Recommandation forte pour les bénéfices cliniques (A ‑ I) et pour la transmission (A ‑ I) 250- 350 CIPRA-HT 001 SMART HTPN 052 ART-CC HTPN 052 Partner > 350SMART Temprano START HIV causal Cascade NA-Accord 33

34 Première intention: choix du traitement Le traitement de première intention devrait consister en l’une des trois combinaisons suivantes : –2 INTI et 1 INNTI –2 INTI et 1 IP/r –2 INTI et 1 INI Traitement de fond: 2 INTI 3 e composante: INNTI, IP ou INI Combinaisons préconisées -Abacavir + lamivudine (AI) -Tenofovir + emtricitabine (AI) -Dolutégravir (AI) -Raltégravir (AI) - Elvitégravir/cobicistat (BI) - Éfavirenz (BI) - Rilpivirine (BI) - Atazanavir/r (BI) - Darunavir/r DIE (BI) COMITÉ CONSULTATIF POUR LA PRISE EN CHARGE DES PERSONNES VIVANT AVEC LE VIH 34

35 clinicaloptions.com/hiv Integrating Recent Data When Selecting First-line Antiretroviral Therapy DHHS Guidelines: 2015 Recommended Regimens for First-line ART DHHS Guidelines. April 2015. Class DHHS Recommended Therapy Regardless of BL VL or CD4+ Count Alternative Regimens INSTI  RAL + TDF/FTC  EVG/COBI/TDF/FTC*  DTG/ABC/3TC †  DTG + TDF/FTC Boosted PI  DRV/RTV + TDF/FTC  ATV/RTV + TDF/FTC  ATV/COBI + TDF/FTC*  DRV/RTV + ABC/3TC †  DRV/COBI + ABC/3TC* †  DRV/COBI + TDF/FTC* NNRTI  EFV/TDF/FTC  RPV/TDF/FTC ‡ *Only for pts with pre-ART CrCl ≥ 70 mL/min. † Only for pts who are HLA-B*5701 negative. ‡ Not recommended in pts with baseline HIV-1 RNA > 100,000 copies/mL and CD4+ cell counts < 200 cells/mm 3.

36 clinicaloptions.com/hiv Highlights of IAS 2015  Multicenter, randomized, open-label trial [1] –Pts were Thai adults with baseline body weight of 59 kg (both arms) –Dose of ATV/RTV 200/100 mg has shown adequate pharmacokinetics in Thai pts [2] LASA: ATV/RTV 200/100 mg vs 300/100 mg 1. Bunupuradah T, et al. IAS 2015. Abstract TUAB0101. 2. Avihingsanon A, et al. Clin Pharmacol Ther. 2009;85:402-408. Thai pts with HIV-1 RNA < 50 copies/mL (≥ 12 mos) on boosted PI regimen for ≥ 3 mos (N = 550*) ATV/RTV 200/100 mg QD + 2 NRTIs (n = 273) ATV/RTV 300/100 mg QD + 2 NRTIs (n = 277) Stratified by site and use of tenofovir and indinavir Treatment Wk 48 *ITT/NC = F population.

37 clinicaloptions.com/hiv Highlights of IAS 2015 LASA: Key Results  Higher rate of discontinuations with ATV/RTV 300/100 mg vs ATV/RTV 200/100 mg (7.6% vs 2.6%; P =.01) ‒ ATV/RTV 300/100 mg associated with significantly higher mean total bilirubin and percentage of pts experiencing grade 3/4 hyperbilirubinemia (P <.001)  Estimated that treating 20,000 Thai HIV cases with ATV/RTV 200/100 mg instead of 300/100 mg would lead to a 5-yr savings of US$58 million (factoring in a 10% increase in cases/yr) ‒ Note: PK analysis has shown that the median AUC is 58% higher in Thai pts vs white pts at a dose of ATV/RTV 300/100 mg [2] HIV-1 RNA < 50 cells/mL (%) P =.03 NC = F 92 86 ATV/RTV 300/100 mg ATV/RTV 200/100 mg Difference in % Pts With HIV-1 RNA < 50 copies/mL Favors ATV/RTV 300/100 mg Favors ATV/RTV 200/100 mg P =.03 NC = F -10010 1. Bunupuradah T, et al. IAS 2015. Abstract TUAB0101. 2. Avihingsanon A et al. Clin Pharmacol Ther. 2009; 85:402-408. Dosage possible au Québec Option possible au lieu du retrait RTV?

38 ‡ Tenofovir Alafenamide (TAF): Novel Prodrug of Tenofovir † T 1/2 based on in vitro plasma data. 1. Lee W et. Antimicr Agents Chemo 2005;49(5):1898-1906. 2. Birkus G et al. Antimicr Agents Chemo 2007;51(2):543-550. 3. Babusis D, et al. Mol Pharm 2013;10(2):459-66. 4. Ruane P, et al. J Acquir Immune Defic Syndr 2013; 63:449-5. 5. Sax P, et al. JAIDS 2014. 2014 Sep 1;67(1):52-8. 6. Sax P, et al. Lancet 2015 Apr 15 [Epub ahead of print]. HIV TARGET CELL AMIDATE ESTER DIANION GI TRACT Tenofovir alafenamide (TAF) Tenofovir disoproxil fumarate (TDF) Tenofovir (TFV) Parent Nucleotide T 1/2 = 90 min † T 1/2 = 0.4 min † PLASMA TAF 25 mg TDF 300 mg TFV 91% lower TFV levels minimize renal and bone effects while maintaining high potency for suppressing HIV TFV HIV Gupta S, et al. IAS 2015, Vancouver, Canada. Oral # TUAB0103 38

39 ‡ Study Design Study 109: Suppressed Adults Switched from a TDF-containing regimen to E/C/F/TAF Treatment Naïve Patients Study 102 and 103 Phase 3, 96-week, multi-centered, randomized, open label, active-controlled HIV Suppressed FTC/TDF + 3rd Agent HIV-1 RNA <50 c/mL eGFR ≥ 50 mL/min Primary Endpoint : Non-inferiority (12% margin) of switch to E/C/F/TAF vs continuation of baseline regimen by FDA Snapshot analysis (HIV-1 RNA <50 copies/mL at week 48) Secondary Endpoints: Efficacy through Week 96 Safety and tolerability through Week 48 and Week 96" TDF-containing regimens Stribild (32%), Atripla (26%), RTV or COBI-boosted ATV+FTC/TDF (42%) ClinicalTrials.gov Identifier: NCT01815736. Secondary Endpoints Switch to E/C/F/TAF QD Continue FTC/TDF + 3 rd Agent Primary Endpoint Week 48Week 96 2:1 N=959 N=477 Key inclusion criteria HIV-1 RNA <50 c/mL for ≥6 months No HBV or HCV infection 39 E/C/F/TAF: single-tablet regimen elvitegravir 150mg/ cobicistat 150mg/ emtricitabine 200mg/ tenofovir alafenamide 10mg STB = Stribild = single-tablet regimen elvitegravir 150mg/ cobicistat 150mg/ emtricitabine 200mg/ tenofovir DF 300mg ATR = Atripla = single-tablet regimen efavirenz 600mg/ emtricitabine 200mg/ tenofovir DF 300mg ATV = atazanavir, COBI = cobicistat, RTV = ritonavir Mills A, et al. IAS 2015, Vancouver, Canada. Oral # TUAB0102

40 ‡ Virologic Outcomes (HIV-1 RNA <50 c/mL) at Week 48 40 Study 109: Suppressed Adults Switched from a TDF-containing regimen to E/C/F/TAF HIV-1 RNA < 50 c/mL, % FTC/TDF + 3 rd Agent (n=477) E/C/F/TAF (n=959) Favors FTC/TDF+3 rd AgentFavors E/C/F/TAF 6.7% -12% +12% 1.6% 0 Treatment Difference (95% CI) 4.1% Switching to E/C/F/TAF was statistically superior in efficacy compared to continuing FTC/TDF + 3 rd agent at Week 48 P <0.001 Mills A, et al. IAS 2015, Vancouver, Canada. Oral # TUAB0102

41 ‡ Change in Spine and Hip BMD Through Week 48 41 Study 109: Suppressed Adults Switched from a TDF-containing regimen to E/C/F/TAF Median % Change (Q1, Q3) from Baseline E/C/F/TAF FTC/TDF+3 rd Agent -0.28 -0.26 02448 Weeks Spine (N=1,369) Hip (N=1,354) Switching to E/C/F/TAF from a regimen containing FTC/TDF + 3 rd agent resulted in increases in spine and hip BMD at Week 48 Mills A, et al. IAS 2015, Vancouver, Canada. Oral # TUAB0102 ∆ 2.07 p <0.001 ∆ 1.63 p <0.001

42 ‡ Changes (%) in Quantitative Proteinuria at Week 48 42 Study 109: Suppressed Adults Switched from a TDF-containing regimen to E/C/F/TAF CR: creatinine; UPCR: urine protein creatinine ratio (mg/g); UACR: urine albumin: creatinine ratio;(mg/g); RBP: retinol-binding protein;(µg/g); β-2-m: beta-2 microglobulin (µg/g) E/C/F/TAF FTC/TDF+3 rd Agent RBP:Cr β-2-m:Cr UPCR UACR Tubular Proteinuria Each difference between treatment arms was statistically significant (p <0.001) Switching to E/C/F/TAF from a regimen containing FTC/TDF+3 rd agent resulted in significant decreases in proteinuria, albuminuria, and tubular proteinuria at Week 48 Mills A, et al. IAS 2015, Vancouver, Canada. Oral # TUAB0102

43 Donc… le nouveau ténofovir est  Aussi efficace  Plus sécuritaire pour les reins  Plus sécuritaire pour les os 43

44 ‡ STB (EVG/COBI/FTC/TDF): elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate ATV + RTV + FTC/TDF: atazanavir + ritonavir + emtricitabine/tenofovir disoproxil fumarate TVD: emtricitabine/tenofovir disoproxil fumarate Study Design WAVES: Women AntiretroViral Efficacy and Safety Study Squires K, et al IAS 2015. Vancouver, Canada. Poster # MOLBPE08 Primary endpoint: HIV-1 RNA < 50 c/mL at Week 48 by FDA Snapshot (non- inferiority margin of 12%). If non-inferiority is established, then superiority will be tested. Open Label Extension n =289 n =286 1:1 ATV+RTV+TVD ATV+RTV+TVD Placebo Week 48 STB STB Placebo Stratification: HIV-1 RNA -(≤100K, >100 to ≤ 400K, >400Kc/mL) Race (Black or non-Black) HIV-1 RNA ≥ 500 c/mL eGFR ≥ 70 mL/min No History of prior ART Sensitivity to FTC, TDF, ATV First all-women, international, randomized, double-blind, phase 3 trial 44

45 ‡ Virologic Outcomes (HIV-1 RNA <50 c/mL) at Week 48 45 WAVES: Women AntiretroViral Efficacy and Safety Study HIV-1 RNA < 50 c/mL, % ATV+ RTV + TVD (n=286) STB (n=289) Favors ATV+ RTVFavors STB -12% +12% 0.4% 0 12.6% Treatment Difference (95% CI) 6.5%  STB had statistically superior efficacy to ATV+RTV+TVD at Week 48 (difference 6.5%, 95% CI 0.4% to 12.6%)  Mean CD4 cell increase was 196 cells/mm3 (STB and ATV+RTV+TVD) Squires K, et al IAS 2015. Vancouver, Canada. Poster # MOLBPE08

46 Au menu  Épidémiologie  Prévention  Nouveautés en traitement ARV  Complications de l’infection VIH et des traitements  Co-infection

47 ‡ Study Design Phase 3, multi-center, single-arm, open label, 96-week study Primary Endpoint Change from baseline in glomerular filtration rate* † at W 24 Secondary Endpoints Efficacy, safety, and tolerability observed through W 48 and 96 Proportion of subjects with HIV-1 RNA <50 c/mL by FDA Snapshot analysis ClinicalTrials.gov Identifier: NCT01818596 Treatment Naïve Patients Study 102 and 103 Secondary Endpoints HIV Suppressed Adults Renal Impairment eGFR 30-69 mL/min Primary Endpoint Week 24Week 48 Key inclusion criteria Stable ART CD4 ≥ 50 cells/µL No HCV or HBV infection HIV-1 RNA <50 c/mL for ≥6 months N = 242. E/C/F/TAF QD *eGFR was measured using the Cockcroft-Gault formula (eGFR CG ) in all patients. † aGFR was measured at three timepoints (baseline, Week 2, 4 or 8 and Week 24) in a subset of patients. Week 96 Study 112: Renal Impairment in Adults: Sub-Group Analysis by Pre-Switch ARV Regimen (TDF vs. Non-TDF) 47 Gupta S, et al. IAS 2015, Vancouver, Canada. Oral # TUAB0103 QD=once daily, eGFR=estimated glomerular filtration rate, aGFR=actual glomerular filtration rate

48 ‡ Virologic Outcomes (HIV-1 RNA <50 c/mL) at Week 48 HIV-1 RNA < 50 c/mL, % *Seven subjects discontinued through Week 48 due to adverse events, seven discontinued due to administrative reasons, and three had missing virologic data but were on study drugs E/C/F/TAF (n =242) E/C/F/TAF maintained high rate of virologic suppression at Week 48 (222/242) (17/242) (3/242) Study 112: Renal Impairment in Adults: Sub-Group Analysis by Pre-Switch ARV Regimen (TDF vs. Non-TDF) 48 Pozniak A, et al. CROI 2015; Seattle, WA. #795

49 ‡ Proteinuria: Change From Baseline to Week 48 49 *All TDF Wk 48 vs. baseline changes statistically significant † All non-TDF Wk 48 vs. baseline changes not statistically significant. Median (mg/g) 105 188 UPCR UACR 41 18  -2-µG:Cr TDF*Non-TDF † Baseline Week 48 Median (µg/g) 197 1525 3477 399 Tubular Proteins RBP:Cr Study 112: Renal Impairment in Adults: Sub-Group Analysis by Pre-Switch ARV Regimen (TDF vs. Non-TDF) UPCR= Urine Protein:Creatinine Ratio UACR= Urine Albumin: Creatinine Ratio RBP:Cr= Retinol Binding Protein: Creatinine Ratio β-2-µG= Cr: β-2-microglobulin:Creatinine Ratio Significantly less proteinuria in patients switching to E/C/F/TAF from a TDF-based regimen Gupta S, et al. IAS 2015, Vancouver, Canada. Oral # TUAB0103

50 ‡ Change in Spine and Hip BMD Through Week 48 50 TDF Non-TDF *p<0.05 by two-sided Wilcoxon signed-rank test (Wk 48 vs. Baseline). Study 112: Renal Impairment in Adults: Sub-Group Analysis by Pre-Switch ARV Regimen (TDF vs. Non-TDF) Spine Hip Mean (SD) % Δ Spine BMD 2.95* 0.99 1.85* 0.70 Mean (SD) % Δ Hip BMD Week 24 n=226 Baseline n=236 Week 48 n=214 Week 24 n=225 Baseline n=236 Week 48 n=216 Progressive increases in spine and hip BMD through Week 48 Gupta S, et al. IAS 2015, Vancouver, Canada. Oral # TUAB0103 BMD=bone mineral density ∆ 1.96 ∆ 1.15

51 Donc… chez les patients avec des problèmes de fonction des reins…  le nouveau ténofovir est  Aussi efficace  Sécuritaire pour les reins  Plus sécuritaire pour les os 51

52 Au menu  Épidémiologie  Prévention  Nouveautés en traitement ARV  Complications de l’infection VIH et des traitements  Co-infection

53 ‡ Study Design Phase 3, 48-week, multicentered, single-arm, open label study Efficacy Endpoint Proportion with HIV RNA <50 copies/mL (Snapshot) and HBV DNA <29 IU/mL (missing=failure) at W24 and W48 Safety Endpoints Safety and tolerability through W24 and W48, ALT normalization, HBsAg to HBsAb and HBeAg to HBeAb seroconversion, and changes in liver fibrosis stage** ClinicalTrials.gov Identifier: NCT02071082 Treatment Naïve Patients Study 102 and 103 Key inclusion criteria † HIV-1 RNA <50 c/mL for ≥6 months ‡ HBV DNA ≤9 log 10 (+HBsAg for ≥6 months) N = 72* *Two subjects were ineligible for enrollment because they did not meet the definition of chronic HBV infection (discovered after study enrollment). Therefore, the full safety analysis set included all 74 subjects, but the final efficacy analysis set excluded these two subjects, leading to a final efficacy analysis set of 72 subjects. **By FibroTest. Secondary Endpoint Primary Endpoint Week 24Week 48 E/C/F/TAF QD Study 1249: HIV/HBV Co-infected Adults on E/C/F/TAF HIV Suppressed † & HBV-Infected ‡ Adults eGFR ≥50 mL/min 53 Gallant J, et al. IAS 2015, Vancouver, Canada. Poster # WELBPE13

54 ‡ Summary of Efficacy and Safety Endpoints Through Week 48 Switch to E/C/F/TAF in HIV/HBV co-infected patients demonstrated robust HIV and HBV suppression with favourable effects on liver safety endpoints 54 Study 1249: HIV/HBV Co-infected Adults on E/C/F/TAF Gallant J, et al. IAS 2015, Vancouver, Canada. Poster # WELBPE13 Patients (%) Baseline Week 48 *4/8 patients with available ALT data at W48 † 35/60 patients with paired baseline and W48 data

55 Le traitement de l’hépatite C chez le PVVIH  Abandon quasi-complet de l’interféron  Traitements 1 re ligne passés de 24-48 (72) semaines à 12-24 semaines  Plusieurs traitements sans ribavirine: moins d’anémie, fatigue  Nouveaux traitements nettement mieux tolérés  Remboursement par la RAMQ se fera de façon graduelle: cirrhotiques, cas avec complications… éventuellement tous!

56 Choix du traitement  Selon le génotype (1 à 6, a,b…)  Selon que la personne ait été traitée ou non par le passé  Selon la présence ou non de cirrhose  Succès: de 90 à 100% dans les études  Sofosbuvir/ledipasvir (Harvoni) (±RBV)  Paritaprévir-ritonavir/ombitasvir + dasabuvir (Holkira pack) (±RBV)  Sofosbuvir/daclatasvir

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60 Succès similaires selon ARV Aucun effet indésirable menant à D/C

61 Nouvelle combinaison de Merck: grazoprevir + elbasvir  Efficace  Bien toléré  Efficacité démontrée chez VHC seule ou co-infection VIH/VHC  Devrait être commercialisé sous peu  Espérons un prix « raisonnable » …

62 Résumé de l’IAS 2015  Prévention: traiter personnes atteintes et autres mesures  PrEP: en continue vs à la demande (différentes méthodes)  Quand débuter ARV chez PVVIH? Traiter tout le monde, pour eux et pour prévenir les nouvelles infections  Stribild > ATV chez les femmes  ATV/R 200/100 pour certains cas?

63 Résumé de l’IAS 2015  E/C/F/TAF:  En transfert pour patients sur Atripla, Stribild, RTV ou COBI/ATV+FTC/TDF  Chez patients avec insuffisance rénale chronique  Chez patients co-infectés VHB  Nouveau combo pour VHC chez VIH: - grazoprevir/elbasvir x 12 semaines

64 Remerciements  Support pour diapositives:  CCO  Gilead  Merck  ViiV healthcare

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