1. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 Similar prevalence of baseline HIV-1 minority variants among responders and virologic failures, as well as increased detection of HIV-1 minority variants at treatment failure, in rilpivirine patients from the ECHO and THRIVE Phase III studies L. Rimsky, 1 V. Van Eygen, 1 J. Vingerhoets, 1 K. Thys, 1 J. Aerssens, 1 M. Stevens 1 and G. Picchio 2 1 Janssen Infectious Diseases BVBA, Beerse, Belgium; 2 Janssen Research & Development, LLC, Titusville, NJ, USA

2. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 * HIV-1 quasispecies undetectable by Sanger population sequencing (SPS) and seen only by ultra-deep sequencing (UDS) ¥ 49 RPV responders and 47 RPV VFs from the analysis of the Week 48 pooled ECHO and THRIVE trials with comparable baseline characteristics ‡ 48 RPV VFs including 12 without NNRTI RAMs and NRTI RAMs UDS (Illumina ® platform) with a median coverage of 215,377 reads per position (1% represents ±2000 reads) Assess if baseline minority variants * with resistance-associated mutations (RAMs) in reverse transcriptase (RT) played a role in rilpivirine (RPV) virologic failure (VF) ¥ Describe the minority variants with RT RAMs in RPV patients with virologic failure (VF) at time of failure ‡ Objective (Part 1)

3. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 NNRTI RAMs present at baseline NNRTI RAMs not associated with VF in green; RPV RAMs in red 1 ≥1 V90I V106I V108I E138A V179D V179I V189I F227C Frequency of baseline NNRTI RAMs detected by SPS among responders and VFs to RPV was comparable 1 Rimsky L, et al. JAIDS 2012;59:39–46 * 49 responders and 47 VFs with comparable baseline characteristics SPS = Sanger population sequencing [N = 47] [N = 49]

4. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 NNRTI RAMs present at baseline NNRTI RAMs not associated with VF to RPV in green; RPV RAMs in red 1 ≥1 V90I V106I V108I E138A V179D V179I V189I F227C 2 VFs had minority variants with 1 NRTI RAM at baseline (M184V and L210W) * 49 responders and 47 VFs with comparable baseline characteristics UDS = ultra-deep sequencing; SPS = Sanger population sequencing MVs = minority variants 1 Rimsky L, et al. JAIDS 2012;59:39–46 Frequency of baseline NNRTI RAMs detected by UDS was similar among responders and VFs to RPV [N = 47] [N = 49]

5. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 Additional NNRTI RAMs detected by UDS in RPV VFs at failure UDS = ultra-deep sequencing; SPS = Sanger population sequencing; MVs = minority variants RPV RAMs in red 1 1 Rimsky L, et al. JAIDS 2012;59:39–46 The most commonly found NNRTI RAMs observed in minority variants were the same as those seen by SPS

6. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 The most commonly found NRTI RAMs observed in minority variants were the same as those seen by SPS Additional NRTI RAMs detected by UDS in RPV VFs at failure UDS = ultra-deep sequencing; SPS = Sanger population sequencing; MVs = minority variants VFs [N = 48]

7. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 UDS analysis of 97 RPV patients (49 responders and 48 VFs) from ECHO and THRIVE showed: –Minority variants at baseline did not play a role in RPV VF –Minority variants with NNRTI RAMs were detected at failure in an additional 7 of the 48 RPV VFs. Few NRTI RAMs were detected. These RT RAMs were the same as those seen by SPS –UDS confirmed the RPV resistance findings observed in ECHO and THRIVE Conclusions (Part 1)

8. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 *34/48 RPV VFs with ≥1 of K101E, E138K or M184I/V detected by UDS at failure ¥ Linkage analysis performed on a subset of 6/34 RPV VFs with mixtures of mutations at 2 positions (101 and 138) Objective (Part 2) Determination of the relative frequencies of K101E, E138K and/or M184I/V in a subset of RPV VFs * Analysis of the linkage between K101E and E138K ¥

9. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 Only the 34/48 VFs with at least one of E138K, K101E, M184I and M184V are displayed VFs at failure Frequencies of M184I/V Frequency of quasispecies (%)

10. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 Only the 34/48 VFs with at least one of E138K, K101E, M184I and M184V are displayed VFs at failure Frequencies of M184I/V and E138K Frequency of quasispecies (%)

11. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 Only the 34/48 VFs with at least one of E138K, K101E, M184I and M184V are displayed VFs at failure M184I/V can occur without K101E or E138K K101E or E138K are on the same genome with M184I/V Frequencies of M184I/V, K101E and E138K Frequency of quasispecies (%)

12. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 Frequency of quasispecies (%) VFs at failure Frequencies of M184I/V, K101E and E138K M184I/V can occur without K101E or E138K K101E or E138K are on the same genome with M184I/V

13. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 Linkage analysis: E138K and K101E were usually found in different genomes 146,395 paired-end reads from 6 RPV VFs with K101E/K + E138E/K E K K K E E K E E138K101 Variants with:

14. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 When present in RPV VFs, M184I/V was usually observed at high frequency regardless of the presence of E138K or K101E In RPV VFs, E138K and K101E were usually found in different genomes in association with M184I or V, suggesting different pathways of RPV resistance Conclusions (Part 2)

15. Rimsky L, et al. XIX IAC 2012. Abstract TUAB0302 Editorial support was provided by I Woolveridge of Gardiner-Caldwell Communications, Macclesfield, UK; this support was funded by Janssen Acknowledgements ECHO Argentina: L Abusamra, P Cahn, HE Laplume, I Cassetti, M Ceriotto, M Daniel Martins, A Krolewiecki; Australia: M Bloch, J Gold, J Hoy, P Martinez; Austria: A Rieger, N Vetter, R Zangerle; Brazil: CA Da Cunha, B Grinsztejn, JV Madruga, JH Pilotto, D Sampaio; Canada: P Junod, D Kilby, A Rachlis, S Walmsley; Denmark: J Gerstoft, L Mathiesen, C Pedersen; France: L Cotte, P-M Girard, JM Molina, F Raffi, D Vittecoq, Y Yazdanpanah, P Yeni; Great Britain: M Fisher, M Nelson, C Orkin, S Taylor; Italy: A Lazzarin, P Narciso, A Orani, S Rusconi; Mexico: G Amaya, G Reyes-Teran; Netherlands: B Rijnders; Puerto Rico: J Santana; Portugal: F Antunes, T Branco, R Sarmento E Castro, T Eugenio, K Mansinho; Romania: D Duiculescu, L Negrutiu, L Prisacariu; Russia: V Kulagin, E Voronin, A Yakovlev; South Africa: E Baraldi, N David, O Ebrahim, E Krantz, GH Latiff, D Spencer, R Wood; Spain: JR Arribas, J Portilla Sogorb, E Ribera, I Santos Gil; Sweden: K Westling; Thailand: P Chetchotisakd, T Sirisanthana, S Sungkanuparph, A Vibhagool; Taiwan: C-C Hung, H-C Lee, H-H Lin, WW Wong; USA: H Albrecht, N Bellos, D Berger, C Brinson, B Casanas, R Elion, J Feinberg, T File, J Flamm, C Hicks, S Hodder, C-B Hsiao, P Kadlecik, H Khanlou, C Kinder, R Liporace, C Mayer, D Mildvan, A Mills, RA Myers, I Nadeem, O Osiyemi, M Para, G Pierone, B Rashbaum, J Rodriguez, M Saag, J Sampson, R Samuel, M Sension, P Shalit, P Tebas, W Towner, A Wilkin, D Wohl THRIVE Australia: D Baker, R Finlayson, N Roth; Belgium: R Colebunders, N Clumeck, J-C Goffard, F Van Wanzeele, E Van Wijngaerden; Brazil: CR Gonsalez, MP Lima, F Rangel, A Timerman; Canada: M Boissonnault, J Brunetta, J De Wet, J Gill, K Kasper, J Macleod; Chile: J Ballesteros; R Northland, Carlos Perez; China: L Hongzhou, L Taisheng, W Cai, H Wu, L Xingwang; Costa Rica: G Herrera; France: F Boue, C Katlama, J Reynes; Germany: K Arastéh, S Esser, G Fätkenheuer, T Lutz, R Schmidt, D Schuster, H-J Stellbrink; Great Britain: M Johnson, E Wilkins, IG Williams, A Winston; India: N Kumarasamy, P Patil; Italy: A Antinori, G Carosi, F Mazzotta; Mexico: J Andrade-Villanueva, JG Sierra Madero; Panama: A Canton Martinez, A Rodriguez-French, N Sosa; Portugal: R Marques; Puerto Rico: C Zorrilla; Russia: N Dushkina, A Pronin, O Tsibakova, E Vinogradova; South Africa: M Botes, F Conradie, J Fourie, L Mohapi, D Petit, D Steyn; Spain: B Clotet, F Gutierrez, D Podzamczer, V Soriano; Thailand: K Ruxrungtham, W Techasathit; USA: L Amarilis Lugo, R Bolan, L Bush, R Corales, L Crane, J De Vente, M Fischl, J Gathe, R Greenberg, K Henry, D Jayaweera, P Kumar, J Lalezari, J Leider, R Lubelchek, C Martorell, K Mounzer, H Olivet, R Ortiz, F Rhame, A Roberts, P Ruane, A Scribner, S Segal-Maurer, W Short, L Sloan, T Wilkin, M Wohlfeiler, B Yangco The authors would also like to thank Janssen rilpivirine team members, in particular, D Anderson, and P Williams for their important contributions to the presentation, C Van Hove for sequencing analysis support. The patients and their families for their participation and support during the studies ECHO and THRIVE Janssen study teams and the principal investigators: LR, VVE, JV, KT, JA, MS and GP are full-time employees of Janssen