1. clinicaloptions.com/hiv Fall 2014 HIV Update ATV/COBI + TDF/FTC vs ATV/RTV + TDF/FTC: 144-Wk Report  Randomized, double-blinded phase III study  Primary endpoint: HIV-1 RNA < 50 c/mL at Wk 48 –Cobicistat noninferior to ritonavir at Wk 48 by FDA snapshot ITT analysis with HIV-1 RNA < 50 c/mL in 85.2% vs 87.4% [1] ART-naive pts with HIV-1 RNA ≥ 5000 c/mL, any CD4+ cell count, eGFR ≥ 70 mL/min (N = 692)  ATV 300 mg QD + COBI 150 mg QD +  TDF/FTC 300/200 mg QD  (n = 344) Wk 144 [2] ATV 300 mg QD + RTV 100 mg QD + TDF/FTC 300/200 mg QD (n = 348) Stratified by screening HIV-1 RNA ≤ vs > 100,000 c/mL 1. Gallant JE, et al. J Infect Dis. 2013;208:32-39. 2. Gallant JE, et al. ICAAC 2014. Abstract H-647. Wk 48: Primary Endpoint [1]

2. clinicaloptions.com/hiv Fall 2014 HIV Update ATV/COBI + TDF/FTC vs ATV/RTV + TDF/FTC: Wk 144 FDA Snapshot (ITT)  Mean CD4+ cell count increase with cobicistat vs ritonavir: 310 vs 332 cells/mm 3 Gallant JE, et al. ICAAC 2014. Abstract H-647. Reproduced with permission. *No data include study drug discontinuation for adverse event/death, study drug discontinuation for other reasons with last available HIV-1 RNA < 50 c/mL, or missing data during window. Virologic Success Virologic Failure 100 80 60 40 20 0 Pts (%) 85 87 78 79 72 74 6 4 7 5 8 5 9 9 15 16 20 21 W48W96W144W48W96W144W48W96W144 No Data* COBI (n = 344) RTV (n = 348) 95% Cl for Difference Favors ATV + RTV Favors ATV + COBI -2.2 3.0-7.4 4.7 -7.6 -8.74.5 -2.1 -1.4 W48 W96 W144 -12%12%0

3. clinicaloptions.com/hiv Fall 2014 HIV Update ATV/COBI + TDF/FTC vs ATV/RTV + TDF/FTC: Serum Creatinine and eGFR  Additional renal AEs leading to study drug discontinuation from Wk 96-144 included 1 case of proximal renal tubulopathy in ritonavir arm and 2 cases of isolated Cr increase in COBI arm Gallant JE, et al. ICAAC 2014. Abstract H-647. Reproduced with permission. 0.4 0.3 0.2 0.1 0.0 -0.1 -0.2 20 10 0 -10 -20 -30 -40 BL24487296120144 -15.1 -13.7 -12.9 -9.1 -8.3 -7.5 Wk Change in eGFR (mL/min) at Wk 144 COBI: -15 vs RTV: -8 Change in eGFR, Median [IQR] 0.13 Change in Serum Creatinine, Median [IQR] BL24487296120144 Wk Change in Cr (mg/dL) at Wk 144 COBI: 0.13 vs RTV: 0.07 0.07 0.080.09 0.13 0.12 COBIRTV mg/dLmL/min

4. clinicaloptions.com/hiv Fall 2014 HIV Update  No difference in TC:HDL ratio changes between arms  Additional treatment-emergent resistance from Wk 96 to Wk 144 in 9 pts in COBI arm vs 7 pts in RTV arm –No cases of primary PI resistance through Wk 144 ATV/COBI + TDF/FTC vs ATV/RTV + TDF/FTC: Lipids and Resistance Gallant JE, et al. ICAAC 2014. Abstract H-647. Reproduced with permission. TCLDL HDL TG P =.35 P =.11 P =.49 20 15 10 5 0 Median Change at Wk 144 (mg/dL) COBI RTV

5. clinicaloptions.com/hiv Fall 2014 HIV Update Dolutegravir Phase III Trials in Treatment- Naive Pts  Randomized, noninferiority phase III studies  Primary endpoint: HIV-1 RNA < 50 c/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 [1] (active controlled, double blind) SINGLE [2] (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 [3] (open label) 1. Raffi F, et al. Lancet. 2013;381:735-743. 2. Pappa K, et al. ICAAC 2014. Abstract H-647a. 3. Molina JM, et al. Glasgow HIV 2014. Abstract O153.

6. clinicaloptions.com/hiv Fall 2014 HIV Update SINGLE: DTG + ABC/3TC Superior to EFV/TDF/FTC at Both Wk 48 and 144  AE-related study d/c: 4% in DTG vs 14% in EFV arm  Resistance through Wk 144: 0 pts with treatment-emergent resistance mutations in DTG arm; 1 pt with NRTI and 6 pts with NNRTI resistance mutations in EFV arm  CD4+ count increase at Wk 144 greater with DTG: +379 vs +332 cells/mm 3 (P =.003)  Separate PK study showed plasma metformin AUC 1.8-fold higher when coadministered with DTG [3] HIV-1 RNA < 50 c/mL (%) 88 81 DTG + ABC/3TC EFV/TDF/FTC 71 63 Wk 48 [1] Wk 144 [2] 364/ 414 338/ 419 Δ 8.3% (2.0-14.6; P =.01) Δ 7% (2.5-12.3; P =.003) 0 20 40 60 80 100 n/N = 1. Walmsley S, et al. N Engl J Med. 2013;369:1807-1818. 2. Pappa K, et al. ICAAC 2014. Abstract H-647a. 3. Zong J, et al. Glasgow HIV P052. 296/ 414 265/ 419

7. clinicaloptions.com/hiv Fall 2014 HIV Update FLAMINGO: DTG + 2 NRTIs Superior to DRV/RTV + 2 NRTIs at Both Wk 48 and 96  AE-related study d/c: 3% in DTG arm vs 6% in DRV/RTV arm  No pts with treatment-emergent resistance mutations in either arm through Wk 96  Mean change in serum creatinine from BL to Wk 96 higher with DTG vs DRV/RTV: 15.35 μmol/L vs 3.93 μmol/L –Caused by known inhibition of tubular creatinine secretion HIV-1 RNA < 50 c/mL (%) 90 83 0 20 40 60 80 100 80 68 Wk 48 [1] Wk 96 [2] Δ 12.4% (4.7-20.2; P =.002) Δ 7.1% (0.9-13.2; P =.025) n/N = DTG + NRTIs (n = 242) DRV/RTV + NRTIs (n = 242) 1. Clotet B, et al. Lancet. 2014;383:2222-2231. 2. Molina JM, et al. Glasgow HIV 2014. Abstract O153. Reproduced with permission. 217/ 242 200/ 242 NR

8. clinicaloptions.com/hiv Fall 2014 HIV Update FLAMINGO: Wk 96 Subgroup Efficacy Analysis Molina JM, et al. Glasgow HIV 2014. Abstract O153. Reproduced with permission. HIV-1 RNA < 50 c/mL (%) DTG + NRTIs (n = 242) DRV/RTV + NRTIs (n = 242) 82 75 79 64 52 82 73 80 68 80 100 80 60 40 20 0 TDF/FTC (n = 325) ABC/3TC (n = 159) > 100,000 (n = 122) ≤ 100,000 (n = 362) Overall BL HIV-1 RNA (c/mL)Background NRTI

9. clinicaloptions.com/hiv Fall 2014 HIV Update FLAMINGO: Lipid Changes With DTG vs DRV/RTV Through Wk 96  Higher rate of grade ≥ 2 fasting LDL abnormalities by Wk 96 with DRV/RTV vs DTG: 22% vs 7% (P <.001) Molina JM, et al. Glasgow HIV 2014. Abstract O153. Reproduced with permission. DTG + NRTIs (n = 242) DRV/RTV + NRTIs (n = 242) 0.4 0.3 0.2 0.1 0 0.8 0.6 0.4 0.2 0 -0.2 Total Cholesterol LDL Cholesterol Triglycerides Mean Change From BL (mmol/L) Mean Change From BL TC:HDL Ratio

10. clinicaloptions.com/hiv Fall 2014 HIV Update ENCORE1: EFV 400 vs 600 mg QD + TDF/FTC in Treatment-Naive Pts  Randomized, double-blind, noninferiority study  Primary endpoint: HIV-1 RNA < 200 c/mL at Wk 96 Carey D, et al. Glasgow HIV 2014. Abstract O421. ART-naive pts with HIV-1 RNA ≥ 1000 c/mL, CD4+ cell count > 50 to < 500 cells/mm 3, CrCl ≥ 50 mL/min (N = 630)  EFV 400 mg QD + TDF/FTC 300/200 mg QD  (n = 321) Wk 96 EFV 600 mg QD + TDF/FTC 300/200 mg QD (n = 309) Stratified by screening HIV-1 RNA ≤ vs > 100,000 c/mL and study site

11. clinicaloptions.com/hiv Fall 2014 HIV Update ENCORE1: EFV 400 mg QD Noninferior to 600 mg QD Through 96 Wks  Mean change in CD4+ cell count from BL greater with 400-mg vs 600-mg EFV (P =.03)  Rate of EFV-related AEs lower with 400-mg vs 600-mg dose: 37.7% vs 47.9% (P =.01)  Trend toward lower rate of discontinuation for EFV-related AEs with 400-mg vs 600-mg dose: 8.3% vs 15.5% (P =.07)  Frequency of treatment emergent NNRTI resistance similar in both arms Carey D, et al. Glasgow HIV 2014. Abstract O421. Reproduced with permission. 0.0 -0.5 -1.5 -2.0 -2.5 -3.0 -3.5 -4.0 01224364860728496 321 309 316 302 312 301 310 299 312 295 307 291 304 290 300 289 299 286 Pts at Risk, n EFV 400 mg EFV 600 mg Mean difference: -0.02 log 10 c/mL (95% Cl: -0.14 to 0.10; P =.74) Change From BL (HIV-1 RNA log 10 c/mL) Wk EFV 600 mg QD + TDF/FTC EFV 400 mg QD + TDF/FTC

12. clinicaloptions.com/hiv Fall 2014 HIV Update  Insurance claims data obtained from commercial insurance database and multistate Medicaid database  Suicidality determined by medical coding  Primary outcome: suicidality (coded as suicidal ideation or suicide attempt)  Secondary outcomes –Suicide attempt (coded as suicide and self-inflicted injury) –Injuries consistent with suicide attempt (coded as poisoning, open wounds, asphyxiation)  Adjusted HR for primary outcome of suicidality (vs EFV-free regimens) –Commercial database: 1.03 (95% CI: 0.64-1.67) –Medicaid database: 0.90 (95% CI: 0.62-1.32) Nkhoma E, et al. IDWeek 2014. Abstract 646. Real-World Assessment of Suicidality Risk Among Pts Initiating EFV

13. clinicaloptions.com/hiv Fall 2014 HIV Update Real-World Assessment of Suicidality Risk Among Pts Initiating EFV Nkhoma E, et al. IDWeek 2014. Abstract 646. Pt Characteristic CommercialMedicaid EFV (n = 11,187) EFV Free (n = 8796) P Value EFV (n = 2224) EFV Free (n = 2930) P Value Age, yrs (SD) 40.1 (10.4)40.8 (10.4)<.00141.7 (11.5)39.7 (11.6)<.001 Male, % 86.079.1<.00156.750.2<.001 Any hospitalization, % 15.514.1.00726.124.3.152 Diabetes, % 5.0.90510.79.1.046 Pain disorders, % 12.512.9.48022.522.4.960 AIDS-defining illness, % 10.58.8<.00119.018.2.454 Suicidality, % 0.20.4<.0011.32.9<.001 Depression, % 16.720.0<.00129.034.8<.001 Drug dependence, % 0.60.9.0175.38.1<.001 Anxiety, % 2.33.1<.0013.85.5.005 Schizophrenia, % 0.040.1.0133.77.0<.001 On 2nd-gen antipsychotics, % 0.81.5<.0015.89.4<.001 On antidepressants, % 10.512.2<.00115.616.8.247

14. clinicaloptions.com/hiv Fall 2014 HIV Update PROTEA: Switch to DRV/RTV ± 2 NRTIs for Stably Suppressed Pts on First-line ART  Multicenter, randomized, open-label phase IIIb study  Primary endpoint: HIV-1 RNA < 50 c/mL at Wk 48 (ITT; FDA Snapshot)  Average duration of initial ARV regimen: 5.5 yrs HIV-infected pts virologically suppressed (HIV-1 RNA < 50 c/mL) on first-line ART; CD4+ nadir > 100 cells/mm 3 (N = 273)  DRV 800 mg QD + RTV 100 mg QD  (n = 137) Wk 48 DRV 800 mg QD + RTV 100 mg QD + 2 NRTIs* (n = 136) Stratified by HCV status *Investigator-selected dual combination of either ABC, 3TC, ZDV, TDF, or FTC. Antinori A, et al. Glasgow HIV 2014. Abstract O423A. Clarke A, et al. Glasgow HIV 2014. Abstract O423B.

15. clinicaloptions.com/hiv Fall 2014 HIV Update PROTEA: Virologic Response at Wk 48  No difference in efficacy between treatment arms in “switch included” analysis that classified pts with viral suppression at Wk 48 after reintensification or second switch as virologic responders HIV-1 RNA < 50 c/mL (%) DRV/RTVDRV/RTV + 2 NRTIs 118/ 137 129/ 136 27/ 41 29/ 30 91/ 96 100/ 106 100 80 60 40 20 0 ITT: -8.7% (-1.8% to -15.5%) 86.1 94.9 100 80 60 40 20 0 65.9 96.7 94.894.3 Nadir CD4+ Count < 200 cells/mm 3 Nadir CD4+ Count ≥ 200 cells/mm 3 HIV-1 RNA < 50 c/mL (%) DRV/RTVDRV/RTV + 2 NRTIs DRV/RTVDRV/RTV + 2 NRTIs n/N = Antinori A, et al. Glasgow HIV 2014. Abstract O423A. Clarke A, et al. Glasgow HIV 2014. Abstract O423B. Reproduced with permission.

16. clinicaloptions.com/hiv Fall 2014 HIV Update Antinori A, et al. Glasgow HIV 2014. Abstract O423A. Clarke A, et al. Glasgow HIV 2014. Abstract O423B. Reproduced with permission. PROTEA: Adverse Events Event, n (%)DRV + RTV (n = 137) DRV + RTV + 2 NRTIs (n = 136) Serious AEs9 (6.6)5 (3.7) Deaths*1 (0.7)0 All AEs96 (70.1)83 (61) Grade 3/4 AEs7 (5.1)3 (3.7) Psychiatric AEs10 (7.3)9 (6.6) Nervous system AEs13 (9.5)14 (10.3) *1 pt with myocardial infarction judged to be unrelated to treatment.

17. clinicaloptions.com/hiv Fall 2014 HIV Update DRV/COBI/FTC/Tenofovir Alafenamide vs DRV + COBI + FTC/TDF  Randomized, double-blind, placebo-controlled phase II study  Primary endpoint: HIV-1 RNA < 50 c/mL at Wk 24 (FDA snapshot, ITT)  TAF: novel tenofovir prodrug, yields higher tenofovir diphosphate levels and lower plasma tenofovir levels vs TDF Mills A, ICAAC 2014. Abstract H-647c. ART-naive pts with HIV-1 RNA ≥ 5000 c/mL, CD4+ cell count > 50 cells/mm 3, eGFR > 70 mL/min (N = 153)  DRV/COBI/FTC/TAF 800/150/200/10 mg QD  (n = 103) Wk 48 DRV 800 mg QD (two 400-mg tablets) + COBI 150 mg QD + FTC/TDF 200/300 mg QD (n = 50) Wk 24

18. clinicaloptions.com/hiv Fall 2014 HIV Update DRV/COBI/FTC/TAF vs DRV + COBI + FTC/TDF: Virologic Suppression  No cases of emergent drug resistance among 8 pts with viral rebound  PBMC tenofovir diphosphate levels 6.5-fold higher in TAF vs TDF arm  Plasma tenofovir exposure 91% lower in TAF vs TDF arm Mills A, ICAAC 2014. Abstract H-647c. Reproduced with permission. HIV-1 RNA < 50 c/mL (%) 75 74 84 77 20 24 16 12 5 2 8 4 100 80 60 40 20 0 Tx Wk: 48 Virologic Success Virologic Failure No Data DRV/COBI/FTC/TAF DRV + COBI + FTC/TDF Weighted Difference (95% CI) Wk 24: 3.3 (-11.4 to 18.1) Wk 48: -6.2 (-19.9 to 7.4) 24 48244824

19. clinicaloptions.com/hiv Fall 2014 HIV Update DRV/COBI/FTC/TAF vs DRV + COBI + FTC/TDF: AEs and Lipid Changes  2 pts in each arm discontinued treatment for AEs –DRV/COBI/FTC/TAF: rash, substance dependence –DRV + COBI + FTC/TDF: worsening diarrhea, proximal renal tubulopathy  Significantly greater increases in TC (P <.001), LDL cholesterol (P <.001), and HDL cholesterol (P =.009) in TAF vs TDF arm; triglycerides increased in TAF arm vs small decrease in TDF arm (P =.007) Mills A, ICAAC 2014. Abstract H-647c. Reproduced with permission. AE Occurring in ≥ 10% Pts in TAF-Containing Arm, n (%) DRV/COBI/FTC/TAF (n = 103) DRV + COBI + FTC/TDF (n = 50) Diarrhea22 (21)13 (26) Fatigue14 (14)9 (18) Nausea13 (13)5 (10) Rash12 (12)4 (8)

20. clinicaloptions.com/hiv Fall 2014 HIV Update  Lower mean increase in serum creatinine from BL to Wk 48 in TAF vs TDF arm: 0.06 mg/dL vs 0.09 mg/dL (P =.053)  Less renal tubular proteinuria in TAF vs TDF arm (P =.003 for retinol binding protein/creatinine; P =.002 for β 2 -microglobulin/creatinine) DRV/COBI/FTC/TAF vs DRV + COBI + FTC/TDF: Other Outcomes Mills A, ICAAC 2014. Abstract H-647c. Reproduced with permission. 3 2 1 0 -2 -3 -4 -5 P ≤.001 -0.53 -2.09 -3.82 -0.84 2448BL Wks Hip Mean % Change (95% CI) in BMD From BL 3 2 1 0 -2 -3 -4 -5 2448BL Wks Spine P ≤.001 P ≤.003 -1.09 -3.86 -1.57 -3.62 DRV/COBI/FTC/TAF DRV + COBI + FTC/TDF

21. clinicaloptions.com/hiv Fall 2014 HIV Update AI438011: BMS-663068 in Treatment- Experienced Pts  Phase IIb study; primary endpoint: HIV-1 RNA < 50 c/mL at Wk 24  BMS-663068: HIV-1 attachment inhibitor prodrug, metabolized to BMS-626529  BMS-626529: novel HIV-1 attachment inhibitor; proposed MOA: binds gp120 to prevent viral attachment and host CD4+ cell entry; active against R5, R4, and dual tropic HIV-1 Brinson C, et al. Glasgow HIV 2014. Abstract O432A. BMS-663068 400 mg BID* + RAL + TDF (n = 50) BMS-663068 800 mg BID* + RAL + TDF (n = 49) BMS-663068 600 mg QD* + RAL + TDF (n = 51) BMS-663068 1200 mg QD* + RAL + TDF (n = 50) ATV/RTV 300/100 mg QD + RAL + TDF (n = 51) ART-exp’d pts with HIV-1 RNA ≥ 1000 c/mL, CD4+ cell count > 50 cells/mm 3, BMS-626529 IC 50 < 100 nM (N = 251) *Trial also included 7-d BMS-663068 monotherapy substudy (10 pts/arm) before initiating combination therapy; mean HIV-1 RNA decrease with monotherapy: 0.7-1.5 log 10 c/mL. Wk 96

22. clinicaloptions.com/hiv Fall 2014 HIV Update BMS-663068 in Treatment-Experienced Pts: Virologic Efficacy and AEs  Virologic response rates generally similar across BMS- 663068 dose arms and ATV/RTV arm –Rates numerically lower with BL HIV-1 ≥ 100,000 c/mL vs BL HIV-1 RNA < 100,000 c/mL except in BMS-663068 1200 mg QD arm  Virologic response rates generally similar across BMS- 626529 baseline IC 50 subgroups, but few pts in some subgroups  BMS-663068 arms: 4 pts discontinued for AEs; 4% to 8% experienced serious AEs Brinson C, et al. Glasgow HIV 2014. Abstract O432A.

23. clinicaloptions.com/hiv Fall 2014 HIV Update Protocol 007: Doravirine + TDF/FTC in Treatment-Naive Pts  Randomized, double-blind, 2-part, dose-finding phase II study  Safety endpoints: CNS AEs at Wk 8; AEs and laboratory parameters Wk 48; efficacy endpoints: HIV-1 RNA < 40 c/mL, < 200 c/mL and CD4+ cell count change at Wk 48 Gatell JM, et al. Glasgow HIV 2014. Abstract O434. Doravirine 25 mg QD (n = 41) Doravirine 50 mg QD (n = 43) Doravirine 100 mg QD (n = 42) Doravirine 200 mg QD (n = 41) Efavirenz 600 mg QD (n = 43) Part 1: ART-naive pts with HIV-1 RNA ≥ 1000 c/mL, CD4+ cell count ≥ 100 cells/mm 3 (N = 210) Part 2: ART-naive pts with HIV-1 RNA ≥ 1000 c/mL, CD4+ cell count ≥ 100 cells/mm 3 (N = 132) Doravirine 100 mg QD Efavirenz 600 mg QD Doravirine 100 mg QD (n = 66) Efavirenz 600 mg QD (n = 66) Wk 96 Wk 48Wk 36

24. clinicaloptions.com/hiv Fall 2014 HIV Update Doravirine + TDF/FTC: Virologic Response by Baseline HIV-1 RNA  Part 1: ad hoc analysis, Wk 48 (observed failure) Gatell JM, et al. Glasgow HIV 2014. Abstract O434. Reproduced with permission. Baseline HIV-1 RNA ≤ 100,000 c/mL Baseline HIV-1 RNA > 100,000 c/mL 88 89 86 85 87 74 25272827 107 27 96 89 91 82 2527282710727 < 40 c/mL< 200 c/mL< 40 c/mL< 200 c/mL 64 73 92 73 83 91 73 100 92 89 92 11 12451211 124512 100 80 60 40 20 0 n = Pts (%) DOR 25 mgDOR 50 mgDOR 100 mgDOR 200 mg All DOR EFV Wk 48 HIV-1 RNA

25. clinicaloptions.com/hiv Fall 2014 HIV Update Doravirine + TDF/FTC: Wk 48 Resistance Gatell JM, et al. Glasgow HIV 2014. Abstract O434. Reproduced with permission. Outcome, n (%)Doravirine, All Doses (n = 166) Efavirenz 600 mg (n = 42) Virologic failure* ≥ 40 c/mL27 (16.3)6 (14.3) Virologic failure* ≥ 200 c/mL6 (3.6)1 (2.4)  Resistance testing performed † 6 (3.6)1 (2.4)  NNRTI mutations detected (K101K/E)1 (0.6) ‡ 0  NRTI mutations detected00 *Virologic failure: nonresponse (HIV-1 RNA 1 wk apart or after Wk 24 in pts with initial response). † HIV-1 RNA > 500 c/mL required for resistance testing. ‡ HIV-1 RNA resuppressed at Wk 48 but rebounded; pt discontinued due to noncompliance.

26. clinicaloptions.com/hiv Fall 2014 HIV Update TURQUOISE-I: Paritaprevir/RTV/Ombitasvir + Dasabuvir + RBV in HIV/GT1 HCV Pts  Open-label phase II/III trial  Inclusion criteria: GT1; compensated cirrhosis (Child-Pugh A) allowed; DAA naive but pegIFN/RBV naive or experienced; HIV-1 RNA < 40 c/mL on ATV or RAL regimen; CD4+ cell count ≥ 200 or %CD4+ ≥ 14%  52% on ATV, 48% on RAL in 12-wk arm; 38% on ATV, 62% on RAL in 24-wk arm; 19% with cirrhosis  Primary endpoint: SVR12 Paritaprevir/RTV/Ombitasvir + Dasabuvir + RBV (n = 32) Paritaprevir/RTV/Ombitasvir + Dasabuvir + RBV (n = 31) Wk 24 Paritaprevir/RTV/ombitasvir 150/100/25 mg once daily; dasabuvir 250 mg twice daily; RBV 1000-1200 mg/day. DAA-naive HIV-infected pts with GT1 HCV infection (N = 63) Wk 12 Eron JJ, et al. Glasgow HIV 2014. Abstract O222.

27. clinicaloptions.com/hiv Fall 2014 HIV Update TURQUOISE-I: Efficacy (ITT) and Resistance Results  VF with RAVs in all 3 HCV target genes occurred in 2 pts with genotype 1a HCV, previous null response to pegIFN/RBV, and cirrhosis  VF (posttreatment) without RAVs occurred in 2 HCV treatment-naive pts with genotype 1a HCV –Genetic analysis strongly supported HCV reinfection with different isolate –Both pts MSM who reported high-risk sexual practices posttreatment Eron JJ, et al. Glasgow HIV 2014. Abstract O222. Reproduced with permission. 12 wks (n = 31) 24 wks (n = 32) SVR12 (%) n/N = *2 pts in 24-wk arm had HCV viremia recurrence suspected to be caused by HCV reinfection. 100 80 60 40 20 0 OverallAtazanavirRaltegravir 29/ 31 29/ 32 15/ 16 12/ 12 14/ 15 17/ 20 93.5 90.6 93.8 100 93.3 85.0*

28. clinicaloptions.com/hiv Fall 2014 HIV Update Paritaprevir/RTV/Ombitasvir + Dasabuvir: Drug–Drug Interactions With ART  Randomized, multiple-dose phase I study in healthy volunteers 1. Khatri A, et al. ICAAC 2014. Abstract V-483. 2. Khatri A, et al. ICAAC 2014. Abstract V-484. Coadministered Drugs*Days Clinically Relevant PK Interactions Recommended Dose Adjustments Safety/Tolerability Concerns 3 DAAs + FTC/TDF [1] 7-14 None 3 DAAs + RAL [1] 14 None 3 DAAs + RPV [1] 14 ↑ RPV exposureDo not coadministerNone Paritaprevir/RTV + dasabuvir + EFV/FTC/TDF [1] 14 NADo not coadminister 9/16 discontinued for AEs (GI and ALT/AST ↑) 3 DAAs + ATV + RTV QAM or QPM [2] 14 None 3 DAAs + DRV + RTV (QAM, QPM, or BID) [2] 14 None 3 DAAs + LPV/RTV (QPM or BID) [2] 14 None; RTV dose 300 mg/day due to dual RTV-containing FDCs Do not coadministerIncrease GI AEs *Paritaprevir/RTV/ombitasvir administered in morning, dasabuvir dosed morning and evening; RTV dosed with ATV and DRV omitted when administering in the morning because of RTV presence in 3 DAAs.

29. clinicaloptions.com/hiv Fall 2014 HIV Update Kaiser Permanente HIV Care Cascade in 2010-2012 According to Age and Sex  CDC data show HIV care performance differs by age and sex [1]  KP integrated care system includes 9 states plus Washington DC, > 9 million members, > 22,000 HIV-infected members in 2013  Data show improved care performance in KP system vs CDC report [2]  Current analysis investigated differences in HIV care performance by age or sex among KP members 13 yrs of age or older with ≥ 8 mos of membership in study yr from 2010-2012 [3] –Male: 87% –Aged younger than 35 yrs: 10% to 11%; aged 35-54 yrs: 57% to 61%; aged 55 yrs or older: 29% to 32% 1. CDC fact sheet: HIV in the United States: the stages of care. 2012. 2. Horberg M, et al. CROI 2013. Abstract 1033. 3. Horberg M, et al. IDWeek 2014. Abstract 88.

30. clinicaloptions.com/hiv Fall 2014 HIV Update HIV Care Cascade Measured Over Multiple Time Periods Varies by Age and Sex  Higher rate of linkage to care, ART prescription, and viral suppression in men vs women in 2010 and 2011, but no significant difference between sexes in 2012; higher rate of retention in care in women vs men in all yrs  Higher rates of retention in care, ART prescription, and viral suppression with older age in all 3 yrs Horberg M, et al. IDWeek 2014. Abstract 88. Reproduced with permission. *Care linkage: visit/CD4+ count within 90 days of diagnosis/enrollment. † Care retention: ≥ 2 medical visits ≥ 60 days apart. 100 80 60 40 20 0 201020112012201020112012201020112012201020112012 Linked to Care*Retained in Care † Filled ART ≥ 3 MosHIV-1 RNA < 200 c/mL at Last Measure Aged younger than 35 yrsAged 35-54 yrsAged 55 yrs and older Completed Care Step (%) P <.05