Joel E. Gallant, MD, MPH Medical Director, Specialty Services Southwest CARE Center Santa Fe, New Mexico State-of-the-ART in Antiretroviral Management FORMATTED: MM/DD/YY New Orleans, Louisiana: December 15-17, 2015

START: 57% Reduced Risk of Serious Events or Death With Immediate ART  1.8% vs 4.1% in deferred vs immediate arms experienced serious AIDS or non-AIDS related event or death: HR = 0.43 (95% CI: 0.30 to 0.62); P < Cumulative Percent With Event Month Deferred ART Immediate ART Lundgren J, et al. N Engl J Med Slide 6 of 38

GS104/111: Smaller decline in hip and spine BMD with TAF  Smaller decline in hip and spine BMD with TAF Wk =845 = P <.001 Mean % Change From BL Sax P, et al. CROI Abstract 143. n TAF/FTC/EVG/COBI (n = 866) TDF/FTC/EVG/COBI (n = 867) Slide 17 of 38

GS 104/111: TAF vs. TDF: Quantitative Proteinuria Median % Change from Baseline (Q1, Q3) Protein (UPCR) Albumin (UACR) RBP Beta2- microglobulin p <0.001 for all Urine [protein]:Creatinine Ratio E/C/F/TAF E/C/F/TDF Baseline 44 mg/g 44 mg/g 5 mg/g 5 mg/g 64 μg/g 67 μg/g 101 μg/g 103 μg/g Sax P, et al. 22nd CROI; Seattle, WA; February 23-26, Abst. 143LB. Protein (UPCR) Albumin (UACR) RBP Slide 19 of 38

GS-109: Switch from TDF-based Regimens to E/C/F/TAF: Renal and Bone Outcomes Hip BMD was similarly increased for pts treated with TAF regimen Mills A, et al. IAS Abstract TUAB0102. 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  Nephretic colic (nephrolithiasis) Median % Change in BMD (Q1, Q3) BaselineWeek 24 EVG/COBI/FTC/TAF TDF-Based Regimen Week P <.001 Slide 23 of 38

GS-112: Switching to E/C/F/TAF Regimen With Renal Impairment (eGFR 30-60) Changes in eGFR to Wk 48 Changes in spinal BMD to Wk 48 Gupta S, et al. IAS Abstract TUAB0103. Total TDF Non-TDF Median Change from Baseline * * Baseline: eGFR CG mL/min eGFR CKD-EPI Cr mL/min/1.73m 2 *P < TotalTDFNon-TDF *P < Mean % Change Spine BMD 2.95* 2.29* 0.99 Multicenter, open-label phase III trial, N=242 (158 on TDF, 84 on non-TDF-based regimen) Slide 24 of 38

GS 119: Virologic Suppression After Switch to EVG/COBI/FTC/TAF + DRV Similar rates of maintained virologic suppression at Wk 24, but significantly higher rates with switch vs baseline ART at Wk 48 Huhn S, et al. ID Week Abstract 726. Week 24 VL< 50 Virologic Failure No Data EVG/COBI/FTC/TAF + DRV Baseline ART Patients (%) Week 48 VL < 50 Virologic Failure No Data Treatment difference: 5.3% (95% CI: -3.4 to 17.4; P =.23) Treatment difference: 18.3% (95% CI: 3.5 to 33; P =.004) Slide 26 of 38

5 2 STRIIVING: Virologic Outcomes at Wk 24  Switch to DTG/ABC/3TC noninferior to maintaining baseline ART  No cases of protocol-defined virologic failure –3 pts in DTG/ABC/3TC arm (1%) and 4 pts in BL ART arm (1%) had VL > 50 but < 100 through Wk 24 Trottier B, et al. ICAAC Primary Efficacy Analysis: ITT-Exposed and Per Protocol Populations Virologic Success Virologic Nonresponse No Virologic Data HIV-1 RNA < 50 c/mL (%) DTG/ABC/3TC (ITT-E, n = 274) Baseline ART (ITT-E, n = 277) DTG/ABC/3TC (PP, n = 220) Baseline ART (PP, n = 215) < ITT-E Population PP Population -3.4 DTG/ABC/3TCBaseline ART Slide 29 of 38

PADDLE: All Pts Virologically Suppressed by Wk 8 of DTG + 3TC  Included 4 pts with VL > 100,000 at BL Figueroa MI, et al. EACS Abstract Pt # HIV-1 RNA (copies/mL) ScreenBLDay 2Day 4Day 7Day 10Wk 2Wk 3Wk 4Wk 6Wk 8Wk 12Wk , < , < ,335151,56937, < ,291148,37011, < ,36220, < ,02414, < ,60418, < ,07124, Not done268105< ,70710,832Not done516202< , < ,089273,676160,97468, < ,50864, < ,09333,82937,35026, < ,34815, < < ,18523,50015, < 50 Not done< , < ,10025,82811, < ,77173,06931, < ,803106,32035, < < 50 Slide 32 of 38

LATTE: Virologic Success Through Maintenance Week 96  6 pts in CAB arms with PDVF at Wk 96; 4 additional pts since Wk 48 Margolis D, et al. CROI Abstract 554LB. VL < 50 c/mL by Snapshot Algorithm (%) BL Induction PhaseMaintenance Phase CAB 10 mg (n = 60) CAB 30 mg (n = 60)* CAB 60 mg (n = 61) EFV 600 mg (n = 62) 68% 63% 84% 75% Wks *Cabotegravir 30 mg selected for future development Slide 33 of 38

Recent Switch Studies: Suppressed Patients TrialFromToOutcome GS-123 TDF/FTC + RALEVG/COBI/FTC/TDF ✔ GS-264 TDF/FTC/EFVRPV/FTC/TDF ✔ Strategy-NNRTI TDF/FTC + NNRTIEVG/COBI/FTC/TDF ✔ Strategy-PI TDF/FTC + PI/rEVG/COBI/FTC/TDF ✔ SPIRIT 2 NRTI + PI/rRPV/FTC/TDF ✔ SPIRAL 2 NRTI + PI/r (exp’d pts)2 NRTI + RAL ✔ SALT ATV/r + 2 NRTIATV/r + 3TC ✔ OLE LPV/r + 2 NRTIsLPV/r + 3TC ✔ GS-109 TDF-based ARTEVG/COBI/FTC/TAF ✔ STRIIVING Suppressive ARTDTG/ABC/3TC ✔ ATLAS-M ATV/r + 2 NRTIsATV/r + 3TC ✔ GS-119 “Salvage regimen” (exp’d pts)EVG/COBI/FTC/TAF + DRV ✔ LATTE CAB or EFV + 2 NRTIsCAB + RPV ✔ SWITHCMRK 2 NRTI + LPV/r (exp’d pts)2 NRTI + RAL ✗ MARCH 2 NRTI + PI/rPI/r + MVC ✗ HARNESS 2 NRTI + 3 rd AgentATV/r + RAL ✗ Adapted from David Wohl Slide 34 of 38