1. Financial disclosures for Dr Hicks Grant support, honoraria and/or advisory board from Abbott, Bristol-Myers Squibb, Boehringer-Ingelheim, Glaxo SmithKline, Merck, Pfizer, Tibotec, Monogram Biosciences, Gilead, Koronis

2. Pooled 24-week results of DUET-1 and -2: efficacy of TMC125 in treatment-experienced HIV-1-infected patients (Abstract 1316) C Hicks, P Cahn, J Leider, G Pialoux, M Peeters, J Vingerhoets and B Woodfall on behalf of the DUET-1 and DUET-2 study groups

3. 24-week primary analysis DUET-1 and -2 differed only in geographical location; pooled analysis was pre-specified Major inclusion criteria: – Plasma viral load >5,000 HIV-1 RNA copies/mL and stable therapy for ≥8 weeks – ≥1 NNRTI mutation,* at screening or in documented historical genotype – ≥3 primary PI mutations at screening Patients recruited from Thailand, Australia, Europe and the Americas Screening 6 weeks 600 patients target per trial 48-week treatment period with optional 48-week extension *BR = darunavir/ritonavir with optimized NRTIs and optional enfuvirtide TMC125 + BR* Placebo + BR* Follow up 4 weeks DUET study design and major inclusion criteria *From extended list of NNRTI mutations (Tambuyzer et al. Abstract 67 EHDRW 2007); BR = background regimen Abstract 1316

4. Baseline characteristics and background ARVs *From extended list of NNRTI mutations used in inclusion criteria; § assessed by phenotypic sensitivity score (PSS); BR = background regimen; Parameter, % or median (range) TMC125 + BR (n=599) Placebo + BR (n=604) Patient demographics Male, % 9089 Caucasian, %70 Disease characteristics Viral load (log 10 copies/mL), median (range)4.8 (2.7–6.8)4.8 (2.2–6.5) CD4 cells (cells/mL), median (range)99 (1.0–789)109 (0.0–912) CDC category C, %5859 Prior ARV use  10 ARVs, % 8083 Darunavir/r, %45 Detectable mutations  2 NNRTI mutations,* % 66  2 IAS USA NNRTI mutations, % 4342  4 primary PI mutations, % 6263 Background regimen Used enfuvirtide (total), %4647 Used enfuvirtide de novo, %2627 Active background agents § = 0, %1716 Active background agents § = 1, %3639 Abstract 1316

5. Patients with viral load <50 copies/mL at Week 24 (primary endpoint; ITT TLOVR) BR = background regimen; CI = confidence interval; ITT = intent-to-treat population; TLOVR = time to loss of virologic response analysis 59% 41% p<0.0001 100 90 80 70 60 50 40 30 20 10 0 Responders (%) ± 95% CIs 04812162024 Time (weeks) Abstract 1316 TMC125 + BR: Placebo + BR: 558 577 553 568 541 562 545 559 Patients remaining on study (n) for: TMC125 + BR (n=599) Placebo + BR (n=604)

6. Mean viral load reduction from baseline (ITT NC=F) BR = background regimen; SE = standard error; ITT = intent-to-treat population; NC=F = noncompleter equals failure analysis; changes below detection limit (<50 copies/mL) were imputed as 49 copies/mL –1.7 –2.4 Mean change in viral load from baseline (log 10 copies/mL) ± SE 0.0 –0.5 –1.0 –1.5 –2.0 –2.5 –3.0 –3.5 Time (weeks) 04812162024 p<0.0001 TMC125 + BR (n=599) Placebo + BR (n=604) Abstract 1316

7. Mean change in CD4 cell count from baseline (ITT NC=F) +86 +67 Mean change in CD4 cell count from baseline (cells/mm 3 ) ± SE Time (weeks) p<0.0001 BR = background regimen; SE = standard error; ITT = intent-to-treat population; NC=F = noncompleter equals failure analysis 100 75 50 25 0 04812162024 TMC125 + BR (n=599) Placebo + BR (n=604) Abstract 1316

8. CD4 cell count increase to 50 cells/mm 3 or above BR = background regimen Patients with CD4 cell count increased to above 50 cells/mm 3 at Week 24 55% 74% At baseline, 36% and 35% of patients in the TMC125 and placebo groups respectively had a CD4 cell count below 50 cells/mm 3 (n=422 in total) At Week 24 in the TMC125 group 74% of these patients had moved above the 50 cells/mm 3 threshold (n=157), compared with 55% in the placebo group (n=115) Abstract 1316 Baseline CD4 cell count <50 cells/mm 3 Placebo + BR (n=209)TMC125 + BR (n=213)

9. Response (<50 copies/mL) according to enfuvirtide use The primary analysis divided patients according to ENF use 56% Patients with viral load <50 copies/mL at Week 24 (%) 62% 67% 34% Using de-novo enfuvirtide p=0.427 Re-using or not using enfuvirtide p<0.0001 Placebo + BR TMC125 + BR 251/446 149/444 102/153 99/160

10. Patients with viral load <50 copies/mL at Week 24 (%) Response (<50 copies/mL) according to baseline darunavir fold change Analysis excludes patients who discontinued except for virologic failure; BR = background regimen; DRV = darunavir; FC = baseline fold change DRV FC 10–40 DRV FC>40 71% DRV FC<10 Placebo + BR TMC125 + BR 56% 57% 30% 44% 2% 100 75 50 25 0 Abstract 1316 246/345 200/35873/129 39/132 31/71 1/67

11. Response (<50 copies/mL) according to number of active background ARVs Patients with viral load <50 copies/mL at Week 24 (%) Number of fully active background ARVs (PSS) 45% 60% 8%a ≥ 30% 67% 74% 7/91 40/88 63/211 120/199 171/257 191/258 Placebo + BR TMC125 + BR Abstract 1316 Analysis excludes patients who discontinued except for virologic failure; PSS = phenotypic sensitivity score; darunavir and enfuvirtide are counted as fully active if FC<10 or used de novo, respectively

12. BR = background regimen; ITT = intent-to-treat population; TLOVR = time to loss of virologic response analysis Response (<50 copies/mL) according to baseline viral load and CD4 cell count 39% Patients with viral load <50 copies/mL at Week 24 (%) 73% 67% 23% 47% 55% 83/ 213 49/ 209 139/ 208 97/ 208 130/ 177 102/ 186 Abstract 1316 Placebo + BR TMC125 + BR 76% <30,000 44% 61% 62% 39% 26% 30,000– 99,999 ≥100,000 Baseline viral load 126/ 165 108/ 174 126/ 206 84/ 213 101/ 228 56/ 217 <5050–199 ≥200 Baseline CD4 cell count

13. Mutations associated with a decreased response to TMC125 Using the data from these trials, 13 baseline mutations were found to be associated with a decreased response to TMC125 (TMC125 RAMs) * : V90I A98G L100I K101E/P V106IV179D/F Y181C/I/VG190A/S These TMC125 RAMs occurred mainly in the presence of other NNRTI mutations K103N is not associated with resistance to TMC125 *A decreased response was defined as ≤75% of the response for patients with zero NNRTI mutations at baseline from the extended NNRTI mutation list; RAM = resistance-associated mutation

14. Response (<50 copies/mL) according to number of TMC125 RAMS The greatest added benefit in the TMC125 versus placebo group was seen in patients with <3 TMC125 RAMs 86% of patients had <3 TMC125 RAMs Patients with viral load <50 copies/mL at Week 24 (%) Number of TMC125 RAMs present at baseline 75% 58% 60% 41% Analysis excludes patients who used de-novo enfuvirtide or discontinued except for virologic failure BR = background regimen; RAM = resistance-associated mutation; ≥ 73/121 59/157 38% 25% 44% Placebo + BR (n=414)TMC125 + BR (n=406) 02040 6080 25% 17% 121/161 64/147 37/64 17/68 13/32 6/24 7/28 3/18

15. Conclusions In treatment-experienced patients, including those with NNRTI resistant virus, TMC125 was superior to placebo – 59% of patients achieved confirmed undetectable viral load (<50 copies/mL) with TMC125 + BR at Week 24 Even in the absence of any other fully active background agents (PSS = 0), with TMC125, 45% of patients achieved undetectable (<50 copies/mL) viral load – response rates increased as more active agents were used in the BR Better responses were achieved in patients with higher CD4 cell counts and lower viral loads for both treatment arms – higher responses were apparent with TMC125 compared with placebo, for all categories of baseline viral load or CD4 cell count 13 TMC125 RAMs were identified – an increasing number of TMC125 RAMs was associated a decreasing response in both treatment arms – in the TMC125 group, the greatest added benefit was seen with <3 TMC125 RAMs – 86% of patients had <3 TMC125 RAMs TMC125 demonstrated significant activity and provides a new treatment option for patients with resistance to other NNRTIs Abstract 1316 BR = background regimen; RAM = resistance-associated mutation;

16. Acknowledgements Argentina: H Ariza, J Benetucci, L Calanni, L Cassetti, J Corral, D David, A Krolewiecki, M Losso, P Patterson, R Teijeiro; Brazil: C A da Cunha, E Kallas, E Netto, J H Pilotto, M Schechter, J Suleiman, A Timerman; Chile: J Ballesteros, R Northland; Costa Rica: A Alvilés Montoya, G Herrera Martinez, A Solano Chinchilla; France: M Dupon, C Katlama, J M Livrozet, P Morlat, C Piketty, I Poizot-Martin; Mexico: J Andrade- Villanueva, G Reyes-Terán, J Sierra-Madero; Panama: A Canton, A Rodriguez, N Sosa; Puerto Rico: J O Morales Ramirez, J L Santana Bagur, R Soto-Malave; Thailand: T Anekthananon, P Mootsikapun, K Ruxrungtham; USA: M Albrecht, N Bellos, R Bolan, P Brachman, C Brinson, F Cruickshank, R Elion, W J Fessel, T Hawkins, S Hodder, T Jefferson, H Katner, C Kinder, M Kozal, D McDonough, K Mounzer, D Norris, W O’Brien, G Pierone, K Raben, B Rashbaum, M Rawlings, B Rodwick, P Ruane, J Sampson, S Schrader, A Scribner, M Sension, D Sweet, B Wade, D Wheeler, A Wilkin, T Wills, M Wohlfeiler, K Workowski. Australia: J Chuah, D Cooper, B Eu, J Hoy, C Workman; Belgium: N Clumeck, R Colebunders, M Moutschen; Canada: J Gill, K Gough, P Junod, D Kilby, J Montaner, A Rachlis, C M Tsoukas, S L Walmsley; France: C Arvieux, L Cotte, J F Delfraissy, P M Girard, B Marchou, J M Molina, D Vittecoq, Y Yazdanpanah, P Yeni; Germany: S Esser, G Fätkenheuer, H Gellermann, K Göbels, F D Goebel, H Jäger, A Moll, J K Rockstroh, D Schuster, S Staszewski, A Stoehr; Italy: A Antinori, G Carosi, G Di Perri, R Esposito, F Mazzotta, G Pagano, E Raise, S Rusconi, L Sighinolfi, F Suter; Netherlands: P H J Frissen, J M Prins, B J A Rijnders; Poland: A Horban; Portugal: F Antunes, M Miranda, J Vera; Spain: P Domingo, G Garcia, J M Gatell, J González-Lahoz, J López-Aldeguer, D Podzamczer; UK: P Easterbrook, M Fisher, C Orkin, E Wilkins; USA: B Barnett, J Baxter, G Beatty, D Berger, C Borkert, C Cohen, M Conant, J Ernst, C Farthing, T File, M Frank, J E Gallant, A E Greenberg, C Hicks, D T Jayaweera, S Kerkar, N Markowitz, C Martorell, C McDonald, D McMahon, M Mogyoros, R A Myers Jr, G Richmond, K Sathasivam, S Schneider, H Schrager, P Shalit, F P Siegal, L Sloan, K Smith, S Smith, P Tebas, L S Tkatch. We express our gratitude to the patients that participated in the study, as well as the study centre staff, DSMB, clinical event adjudication panel, Tibotec personnel and following principal investigators: DUET-1 DUET-2 Abstract 1316