J-M Molina 1 *, A LaMarca 2 , J Andrade-Villaneuva 3 , B Clotet 4 ,

1. Elvitegravir Once Daily is Non-Inferior to Raltegravir Twice Daily in Treatment- Experienced Patients: 48 Week Results From a Phase 3 Multicenter, Randomized Double-Blind Study J-M Molina1*, A LaMarca2, J Andrade-Villaneuva3, B Clotet4, N Clumeck5, Y-P Liu6, L Zhong6, N Margot6, A Cheng6, J Szwarcberg6 and SL Chuck6 1Hopital Saint Louis and Univ. Paris 7 Diderot, Paris, France; 2Therafirst Medical Center, Ft Lauderdale, FL; 3Hospital Civil de Guadalajara, CUCS, U de G, Guadalajara, Mexico; 4Hospital Universitario Germans Trias i Pujol, Barcelona, Spain; 5C.H.U. St. Pierre, Brussels, Belgium; 6Gilead Sciences, Foster City, CA, USA 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention 20 July 2011 Paper # WELBB05

2. Study Design 183-0145 • 96-week randomized (1:1), double-blind, double-dummy • Treatment-experienced patients • Background regimen (BR) based on resistance testing: • 2nd Agent: fully active PI/r • 3rd Agent: NRTI, ETR, MVC, T-20 • If M184V/I, may add 3TC or FTC • Primary Endpoint: HIV-1 RNA < 50 copies/mL through 48 weeks (FDA TLOVR) • Non Inferiority Study with lower limit 95% CI at -10% (n = 702)

3. Baseline Characteristics

4. Subject Disposition through Week 48 Screened (n=1335) Screen Failure (n=603) Not Randomized (n=8) Randomized (n=724) Not Treated (n=7) Not Treated (n=5) EVG (n=354) RAL (n=358) GCP violation (n=3) GCP violation (n=7) EVG (n=351) RAL (n=351) 76% on EVG at W48 (n=266) 24% not on EVG at W48 (n=85) 24% not on RAL at W48 (n=83) 76% on RAL at W48 (n=268)

5. Selected Background Regimens PI/r 3rd Agent NRTI 3rd Agent Etravirine 13% Maraviroc 6% FTC/TDF 27% Other* 1% Lamivudine 4% Abacavir 3% Tenfovir DF 59% Other^ 7% NRTI only 80% *Other: T-20, T-20+TDF, ETR+NRTI ^Other: 3TC/ABC, 3TC/ZDV, Zidovudine, Didanosine, Emtricitabine Patients on 3 or more drugs were allowed if M184VI mutation present.

6. Primary Endpoint ITTTLOVR Week 48 HIV-1 RNA <50 copies/mL *p=0.001 for non-inferiority 1 Responder: achieved and maintained confirmed HIV-1 RNA <50 copies/mL through Week 48 2 Drug DC due to Other: Lack of Efficacy, Lost to Follow-up, Non-compliance, Investigator Discretion, Pregnancy, Protocol Violation, Withdrew Consent

7. Mean Change from Baseline in CD4 (cells/mm3) 200 150 100 50 0 EVGRAL 147 138 Change from Baseline in CD4 (cells/mm3) Weeks on Study BL 2 4 8 12 16 20 24 32 40 48 EVGRAL 340 321 313 317 309 301 293 293 284 273 341 311 322 322 313 314 300 302 259 290

8. Resistance Development by Week 48In Subjects with Virologic Failure* • Virologic Failure:subjects who experience either suboptimal virologic response (two consecutive visits with HIV-1 RNA ≥50 c/mL and <1 log10 below baseline at week 8), virologic rebound (two consecutive visits with HIV-1 RNA either ≥400 c/mL after achieving HIV-1 RNA <50, or >1 log10 increase from nadir), or had HIV-1 RNA ≥400 c/mL at their last visit. • 1 Integrase inhibitor resistance mutations: T66I/A/K, E92Q/G, T97A, Y143R/H/C, S147G, Q148H/K/R, and N155H/S in integrase.

9. Adverse Events

10. Adverse Events Grades 2-4* *≥ 3% of subjects in either group ^p-value=0.023

11. Laboratory Abnormalities – Grade 3-4* *>5 subjects in any treatment group ^p-value= 0.039; †p-value = 0.020;#p-value = 0.009

12. Conclusions • In the first Phase 3 comparative integrase inhibitor study, Elvitegravir QD is non-inferior to Raltegravir BID, when given with a fully active boosted protease inhibitor • In patients with virologic failure, a minority (~20%) developed integrase resistance • Elvitegravir was well tolerated, with a safety profile comparable to Raltegravir • Elvitegravir is currently being evaluated in two ongoing Phase 3 treatment-naïve studies as a component of the Quad single-tablet regimen

13. Investigators United States/Puerto Rico K. Abriola B. Akil B. Barnett T. Barrett N. Bellos D. BergerG. Blick R. Bolan I. Brar F. Bredeek C. Brinson J. Burack L. Bush R. Campo D. Chew P. Cimoch C. Cohen P. Cook R. Corales D. Coulston C. CreticosG. Crofoot F. Cruickshank E. DeJesus S. Diamond R. Dretler H. Edelstein R. Elion T. File D. FishJ. Flamm F. Garcia J. Gathe, Jr. R. Greenberg P. Greiger-Zanlungo D. Hagins T. Hawkins C. Hicks J. Horton R. Hsu G. Huhn T. Jefferson D. Kaufman H. Khanlou C. Kinder R. Kuhn A. LaMarca H. LampirisM. Lee R. Liporace C. Lucasti R. MacArthur C. Martorell C. Mayer M. McKellarD. Mildvan A. Mills J. Morales-Ramirez K. Mounzer R. Myers, Jr. R. Nahass E. Turner Overton G. Pierone M. Ramgopal J. Ravishankar K. Rawlings G. Richmond W. Robbins A. Roberts J. Rodriguez P. Ruane S. Saavedra J. Santana Bagur L. Santiago A. Scarsella S. Schrader A. Scribner M. Sension G. Sepulveda-Arzola D. Shamblaw K. Stazskow J. Stephens C. Shikuma J. Slim L. Sloan P. Tebas M. Thompson J. Timpone W. Towner L. WaldmanD. Wheeler A. WilkinS. Pegram M. Wohlfeiler K. Workowski B. Zingman

14. Investigators Australia D. Baker M. Bloch D. Cooper D. Dwyer R. Garsia P. Konecny D. Smith C. Workman BelgiumN. Clumeck E..Florence J. Goffard J. Legrand M. Moutschen CanadaB. Chang B. Conway L. Johnston F. LaPlante R. LeBlanc K. Logue D. Murphy A. Rachlis S. Walmsley FranceJ. Durant P-M Girard C. Katlama B. Marchou J-M Molina J-L Pellegrin L. Slama F. Raffi P. Yeni GermanyS. Esser G. Fätkenheuer H. August Horst H. Jäger A. Plettenberg S. Reuter C. Stephan J. van Lunzen ItalyA. Antinori M. Galli A. Lazzarin F. Maggiolo G. Rizzardini V. Vullo MexicoJ. Andrade Villanueva M. Magaña L. Mosqueda J. Sierra NetherlandsB. Rjinders PortugalF. Antunes T. Branco A. Diniz R. SerrãoR. Marques E. Teofilo SpainJR. Arribas J. Berenguer B. Clotet P. Domingo J. Maria Gatell J. Luis Gómez Sirvent F. Gutiérrez J. Hernández Quero M. Márquez S. Moreno J. Portilla F. Pulido P. Viciana United KingdomC. Leen E. Wilkins I. Williams A. Winston