The 48th Interscience Conference on Antimicrobial Agents and Chemotherapy and 46th Infectious Disease Society of America Meeting Washington, DC October 24-28, 2008 and 9 th International Congress on Drug Therapy in HIV Infection Glasgow, Scotland November 9-13, 2008

When to Start

NA-ACCORD: Improved Survival When ART is Started with ≥350 CD4 ● North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) ○ Regional collaboration of 22 HIV research cohorts from United States and Canada ● Study patients: All HIV-infected individuals with CD4 count of cells/mm 3 while in active follow-up between 1996 and 2006 ● Outcome: All-cause mortality ● Groups compared from same CD4 count level: ○ Immediate treatment: Initiate ART within 1.5 yrs after 1st CD4 count between cells/mm 3 ○ Deferred treatment: Do not initiate ART in this time frame ● Patients censored when not initiating within the 1.5 year interval after their target CD4 count for ART initiation Kitahata M, et al. 48 th ICAAC/46 th IDSA; Washington, DC; October Abst. H-896b

NA-ACCORD: Baseline Characteristics Initiate HAART (n=2,473) Defer HAART (n=5,901) Follow up person-years8,35816,636 Males (%)8375 Median Age (years)4038 White (%)3938 Median CD4 count cells/mm Median log 10 HIV RNA copies/mL Hepatitis C virus infection (%)2734 History of Injection Drug Use (%)1621 Kitahata M, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-896b

NA-ACCORD: Results Relative Hazard (RH)* 95% Confidence Interval P-value Deferral of HAART at cells/mm , 2.1<0.001 Female Sex1.10.9, Older Age (per 10 years)1.61.5, 1.8<0.001 Baseline CD4 count (per 100 cells/mm 3 ) , ● HIV RNA was not an independent predictor of mortality ● Rate of virologic suppression (<500 c/ml) similar between groups Kitahata M, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-896b *Stratified by Cohort and Year

What to Start

STARTMRK: Raltegravir vs Efavirenz ● HIV RNA >5000 c/mL ● Susceptible to EFV, TDF and FTC Randomized (1:1), double blind, study ART-naïve subjects (N=561) RAL (400 mg BID) + TDF/FTC QD + EFV Placebo EFV (600 mg QHS) + TDF/FTC QD + RAL Placebo Lennox J, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-896a

STARTMRK: Baseline Characteristics RAL + TDF/FTC (n=281) EFV + TDF/FTC (n=282) Age (mean, years)3837 % Male8182 % Non-White5956 vRNA copies/mL (geometric mean) 103,205106,215 % with vRNA >10 5 copies/mL5551 Mean CD4 count (cells/μl) % with CD4 ≤200 cells/μl4748 % Hepatitis B or C77 % Non-Clade B2117 Lennox J, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-896a

STARTMRK: Results Lennox J, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-896a

STARTMRK: Results ● Time to virologic suppression faster with RAL (P<0.001) ● Virologic failures similar ○ RAL 12 (4 with RAL, 3 with FTC resistance) ○ EFV 8 (3 with EFV, 1 with FTC resistance) ● Lower incidence of drug-related adverse events with RAL ○ Overall: RAL 44% vs EFV 77% (P<0.001) ○ CNS at week 8: RAL 10.3% vs 17.7% (P=0.015) – persisted through week 48 Lennox J, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-896a

STARTMRK: Fasting Serum Lipid Changes from Baseline to Week 48 Mean Change (mg/dL) P<0.001 Lennox J, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-896a

ARTEMIS: Phase III Study Design 96 Week Results Presented DRV/r 800/100mg QD + TDF/FTC (n=343) LPV/r* 400/100mg BID or 800/200mg QD + TDF/FTC (n=346) 689 ARV-naïve patients VL>5,000 *Dosing was based on regulatory approval; switch was made according to local regulatory approval and drug availability. LPV/r BID 75%; Capsule/tablet switch 86% Mills A, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1250c

ARTEMIS: Baseline Characteristics DRV/r + TDF/FTC QD (n=343) LPV/r + TDF/FTC QD (n=267) Baseline demographics Female, N (%) 104 (30)105 (30) Caucasian 40%44% Baseline disease characteristics Median HIV-1 RNA (c/mL) 70,80062,100 Median CD4 (cells/mm 3 ) HBV/HCV co-infected 13%14% Stratification factors at screening CD4 count <200 cells/mm 3 41%43% Plasma HIV-1 RNA ≥100,000 c/mL 34%35% Mills A, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1250c

ARTEMIS: HIV RNA <50 c/mL to Week 96 (TLOVR) P=0.024 Percent HIV RNA <50 c/mL *Estimated difference in response vs LPV/r for non-inferiority: PP = 8.4% (95% CI 1.9;14.8, P<0.001) *Estimated difference in response vs LPV/r for superiority: ITT = 8.3% (95% CI 1.8;14.7, P=0.012) Mills A, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1250c

ARTEMIS: Response by VL and CD4 Strata and Adverse Events ● Higher rate of GI adverse events in LPV/r arm (Diarrhea 4% vs. 11%, P<0.001) ● Grade 2-4 increases in total cholesterol (18% vs. 28%, P=0.0016) and triglycerides (4% vs. 13%, P<0.0001) higher in LPV/r arm DRV/r + TDF/FTCLPV/r + TDF/FTC ≥100, <100,000 Baseline viral load (copies/mL) % HIV RNA <50 copies/mL (ITT-TLOVR) 63 P=0.023 n = P= ≥ <200 Baseline CD4 cell count (cells/mm 3 ) n= P=0.009P= Mills A, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1250c

ARTEMIS: Median Increase in Lipid Levels at Week LPV/r + TDF/FTC DRV/r + TDF/FTC Total cholesterol LDLc cholesterol HDL cholesterol Triglycerides Median increase in concentration (mg/dL) Mills A, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1250c 50 60

ATV/r 300/100 mg QD + TDF/FTC QD (n=440) CASTLE: Study Design (1:1) International, multicenter, open-label, randomized, 96-week study to determine the comparative clinical efficacy and safety of ATV/r and LPV/r in treatment-naïve HIV-1 infected subjects HIV RNA  5000 c/mL, no CD4 cell count restriction Stratified by HIV RNA <100,000 c/mL vs  100,000 c/mL and geographic region LPV/r 400/100 mg BID + TDF/FTC QD (n=443) Molina J, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1250d

CASTLE: Baseline Characteristics ATV/r + TDF/FTC (n=440) LPV/r + TDF/FTC (n=443) Median Age (years) 3436 Female (%) 31 CDC Class C (%) 45 HIV RNA median (log 10 c/mL) HIV RNA ≥100,000 c/mL (%) 5147 CD4 median (cells/mm 3 ) CD4 <50 cells/mm 3 (%) 1311 HBV or HCV +ve (%) 1412 HIV subtype B (%) 6766 Molina J, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1250d

CASTLE: HIV RNA <50 c/mL (CVR, NC = F) Percent HIV RNA <50 c/mL Weeks B/L ATV/r + TDF/FTC (n=440) LPV/r + TDF/FTC (n=443) HIV RNA <50 c/mL: 74% ATV/RTV vs 68% LPV/RTV Difference estimate: 6.1 (95% CI, 0.3%–12.0%, P<0.05) Molina J, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1250d

CASTLE: Response by Baseline HIV RNA and CD4 N= Responder (%) <50 copies/mL % 70% 74% 66% <100,000 c/mL≥100,000 c/mL ITT-Confirmed Virologic Response (NC =F) by Qualifying HIV Viral Load ATV/r + TDF/FTC LPV/r + TDF/FTC ≥200 cells/mm <200 cells/mm 3 N= Responder (%) <50 copies/mL P =NS ITT-Confirmed Virologic Response (NC =F) by Baseline CD4 Cell Count % 71% 78% 71% 69% 70% 58% 69% ATV/rLPV/r P =NS Molina J, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1250d 50 - <100 cells/mm 3 < 50 cells/mm 3

CASTLE: Adverse Events at 96 Weeks ATV/r + TDF/FTC (n=441) LPV/r + TDF/FTC (n=437) Death1% SAE14%11% AE leading to discontinuation 3%5% Jaundice/ hyperbilirubinemia <1% 0 Diarrhea02% Renal<1% Molina J, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1250d *Lipid Changes are Mean Percent Increase From Baseline

CASTLE: Mean Fasting Lipids at Baseline and Week 96 Difference Estimate (95% CI) ATV/r-LPV/r -8.9%* (-11.6%, -6.1%) -1.7% (-5.9%, 2.6%) -5.5% (-10.0%, -0.8%) -9.7%* (-13.0%, -6.3%) -24.5%* (-29.9%, -18.8%) * P< Molina J, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1250d

Meta-Analysis of TDF/FTC vs ABC/3TC in Boosted PI Trials ● 12 clinical trials (N=4896) ● Aggregate results favor TDF/FTC 50%60%70%80%90%100% % HIV RNA <50 copies (ITT TLOVR) at Week 48 SQV/r DRV/r FPV/r LPV/r TDF (n=53) ABC (n=722) TDF (n=2285) ABC (n=722) TDF (n=166) TDF (n=343) TDF (n=493)ATV/r ABC (n=112) Hill A, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1254

Convergence of First-line Regimens ● Treatment-naïve patients at U of Alabama not participating in a clinical trial ● Over time, significant decline in first-line regimen variability ● In 2007, 95% started one of two regimens: TDF/FTC/EFV or TDF/FTC + ATV/r ● Fewer changes of therapy with TDF/FTC/EFV (10%) vs. ZDV/3TV + EFV (43%) Number Started on a Unique Regimen/ Number of Patients Started on ARVs Annual Treatment Share for All Regimens Utilized as Initial Therapy FTC/TDF/EFV 3TC/ZDV/LPV/r 3TC/ddI/EFV 2003 (n=67)2004 (n=75)2005 (n=68)2006 (n=66)2007 (n=65) 3TC/ZDV/EFV 3TC/ZDV/NFV FTC/TDF/ATV/r 3TC/ABC/ZDV 3TC/ZDV/NVP Other – (<5% Treatment Share) McKinnell J, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1260

Issues Regarding ARV Therapy in Treatment-Experienced Patients

TITAN: Study Design LPV-naïve, treatment- experienced VL >1,000 copies/mL Stable HAART for ≥12 weeks (STI allowed) DRV/r 600/100mg bid + OBR (n=298) LPV/r 400/100mg bid + OBR (n=297) Rollover and follow-up phase after 1 and 4 weeks Screening phase (4 weeks) Treatment phase (96 weeks) 595 patients randomised and treated STI = structured treatment interruption; OBR = optimized background regimen Bánhegyi D, et al. 9th ICDTHI; Glasgow, Scotland; November 9-13, Abst. P022.

TITAN: Results at 96 Weeks Patients <50 copies/mL (%) DRV/r LPV/r Previously Used PIs** Primary PI Mutations** Overall P=0.154P<0.0001P=0.078P=0.007P<0.001* *Non-inferiority; **at baseline CD4 Cell Change: DRV/r 93 cells/mm 3 vs. LPV/r 81 cells/mm 3 Virologic Failures: DRV/r 14% vs. LPV/r 26% (p<0.001) Bánhegyi D, et al. 9th ICDTHI; Glasgow, Scotland; November 9-13, Abst. P022.

TITAN: Adverse Events and Median % Change in Lipids at Week 96 *p<0.05 vs LPV/r **p<0.01 vs LPV/r Notable Grade 2-4 AEs Diarrhea: DRV/r 8% vs. LPV/r 15% (p=0.007) Rash: DRV/r 3% vs. LPV/r 1% (p=0.09) No notable differences regarding laboratory abnormalities DRV/r LPV/r Median change from baseline (%) 31%* 12%** 10% 4%** 44% 18% 13% TriglyceridesTotal cholesterol LDL calculated HDL 10% Bánhegyi D, et al. 9th ICDTHI; Glasgow, Scotland; November 9-13, Abst. P022.

BENCHMRK: Resistance Analysis ● Genotyping of BENCHMRK virologic failures (VF) ○ Population sequencing ○ GT at Baseline, VF (HIV RNA >400), and time point(s) post VF ○ 105 VFs (out of 462 on RAL) ○ 94 VFs with BL and VF data ○ 30 VFs with no changes at VF ○ 64 VF included in this analysis ● Patients who fail RAL develop mutational patterns associated with high level resistance First failure: 27% at position 148 Subsequent: 53% at position 148 Miller M, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-898 Number of Mutations Changes from Baseline Genotype Number of Genotypes

BENCHMRK: Pharmacokinetics and Pharmacodynamics Trough concentrations do not predict RAL effectiveness Prolonged pre-integration complex binding may explain the lack of correlation with trough concentration Miller M, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-898 P24 at 48h remove 6, 8, 10 or 12h post infection Infect No Wash6 h8 h10 h12 h No drug RAL RAL “Post-Antibiotic” Effect (in vitro) % patients with HIV RNA <400 c/mL GM Observed C 12hr (nM) GM Observed C 12hr <33 nM RAL Effective Across Range of Trough Levels

ACTG 5211: Analysis Using Enhanced Sensitivity Tropism Testing Trofile ES reclassified 25/114 individuals with R5 virus at screen using original Trofile Original TrofileTrofile ES ScreenEntryAt FailureDM at Screen (n, %) R5DMDM/X47/12, 58% R5 DM/X49/18, 50% R5 9/84, 11% Screening: R5 tropism by the original Trofile assay VCV 5*, 10 or 15 mg QD or Placebo Optimized ART regimenFailing ART regimen Study Screen Study Entry Day 14 Week 24 Week 48 Su Z, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-895 *Stopped early

ACTG 5211: Response Based on Trofile ES Enhanced sensitivity tropism (Trofile ES) testing: ● Detects greater numbers of D/M and X4 virus and improves response rate with CCR5 antagonist regimen ● Excludes only a small number of patients who would respond to CCR5 antagonist ● Role of repeat tropism testing not yet clarified Day 14 Week 24 Trofile ES D/M Screen R5 Screen D/M Entry R5 Screen R5 Entry N15564 Mean HIV RNA Change* Adjusted p value**< Reference N14558 Mean HIV RNA Change* Adjusted p value** Reference Su Z, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-895 * log10 c/mL** From regression model adjusted for baseline HIV-1 RNA and study stratification factors

Randomization 1:1 Patient eligibility criteria: -Treatment naive -R5 HIV-1 infection with HIV RNA ≥2000 c/mL -No resistance to EFV, 3TC or ZDV Patients stratified by: -HIV-1 RNA < and ≥100,000 copies/mL at screening -Geographic location: No. and So. Hemispheres MVC (300 mg BID)* + ZDV/3TC** MERIT: Efavirenz vs. Maraviroc in ARV-Naïve Patients EFV + ZDV/3TC** Week 48 Primary Analysis Week 96 *MVC QD arm discontinued at week 16 for failure to meet protocol-defined criteria to continue **In event of toxicity, ZDV or 3TC switch to alternative NRTI allowed Saag M, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1232a

MERIT ES: Re-analysis of CCR5 Screening Screened as R5 by Standard Trofile Rescreened as D/M by Trofile ES NBL D/M on study EFV + ZDV/3TC n/N (%) MVC + ZDV/3TC n/N (%) Total n/N (%) 23D/M- 4/10 (40.0) 7/13 (53.8) 11/23 (47.8) 29R5YES 6/9 (66.7) 10/20 (50.0) 16/29 (55.2) 615R5NO 46/314 (14.6) 29/301 (9.6) 75/615 (12.2) Saag M, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1232a

MERIT ES: Viral Suppression Using Enhanced Tropism Testing *Lower bound of 1-sided 97.5% confidence interval; noninferiority margin = –10% Saag M, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1232a MVC + ZDV/3TC EFV + ZDV/3TC <400 copies/mL Patients (%) n= –3.0 (–9.5*) 0.6 (–6.4*) MERIT MERIT ES <50 copies/mL –0.2 (–7.4*) n= –4.2 (–10.9 * ) MERIT MERIT ES

MERIT ES: Summary of Discontinuations through 48 Weeks Reason for discontinuation EFV + ZDV/3TCMVC + ZDV/3TC MERIT (N=361) MERIT ES (N=303) MERIT (N=360) MERIT ES (N=311) All, n (%) 91 (25.2)78 (25.7)97 (26.9)76 (24.4) Adverse event*, n (%) 49 (13.6)43 (14.2)15 (4.2)13 (4.2) Lack of efficacy, n (%) 15 (4.2)12 (4.0)43 (11.9)29 (9.3) Other reason, n (%) 9 (2.5)9 (3.0)13 (3.6)11 (3.5) Withdrew consent or lost to follow-up, n (%) 18 (5.0)14 (4.6)25 (6.9)22 (7.1) Only patients with an R5 screening result by enhanced Trofile assay are included in MERIT ES *All cause events Saag M, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1232a

Week 96 Data: Includes all patients who reached Week 48 with HIV-1 RNA <50 c/mL and continued on blinded therapy or open-label MVC BID MOTIVATE 1 & 2: Trial Design 1076 ARV-experienced patients MVC 150mg † BID (n=426) MVC 150mg † QD (n=414) Placebo (n=209) R5 HIV-1 infection (44% screen failures) HIV-1-RNA ≥ 5,000 copies/mL Stable pre-study ARV regimen, or no ARVs for ≥ 4 weeks Resistance to and/or ≥ 6 months’ experience with ≥ 1 ARV from 3 classes (≥ 2 for PIs) MOTIVATE 1 & 2 2 identical ongoing Phase IIb/III studies Randomized (1:2:2), double-blind, placebo controlled All received OBT* Stratified by ENF use and HIV-1 RNA < and ≥ 100,000 copies/mL *OBT = optimized background therapy of 3–6 ARVs (PK boosting doses of RTV not counted as an ARV) †Pts receiving a PI (except TPV) and/or delavirdine in their OBT received 150 mg of MVC, all others received 300 mg of MVC Hardy D, et al. 9th ICDTHI; Glasgow, Scotland; November 9-13, Abst. O425.

MOTIVATE 1 & 2: HIV-1 RNA <50 Copies/mL at Week 96 (ITT, NC=F) Placebo + OBT (N=209) MVC QD + OBT (N=414) MVC BID + OBT (N=426) Hardy D, et al. 9th ICDTHI; Glasgow, Scotland; November 9-13, Abst. O425.

Weighted OBT Sensitivity Score (wOBTSS) MOTIVATE: Using a Weighted Score for the OBT to Predict Response Any drug in continuous use, score = 0 IC 50 FC S*R** PI10 NRTI0.50 NNRTI10 Genotype SR ENF10 Full analysis set (N=1,049) On-study at Week 48 or virologic failure (n=904) Virologic Outcomes (VO) population (n=634) Population included in regression modeling (n=628) Valdez H, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1221 *IC50 fold-change is less than or equal to the lower clinical cut-off **IC50 fold-change is greater than the lower clinical cut-off Non-virologic failures excluded (n=145) Missing / incomplete information (n=6) Exclusions for protocol violations and other reasons (n=270)

MOTIVATE: Results of Using Weighted Score for OBT Conclusions: Using a modified score of the optimized background regimen, and limiting the population to patients with a CD4 count >50, MVC was associated with an ~80% response rate at Wk 48 Proportion of subjects with HIV RNA <50 copies/mL at Week 48 by wOBTSS Subjects ≥50 CD4+ cells/mm 3 at baseline n= <50 copies/mL at Week 48 (%) All subjects Valdez H, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1221 PBO + OBT MVC QD + OBTMVC BID + OBT wOBTSS<11-<2≥2<11-<2≥2 n=

Etravirine + Raltegravir + OBT: Data from the Expanded Access Programs ● Cohort Kaiser Permanente cohort starting ETR + RAL + OBT (n=53) ○ Three class experienced and HIV viremia ○ Resistance (or intolerance) within each class (NRTI, NNRTI, PI) Baseline Demographics Gender, male, n (%)50 (94%) Mean age, years49 Median baseline CD4 count, cells\mm 3 (IQR)171 (74-290) Received boosted protease inhibitor (PI) as part of OBT, n (%)47 (89%) DRV/r44 (83%) de novo use43 (81%) not de novo use1 (2%) LPV/r3 (6%) de novo use1 (2%) not de novo use2 (4%) ATV/r1 (2%) de novo use0 (0%) not de novo use1 (2%) Received enfuvirtide as part of OBT, n (%)6 (11%) de novo use4 (8%) Kerrigan H, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1263

Etravirine + Raltegravir + OBT: Outcomes at Week 24 Virologic and Immunologic Outcomes at Week 24 ( ITT) HIV-1 RNA <75 c/mL, n (%)50 (94%) Mean CD4 cell count change+86 cells\mm 3 Virologic Outcomes at Week 24 based on Baseline and Cumulative Resistance ETR Weighted Mutation Score Number of Patients with HIV-1 RNA <75 c/mL at Week 24, Based on: Baseline Resistance Assessment, n (%) Cumulative Resistance Assessment, n (%) 0-2 Highest Predicted response 35/37 (94.6%)28/30 (93.3%) 2.5 – 3.5 Intermediate Predicted response 9/10 (90.0%)10/10 (100%) >3.5 Reduced Predicted response 6/6 (100%)12/13 (92.3%) The combination of ETR + RAL + OBT was safe and tolerable with minimal adverse events Most common AEs were nausea (5), diarrhea (9) and rash (10) Kerrigan H, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1263

Bevirimat: Phase II Safety and Efficacy Data ● Maturation Inhibitor ○ Not metabolized through CYP3A4 ● Phase II study: Placebo vs. dose ranging BVM (n=88) ○ PK: Target Cmin (≥20 μg/ml) achieved with liquid dose of ≥250mg QD ○ Safety ○ Only grade 1 clinical AEs observed over 2 week period ○ Lab AEs grade >2: 4% AST, 8% glucose elevation ○ BVM activity affected by GAG polymorphism (PM) pattern at codons ○ 62% of 1034 patients are free of Gag PM pattern that predicts poor response to BVM ● Phase 3 planned with tablet formulation and GAG PM screening Lalezari J, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-891 Effect of GAG Polymorphisms on BVM Activity Viral Suppression (log 10 c/mL)

Elvucitabine: 48 Week Results in ARV-Naïve Patients Novel L-cytosine NRTI: ● hour half-life ● In-vitro activity with M184V/I mutation Study Design: ● Randomized to ELV (10mg) or 3TC (300mg) QD ○ Plus TDF and EFV QD (blinded for first 12 weeks) Results: ● Similar virologic suppression in ELV and 3TC arms ● More AE discontinuations with ELV ○ First 12 weeks - 6 more on ELV vs. LAM (multiple reasons) ○ After week 12 – DC rates the same Conclusion: ○ ELV showed similar activity to 3TC to week 48 DeJesus E, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-892

RDEA806: Activity of a Novel NNRTI ● New NNRTI ○ in vitro activity against K103N ○ No inhibition / induction of CYP450 ○ Half-life 9-12 hours ● Proof of Concept Study (n=48) ○ 7 day treatment period using multiple doses of RDEA806 vs. placebo ○ Activity demonstrated and dependent on C trough ○ No safety concerns identified ○ Uric acid reduced ● Phase 2b in ARV treatment- naïve patients planned Moyle G, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-893 Viral Load Reduction and C trough by Cohort

DUET: Impact of Treatment on Hospitalization and Clinical Illness ETR + BR (n=599) Placebo + BR (n=604) Proportion of patients hospitalized (%) 23% 17.5% P= Proportion of patients hospitalized by Week 48 Proportion of patients with any AIDS-defining illness or death Patients with any AIDS-defining illness or death (%) Overall population ENF not de novoENF de novo 0 5.8% 9.8% 7.2% 8.8% 5.4% 10.1% P=0.0408P=0.6114P= Haubrich R, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1239

Management Strategies in Patients on ARV Therapy

FOTO: Five Days On, Two Days Off Study Design VL < 50 c/mL on TDF / FTC /EFV Continue daily ARV treatment (n=30) Change to Five days On; Two Days Off (n=30) Primary Outcome: 24 weeks* *At week 24 – pts. on Continuous arm offered change to FOTO; all followed for >48 weeks Male (%) 83% White (%) 77% 63% Age (years) 4742 CD4 count (cells/mm 3) Cohen C, et al. 9th ICDTHI; Glasgow, Scotland; November 9-13, Abst. O214.

FOTO Results: Primary Outcome *p<0.05 to reject hypothesis that FOTO is inferior to continuous Week 24: VL < 50 c/mL Patient Percent Cohen C, et al. 9th ICDTHI; Glasgow, Scotland; November 9-13, Abst. O214.

FOTO: Additional Outcomes *Missing = Excluded; **p<0.05 for inferiority ** %<50 c/mL to week 24 (OT*) ● Adverse Events: ○ No drug-related SAEs ○ No grade >3 AEs in either arm ○ Labs: No Grade >2 in either arm ● Pt. Preference Questionnaire – Week 4 on FOTO arm ○ Scale: 0 (prefer Continuous) to 10 (prefer FOTO) ○ Result: Median 9.5 (range 2-10) Cohen C, et al. 9th ICDTHI; Glasgow, Scotland; November 9-13, Abst. O214.

AI-073: Switching Suppressed Patients to EFV/FTC/TDF STR=EFV/FTC/TDF QD (n=203) SBR=Stayed Baseline Regimen (n=97) Randomization 2:1 Stratify by PI or NNRTI Continue Switch VL<200 c/mL Stable ARV Regimen On 1st regimen or suppressed on previous PI regimen No H/O VF Phase IV, multicenter (55 US sites), open-label study (N=300) Primary Endpoint: Non-inferiority of STR vs. SBR for HIV-1 RNA <200 c/mL through Week 48 by TLOVR analysis DeJesus E, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1234; Young B, et al. 9th ICDTHI; Glasgow, Scotland; November 9-13, Abst. P061.

AI-073: Results at 48 Weeks Virologic failureSTR 3, SBR 1 AE’s all grades STR: Higher incidence - Sleep disturbance 14% vs 0 -Dizziness 11% vs 1% -GI (nauseas, diarrhea) 6% vs 2% DC due to AE’sSTR 10 (5%), SBR 1 (1%) GFR (CG, MDRD)No significant changes Change TG (mg/dl)STR -20, SBR -3 (P=0.035) Pt preferenceSTR 91%, SBR 9% (P=0.001) % with HIV RNA <50 c/mL (TLOVR) Treatment Difference (STR – SBR) 95% CI:2.6% (5.9%, 11.1%) DeJesus E, et al. 48th ICAAC/46th IDSA; Washington, DC; October Abst. H-1234; Young B, et al. 9th ICDTHI; Glasgow, Scotland; November 9-13, Abst. P061.

The 48th Interscience Conference on Antimicrobial Agents and Chemotherapy and 46th Infectious Disease Society of America Meeting Washington, DC October 24-28, 2008 and 9 th International Congress on Drug Therapy in HIV Infection Glasgow, Scotland November 9-13, 2008