1. July 19-22, 2015 Vancouver, Canada Highlights of IAS 2015 CCO Official Conference Coverage of the 8th IAS Conference on HIV Pathogenesis, Treatment, and Prevention* *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. This program is supported by an independent educational grant from Bristol-Myers Squibb, Gilead Sciences, Merck, and ViiV.

2. clinicaloptions.com/hiv Highlights of IAS 2015 Faculty Andrew Carr, MBBS, MD, FRACP, FRCPA Professor of Medicine University of New South Wales Director HIV, Immunology, and Infectious Disease Unit St Vincent's Hospital Sydney, Australia Joel E. Gallant, MD, MPH Medical Director of Specialty Services Southwest CARE Center Santa Fe, New Mexico Adjunct Professor of Medicine Division of Infectious Diseases Johns Hopkins University School of Medicine Baltimore, Maryland Anton L. Pozniak, MD, FRCP Consultant Physician Director of HIV Services Department of HIV and Genitourinary Medicine Chelsea and Westminster Hospital NHS Foundation Trust London, United Kingdom

3. clinicaloptions.com/hiv Highlights of IAS 2015 Disclosures Andrew Carr, MBBS, MD, FRACP, FRCPA, has disclosed that he has received consulting fees, funds for research support, and fees for non- CME/CE services from Gilead Sciences, MSD, and ViiV and funds for research support from Pfizer. Joel E. Gallant, MD, MPH, has disclosed that he has received consulting fees and funds for research support from Bristol-Myers Squibb, Gilead Sciences, Janssen Therapeutics, Merck, and ViiV and funds for research support from AbbVie and Sangamo. Anton L. Pozniak, MD, FRCP, has disclosed that he has received consulting fees and funds for research support from Bristol-Myers Squibb, Gilead Sciences, Janssen Therapeutics, Merck, and ViiV.

4. clinicaloptions.com/hiv Highlights of IAS 2015 UNAIDS: 90-90-90 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 (%)

5. 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 (%)

6. clinicaloptions.com/hiv Highlights of IAS 2015 START: Immediate vs Deferred Therapy for Asymptomatic, ART-Naive Pts  International, randomized trial  Composite primary endpoint: any serious AIDS-related (AIDS-related death or AIDS- defining event) or non-AIDS–related event (non-AIDS–related death, CVD, end-stage renal disease, decompensated liver disease, non-AIDS–defining cancer)  Mean follow-up: 3 yrs; median baseline CD4+ cell count: 651 cells/mm 3 ; median baseline HIV-1 RNA: 12,759 copies/mL  Median CD4+ cell count at initiation of ART for deferred group: 408 cells/mm 3 Immediate ART ART initiated immediately following randomization (n = 2326) INSIGHT START Study Group. N Engl J Med. 2015;373:795-807. Lundgren J, et al. IAS 2015. Abstract MOSY0302. Deferred ART Deferred until CD4+ cell count ≤ 350 cells/mm 3, AIDS, or event requiring ART (n = 2359) HIV-positive, ART-naive adults with CD4+ cell count > 500 cells/mm 3 (N = 4685) Study closed by DSMB following interim analysis

7. clinicaloptions.com/hiv Highlights of IAS 2015 START: 57% Reduced Risk of Serious Events or Death With Immediate ART  4.1% vs 1.8% in deferred vs immediate arms experienced serious AIDS or non-AIDS–related event or death (HR: 0.43; 95% CI: 0.30-0.62; P <.001) 10 8 6 4 2 0 Cumulative Percent With Event 06121824303642485460 Mo Deferred ART Immediate ART INSIGHT START Group. N Engl J Med. 2015;373:795-807. Lundgren J, et al. IAS 2015. Abstract MOSY0302. Reproduced with permission.

8. clinicaloptions.com/hiv Highlights of IAS 2015 START: Primary Endpoint Components With Immediate vs Deferred ART Endpoint Immediate ART (n = 2326) Deferred ART (n = 2359) HR (95% CI) P Value NRate/100 PYN Serious AIDS-related event140.20500.720.28 (0.15-0.50)<.001 Serious non-AIDS–related event290.42470.670.61 (0.38-0.97).04 All-cause death120.17210.300.58 (0.28-1.17).13 Tuberculosis60.09200.280.29 (0.12-0.73).008 Kaposi’s sarcoma10.01110.160.09 (0.01-0.71).02 Malignant lymphoma30.04100.140.30 (0.08-1.10).07 Non-AIDS–defining cancer90.13180.260.50 (0.22-1.11).09 CVD120.17140.200.84 (0.39-1.81).65 INSIGHT START Group. N Engl J Med. 2015;373:795-807. Lundgren J, et al. IAS 2015. Abstract MOSY0302.

9. clinicaloptions.com/hiv Highlights of IAS 2015 START: Cancer Events With Immediate vs Deferred ART Cancer Event, n Immediate ART (n = 2326) Deferred ART (n = 2359) Total1439 Kaposi’s sarcoma111 Lymphoma, NHL + HL310 Prostate cancer23 Lung cancer22 Anal cancer12 Cervical or testis cancer 12 Other types*49 Time to Cancer Event 10 8 6 4 2 0 Cumulative % With Event 0 12 24 36 48 60 Mo *Immediate ART: squamous cell carcinoma, plasma cell myeloma, bladder cancer, fibrosarcoma. Deferred ART: gastric adenocarcinoma, breast cancer, ureteric cancer, malignant melanoma, myeloid leukemia, thyroid cancer, leiomyosarcoma, liver cancer, squamous cell carcinoma of head and neck. INSIGHT START Group. N Engl J Med. 2015;373:795-807. Lundgren J, et al. IAS 2015. Abstract MOSY0302. Reproduced with permission. Deferred ART Immediate ART Rate/100 PY: immediate, 0.20; deferred, 0.56 (HR: 0.36; 95% CI: 0.19-0.66; P =.001)

10. clinicaloptions.com/hiv Highlights of IAS 2015 START: Primary Endpoint Events by Latest CD4+ Cell Count Latest CD4+ count > 500 cells/mm 3 Immediate ART Deferred ART Primary events, % (n/N) 88 (37/42) 59 (57/96) Rate/100 PY 0.61.1 Immediate ARTDeferred ART Percent of Follow-up Time Latest CD4+ Cell Count (cells/mm 3 ) 60 50 40 30 20 10 0 2 (4.7) No. of Pts With Events (Rates/100 PY) 3 (0.8) 6 (0.4) 11 (0.6) 20 (0.6) 5 (1.8) 34 (2.0) 34 (1.5) 9 (0.6) 14 (1.1) < 350 350-499500-649 650-799≥ 800 < 350 350-499500-649650-799 ≥ 800 INSIGHT START Group. N Engl J Med. 2015;373:795-807. Lundgren J, et al. IAS 2015. Abstract MOSY0302. Reproduced with permission.

11. clinicaloptions.com/hiv Highlights of IAS 2015 TEMPRANO: Immediate or Deferred ART Initiation ± IPT for African Pts  Randomized, controlled, unblinded, multicenter (Ivory Coast), 2 x 2 factorial Pts with HIV infection and CD4+ cell count < 800 cells/mm 3 who did not meet WHO criteria for initiating ART* (N = 2056) Immediate ART † (n = 515) Immediate ART † + IPT ‡ (n = 518) Deferred ART § (n = 511) Deferred ART § + IPT ‡ (n = 512) *WHO criteria evolved during the study (updates 2006, 2010, 2013). † ART initiated immediately following randomization. ‡ IPT = 300 mg daily isoniazid initiated 1 mo after enrollment and terminated 7 mos after enrollment. § Deferred until meeting WHO criteria for initiating ART. TEMPRANO ANRS 12136 Study Group. N Engl J Med. 2015;373:808-822.  Pts in the treatment arms well matched at baseline –First-line ART primarily EFV + TDF/FTC (68% to 71%) or LPV/RTV + TDF/FTC (22% to 24%)  Median duration of follow-up: 29.9 mos

12. clinicaloptions.com/hiv Highlights of IAS 2015 TEMPRANO: Immediate vs Deferred ART Initiation and IPT Delivery for African Pts TEMPRANO ANRS 12136 Study Group. N Engl J Med. 2015;373:808-822. Mos From Randomization Cumulative Probability of Death or Severe HIV-Related Illness (%) 25 20 15 10 5 0 0612182430 Deferred ART Deferred ART + IPT Immediate ART Immediate ART + IPT 30-Mo Probability, % 14.1 8.8 7.4 5.7

13. 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.

14. 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--

15. clinicaloptions.com/hiv Highlights of IAS 2015  International, randomized, open-label phase II trial; results reported from Harlem, Bangkok, and Cape Town cohorts HPTN 067/ADAPT: PrEP Strategies Mannheimer S, et al. IAS 2015. Abstract MOAC0305LB. Holtz TH, et al. IAS 2015. Abstract MOAC0306LB. Bekker L, et al. CROI 2015. Abstract 978LB. Daily PrEP 1 dose daily Time-Driven PrEP † 1 dose twice weekly + 1 dose after sex HIV-negative MSM, TGW (Bangkok and Harlem*), and women (Cape Town) 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 0 66 47* † 52 * 100 80 60 40 20 Complete Coverage (%) Daily Time driven Event driven 85 84 74 ‡ 75 56 52 HPTN 067/ADAPT: Coverage of Sex Acts According to PrEP Strategy Mannheimer S, et al. IAS 2015. Abstract MOAC0305LB. Holtz TH, et al. IAS 2015. Abstract MOAC0306LB. Bekker L, et al. CROI 2015. Abstract 978LB. *P =.001 vs daily. † P =.47 vs event driven. ‡ P =.02 vs daily arm, P =.04 vs time-driven arm. § P <.001 comparing 3 arms. Complete coverage: taking ≥ 1 PrEP dose within 4 days before sex and ≥ 1 dose within 24 hrs after sex. Harlem Bangkok Cape Town §

17. clinicaloptions.com/hiv Highlights of IAS 2015 PrEP Demo: Implementation of Daily PrEP by US MSM/TGW  Prospective, open-label, cohort study conducted in 3 US STD or community- based clinics in San Francisco, Miami, and Washington, DC (N = 557) –Enrolled HIV-negative MSM (98%) and TGW (1.3%) who met behavioral risk criteria; participants offered daily TDF/FTC as PrEP for up to 48 wks  Retention rates declined from 93% at Mo 1 to 78% at Mo 12 –Participants with prior PrEP knowledge and those who reported condomless receptive anal sex at baseline had higher retention rates  63% of participants had protective TFV DBS levels at all study visits (consistent with ≥ 4 doses/wk) –Miami location, black race, fewer condomless anal sex partners, and unstable housing were factors associated with lower rates of protective TFV DBS levels  HIV incidence rates low at 0.43/100 PY (95% CI: 0.05-1.54) Liu A, et al. IAS 2015. Abstract TUAC0202.

18. clinicaloptions.com/hiv Highlights of IAS 2015 ATN 110: TDF/FTC PrEP For Young US MSM  Prospective, open-label, multicenter study Hosek S, et al. IAS 2015. Abstract TUAC0204LB. Behavioral Intervention HIV-negative 18- to 22-yr-old MSM at high risk for HIV contraction (N = 200) Wk 0: PrEP Dispensed TDF/FTC PrEP Wk 48  Baseline: mean age 20.2 yrs; 53% black, 21% white, 17% Latino, 7% other/mixed race, 2% Asian/pacific islander  4 seroconversions through Wk 48; each pt had undetectable TFV levels –HIV incidence: 3.29/100 PY –No drug resistance detected Behavioral intervention: Many Men, Many Voices (3MV) or Personalized Cognitive Counseling (PCC).

19. clinicaloptions.com/hiv Highlights of IAS 2015 ATN 110: Adherence to TDF/FTC PrEP in Young US MSM  Adherence decreased from baseline to Wk 48 –Undetectable levels of DBS TFV occurred in < 10% of pts at Wk 4 and ~ 30% of pts at Wk 48  Black pts had decreased adherence compared with other races Hosek S, et al. IAS 2015. Abstract TUAC0204LB. Reproduced with permission. 1200 1000 800 600 4+ doses 400 200 0 Levels of TFV in DBS (fmol/spot) 4 812243648 Overall White Latino Mixed Black 4+ doses Wks

20. clinicaloptions.com/hiv Highlights of IAS 2015  International, randomized, double-blind phase III trial  Pts generally well matched at baseline –Pts with HIV-1 RNA > 100,000 copies/mL: EVG/COBI/TDF/FTC arm, 24%; ATV/RTV + TDF/FTC arm, 25% WAVES: EVG/COBI/TDF/FTC vs ATV/RTV + TDF/FTC in Treatment-Naive Women Squires K, et al. IAS 2015. Abstract MOLBPE08. EVG/COBI/TDF/FTC QD + Placebos for ATV, RTV, and TDF/FTC QD (n = 289) ATV/RTV + TDF/FTC QD + Placebo for EVG/COBI/TDF/FTC QD (n = 286) HIV-infected women with HIV-1 RNA ≥ 500 copies/mL; no previous ART; and eGFR ≥ 70 mL/min (N = 575) Wk 48 Open- label extensio n ATV 300 mg; RTV 100 mg; TDF/FTC 300/200 mg; EVG/COBI/TDF/FTC 150/150/300/200 mg

21. clinicaloptions.com/hiv Highlights of IAS 2015 WAVES: Key Results  EVG/COBI/TDF/FTC superior to ATV/RTV + TDF/FTC –Overall treatment difference 6.5% (95% CI: 0.4% to 12.6%)  No significant differences between arms in change from BL for eGFR, spine or hip BMD, LDL or HDL cholesterol, total cholesterol to HDL ratio, or triglycerides  Significantly greater increase in total cholesterol with EVG/COBI/TDF/FTC  Lower rate of discontinuations due to AEs with EVG/COBI/TDF/FTC vs ATV/RTV + TDF/FTC (2.4% vs 7.0%) Squires K, et al. IAS 2015. Abstract MOLBPE08. Reproduced with permission. HIV-1 RNA < 50 c/mL (%) 100 80 60 40 20 0 Overall≤ 100,000> 100,000 HIV-1 RNA (copies/mL) EVG/COBI/TDF/FTC ATV/RTV + TDF/FTC 87 81 86 82 90 78 n = 2892862202146972 Emergent Resistance EVG/COBI/TDF/FTC (n = 289) ATV/RTV + TDF/FTC (n = 286) Resistance analysis population 1921 Developed resistance mutations to study drugs 03

22. 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.

23. 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.

24. clinicaloptions.com/hiv Highlights of IAS 2015  Randomized, active-controlled, open-label study  Primary endpoint: proportion of pts with HIV-1 RNA < 50 copies/mL after 48 wks of treatment GS-109: Switching From TDF- to TAF- Based Regimens in Suppressed Pts Mills A, et al. IAS 2015. Abstract TUAB0102. Pts with HIV-1 RNA 50 mL/min on stable TDF-based regimen for ≥ 48 wks (N = 1436) Switch to EVG/COBI/FTC/TAF QD* (n = 959) Continue previous TDF-based regimen † (n = 477) Primary Endpoint Wk 48 *EVG/COBI/FTC/TAF (150/150/200/10 mg). † Previous TDF-based regimens: EVG/COBI/FTC/TDF (n = 459), EFV/TDF/FTC (n = 376), ATV/(COBI or RTV) + TDF/FTC (n = 601). Continue through Wk 96

25. clinicaloptions.com/hiv Highlights of IAS 2015 GS-109: Virologic Outcomes Mills A, et al. IAS 2015. Abstract TUAB0102. Reproduced with permission. 100 80 60 40 20 0 Wk 48 HIV-1 RNA < 50 c/mL (%) All Prior Regimens Prior EFV/TDF/FTC Prior Boosted ATV + TDF/FTC Prior EVG/COBI/ FTC/TDF EVG/COBI/FTC/TAFTDF-based regimen Primary Endpoint P <.001 P =.02 P = NS 97 93 96 90 97 92 98 97 932/ 959 444/ 477 241/ 251 112/ 125 390/ 402 183/ 199 301/ 306 149/ 153 n/N =

26. clinicaloptions.com/hiv Highlights of IAS 2015 GS-109: Renal and Bone Outcomes  Hip BMD was similarly increased for pts treated with TAF regimen (P <.001) Mills A, et al. IAS 2015. Abstract TUAB0102. Reproduced with permission. Regimen Renal Events Leading to Discontinuation EVG/COBI/ FTC/TAF (n = 959)  Acute renal failure  Interstitial nephritis TDF-based regimen (n = 477)  Chronic kidney disease  Elevated serum creatinine  Fanconi syndrome (mild jaundice)  Increased creatinine  Nephritic colic (nephrolithiasis) 4 3 2 1 0 -2 -3 Median % Change in Spine BMD (Q1, Q3) BaselineWk 24 EVG/COBI/FTC/TAF TDF-based regimen Wk 48 1.79 -0.28 P <.001

27. clinicaloptions.com/hiv Highlights of IAS 2015 Switching Pts With HIV/HBV Coinfection to a TAF-Based Regimen  By Wk 48, 2/70 (3%) pts lost HBsAg/gained HBsAb; 2/30 (7%) pts had lost HBeAg; 1/30 (3%) pts gained HBeAb  Significant improvement in median Wk 48 FibroTest score with switch (-.04; P =.018) Gallant J, et al. IAS 2015. Abstract WELBPE13. Reproduced with permission. Pts (%) 94 92 Wk 24 Wk 48 100 80 60 40 20 0 HBV DNA < 29 IU/mL 86 92  International, multicenter, single-arm, open-label phase IIIb trial (N = 72) –Pts with virologically suppressed HIV infection on any regimen, chronic HBV coinfection, and eGFR > 50 mL/min switched to EVG/COBI/FTC/TAF for 48 Wks HIV-1 RNA < 50 c/mL 100 80 60 40 20 0

28. clinicaloptions.com/hiv Highlights of IAS 2015  Multicenter, open-label phase III trial GS-112: Switching to a TAF-Based Regimen in Pts With Renal Impairment Gupta S, et al. IAS 2015. Abstract TUAB0103. Virologically suppressed, HIV-positive pts with mild-moderate renal impairment (stable eGFR CG [30-69 mL/min]) (N = 242) TDF-Based ART (n = 158) Non-TDF–Based ART (n = 84) EVG/COBI/FTC/TAF (N = 242) Wk 96 PINNRTIINSTI CCR5 Antag. TDFABC Other NRTI No NRTI ART use,%4442243652275 Wk 48Wk 24

29. clinicaloptions.com/hiv Highlights of IAS 2015 GS-112: Key Results Change in eGFR From Baseline to Wk 48 Changes in Spinal BMD From Baseline to Wk 48 Gupta S, et al. IAS 2015. Abstract TUAB0103. Reproduced with permission. TDFNon-TDF Median Change From Baseline 10 0 -10 +0.2 -1.8 -1.5 -2.7* Baseline:58535650 eGFR CG mL/min eGFR CKD-EPI Cr mL/min/1.73 m 2 *P <.05 TDFNon-TDF *P <.05 4 2 0 -2 Mean % Change Spine BMD 2.95* 0.99 Baseline Wk 24 Wk 48

30. clinicaloptions.com/hiv Highlights of IAS 2015 P007: DOR + TDF/FTC vs EFV + TDF/FTC in ART-Naive Pts Infected With HIV  Double-blind, randomized, 2-part study Gatell JM, et al. IAS 2015. Abstract TUAB0104. ART-naive, HIV-positive pts with HIV-1 RNA ≥ 1000 copies/mL and CD4+ cell count ≥ 100 cells/mm 3 (N = 216*) Doravirine † + TDF/FTC (n = 108) Efavirenz ‡ + TDF/FTC* (n = 108) *Combined pts from 2 study parts: Part 1 was a dose-finding study (n = 84) and Part 2 enrolled additional pts with the current dosing schema (n = 132). † Doravirine dosed at 100 mg QD. ‡ Efavirenz dosed at 600 mg QD. § Wk 24 results reported. Pts were stratified by HIV-1 RNA ≤ or > 100,000 copies/mL Wk 96 §

31. clinicaloptions.com/hiv Highlights of IAS 2015 P007: Key Results  Most virologic failure was due to low-level viremia –Virologic failure, HIV-1 RNA ≥ 40 copies/mL: DOR, 15.7%; EFV, 10.2% –Virologic failure, HIV-1 RNA ≥ 200 copies/mL: DOR, 3.7%; EFV, 0.9%  Resistance testing was performed in 1 pt in each arm who failed treatment; no NRTI or NNRTI mutations detected Gatell JM, et al. IAS 2015. Abstract TUAB0104. Pts With HIV-1 RNA < 40 c/mL, %* DOR + TDF/FTC (n = 108) EFV + TDF/FTC (n = 108) Wk 827.826.9 Wk 1663.657.5 Wk 2472.273.1 Baseline HIV-1 RNA ≤ 100,000 c/mL (n/N) † 83.3 (55/66) 85.7 (54/63) Baseline HIV-1 RNA > 100,000 c/mL (n/N) † 60.5 (23/38) 65.8 (25/38) *NC = F approach. † Observed failure approach. Event, % DOR + TDF/FTC (N = 108) EFV + TDF/FTC (N = 108) One or more AE75.984.3 Serious AE0.94.6 Discontinued due to AE 0.95.6 Drug-related AE27.855.6 Pts with ≥ 1 CNS event 26.946.3

32. clinicaloptions.com/hiv Highlights of IAS 2015  Prospective, observational study Comparison of Single- and Multiple-Tablet Regimens in ART-Naive Pts Gatell JM, et al. IAS 2015. Abstract TUPEB264. EFV/TDF/FTC Single-Tablet Regimen (n = 759) EFV + TDF + FTC Multitablet Regimen* (n = 483) Other Multitablet Regimen (n = 1531) ART-naive pts assigned at physician’s discretion to the noted regimens (N = 2773) Baseline CharacteristicsEFV/TDF/FTC STREFV/TDF/FTC MTROther MTR Age, media (IQR)37 (31-44) 37 (30-44) Male, %898481 Median CD4+ cells/mm 3 (IQR)328 (225-446)274 (175-381)300 (179-415) Median HIV-1 RNA copies/mL375212511827692 Median duration of regimen, yrs (IQR)2.5 (1-3.6)0.7 (0.2-1.8)1.7 (0.7-2.5) *Regimen could consist of single components (EFV + TDF + FTC) or EFV + coformulated TDF/FTC.

33. clinicaloptions.com/hiv Highlights of IAS 2015 Single- vs Multiple-Tablet Regimens in ART-Naive Pts: Efficacy and Cost Gatell JM, et al. IAS 2015. Abstract TUPEB264. Response,* % ART Cost, Euros Initiation Cost, Euros Cost/Responder,* Euros Ratio EFV/TDF/FTC STR 79 (n = 759) 7370941412,0181 EFV + TDF + FTC MTR 64 (n = 483) 6736819812,6511.04 Other MTR 64 (n = 1531) 835011,38017,7331.47 *At 48 wks.

34. clinicaloptions.com/hiv Highlights of IAS 2015  Randomized, multipart phase IIa trial AI468002: BMS-955176 + ATV ± RTV for Treating Pts Infected With HIV Hwang C, et al. IAS 2015. Abstract TUAB0106LB. HIV, subtype B–infected PI- and MI-naive pts with HIV-1 RNA ≥ 5000 c/mL and CD4+ cell count ≥ 200 cells/mm 3 (N = 28) BMS-955176 40 mg QD + ATV 300 mg QD + RTV 100 mg QD (n = 8) BMS-955176 40 mg QD + ATV 400 mg QD (n = 8) BMS-955176 80 mg QD + ATV 400 mg QD (n = 8) Day 28* *Followed to Day 42. BMS-955176 prevents viral maturation by inhibiting cleavage between p24 and Gag SP1. ATV 300 mg QD + RTV 100 mg QD + TDF 300 mg QD/FTC 200 mg QD (n = 4) Max. Median Decline in HIV-1 RNA from BL through Day 42 (log 10 c/mL) -2.02 -1.86 -2.23 -2.39  No serious AEs or discontinuations for AEs –1 grade 3/4 Tx-related AE in BMS-955176 80 mg + ATV 400 mg arm (transient neutropenia)

35. clinicaloptions.com/hiv Highlights of IAS 2015 Long-term BMD Changes in HIV-Infected, ART-Treated Pts  Case-controlled, observational cohort study  Assessed HIV-positive pts who had baseline and follow-up DXA measurements during the A5202/A5224s study and another DXA measurement during ACTG A5318 trial (n = 97) –A5224s study: treatment-naive pts randomized to ATV/RTV, EFV + TDF/FTC, or ABC/3TC –Control cases derived from 2 cohorts comprising HIV-uninfected individuals (n = 614)  Key baseline characteristics, HIV-infected pts –Median cumulative TDF use: 5.8 yrs (range: 1.1-7.4) –Median cumulative PI use: 3.7 yrs (range: 0-7.4) Grant P, et al. IAS 2015. Abstract TUPDB0103.

36. clinicaloptions.com/hiv Highlights of IAS 2015 Long-term BMD Changes in HIV-Infected, ART-Treated Pts  0 to Wk 96: BMD loss at lumbar spine and hip significantly greater in HIV-infected vs uninfected pts (P <.001) –Multivariate analysis, HIV-infected pts: BMD loss associated with lower CD4+ cell count (lumbar spine only), higher HIV-1 RNA, TDF use  Wk 96 to final: HIV infection associated with significantly greater BMD loss at lumbar spine (P =.012) but not at hip (P =.99) –Multivariate analysis, HIV-infected pts: BMD loss associated with total lean body mass Grant P, et al. IAS 2015. Abstract TUPDB0103. Reproduced with permission. Change in Lumbar Spine BMD by Serostatus HIV- HIV+ L1L4 BMD Change (%) 0 -2 -4 0244896144192360 Wks Change in Total Hip BMD by Serostatus HIV- HIV+ Total Hip BMD Change (%) 0 -4 -5 0244896144192360 Wks -2 -3

37. clinicaloptions.com/hiv Highlights of IAS 2015  Randomized, controlled, open-label phase IV study MIDAS: Metabolic Effects of Switching From EFV/TDF/FTC to DRV/RTV Hamzah L, et al. IAS 2015. Abstract TUPDB0102. Switch to DRV/RTV 800/100 mg QD monotherapy (n = 32) HIV-infected pts with HIV-1 RNA 6 mos (N = 64*) Continue EFV/TDF/FTC (n = 32) Wk 48  At baseline, the median time on EFV/TDF/FTC was 3.5 yrs (IQR: 2.5-3.9) *70 pts were randomized; 64 were available for analysis.

38. clinicaloptions.com/hiv Highlights of IAS 2015 MIDAS: Key Results  4 cases of virologic failure reported in DRV/RTV arm (12.5%) –Virologic rebound (n = 3), CNS escape (n = 1)  No significant change in renal parameters Hamzah L, et al. IAS 2015. Abstract TUPDB0102. Reproduced with permission. DRV/RTV EFV/TDF/FTC P =.03 Mean Change, Total Hip BMD (%) Weeks 3 2 1 0 -2 048 10.0 5.0 0 -5.0 -10.0 -15.0 Mean Unadjusted Difference at Wk 48 25(OH)D1,25(OH)2D EFV/TDF/FTC DRV/RTV -3.5 -16.6 4.8 0.9 Change in Vitamin D Parameters, Wk 48

39. clinicaloptions.com/hiv Highlights of IAS 2015 ION-4: LDV/SOF for 12 Wks in GT1/4 HIV/HCV-Coinfected Pts  Open-label, single-arm phase III study  98% infected with GT1 HCV, 20% cirrhotic, 34% black  No efficacy differences among most subgroups, including prior HCV treatment and presence of cirrhosis –SVR12 rates significantly lower in black vs nonblack pts (90% vs 99%, P <.001); differences noted across ART regimens; this is not observed in HIV-negative pts  HIV disease remained stable during LDV/SOF: CD4+ cell counts remained stable through treatment, follow-up; no confirmed HIV-1 virologic rebound noted  Regimen well tolerated, with no treatment discontinuations due to toxicity Ledipasvir/Sofosbuvir QD Pts with suppressed HIV infection (HIV-1 RNA < 50 copies/mL) and GT1/4/6 HCV coinfection (N = 335) Wk 12 SVR12, % 96 Cooper C, et al. IAS 2015. Abstract TUAB0202. Naggie S, et al. N Engl J Med. 2015;373:705-713. Afdhal N, et al. N Engl J Med. 2014;370:1889-1898.

40. clinicaloptions.com/hiv Highlights of IAS 2015 C-EDGE Coinfection: Grazoprevir/Elbasvir for Pts Coinfected With HIV/HCV  Multicenter, single-arm, open-label phase III trial Grazoprevir/Elbasvir HCV NS3/4A inhibitor/HCV NS5A inhibitor HCV treatment-naive pts coinfected with HIV and GT1, 4, or 6 HCV; stable on ART ≥ 8 wks (N = 218) Wk 12 Coformulation dosed orally 100/50 mg QD Baseline ART Characteristic, %Grazoprevir/Elbasvir (N = 218) Undetectable HIV-1 RNA on ART96.8 ART regimen  Abacavir containing21.6  TDF containing75.2  Raltegravir51.8  Dolutegravir27.1  Rilpivirine17.4 Rockstroh JK, et al. IAS 2015. Abstract TUAB0206LB. Rockstroh JK, et al. Lancet HIV. 2015;2:e319-e327.  66% GT1a HCV, 60% had HCV RNA > 800,000 IU/mL, 16% cirrhotic

41. clinicaloptions.com/hiv Highlights of IAS 2015 0 100 80 60 20 C-EDGE Coinfection: Key Findings  No subgroup provided efficacy advantage or disadvantage, including ART regimen  New NS3, NS5A RAVs detected at failure in 4 of 5 pts who relapsed  Short-lived HIV-1 RNA increases in 2 pts on ART during GZR/EBV treatment –Both resuppressed HIV-1 RNA without change of ART  During GZR/EBV Tx, no significant changes in CD4+ cell count  GZR/EBV well tolerated: no pt discontinued for AEs and no serious treatment-related AEs SVR12 (%) 139/ 144 42/ 44 27/ 28 All PtsGT1aGT1bGT4 96.3 96.5 95.5 96.4 210/ 218 SVR12 With 12 Wks GZR/EBV According to Genotype Discontinued*1010 Relapse5401 Reinfection2110 *Unrelated to virologic failure. n/N = 40 Rockstroh JK, et al. IAS 2015. Abstract TUAB0206LB. Rockstroh JK, et al. Lancet HIV. 2015;2:e319-e327. Reproduced with permission.

42. clinicaloptions.com/hiv Highlights of IAS 2015  Mother’s history –Treated with zalcitabine from 13 wks gestation to delivery –At delivery, HIV-1 RNA level 4.63 million copies/mL; CD4+ cell count 81 cells/mm 3  Pt’s history –ZDV initiated in female pt at birth; HIV-1 RNA undetectable Day 3; HIV-1 DNA undetectable Days 3 and 14, but detectable at Wk 4 –ZDV interrupted Wk 6; HIV-1 RNA level at Mo 3: 2.17 million copies/mL; ART initiated (ZDV + ddI + 3TC + RTV) –LTFU between 5.8 and 6.8 yrs; ART interrupted –Undetectable HIV-1 RNA level upon return; no further ART since (currently 18 yrs of age)  HIV-1 RNA in pt remained < 50 copies/mL from 6.8-18.3 yrs of age except for 1 increase at 12 yrs of age (510 copies/mL)  Low levels of replicating virus detected after in vitro stimulation of purified CD4+ T cells Sustained Remission > 12 Yrs After Interrupted ART in Perinatally Infected Pt Sáez-Cirión A, et al. IAS 2015. Abstract MOAA0105LB.