1. Results of the STACCATO trial 1 The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand, 2 Geneva University Hospital, Geneva, Switzerland, 3 University Hospital, Bern, Switzerland, 4 Bamrasnaradura Institute, Bangkok, Thailand, 5 Khon Kaen University, Khon Kaen, Thailand, 6 Mahidol University, Bangkok, Thailand, 7 NCHECR, Sydney, Australia CD4-guided scheduled treatments interruptions (STIs) compared to continuous therapy (CT) : Jintanat Ananworanich 1, Angele Gayet-Ageron 2, Michelle Le Braz 2, Hans-Jakob Furrer 3, Wisit Prasithsirikul 4, Ploenchan Chetchotisakd 5, Sasisopin Kiertiburanakul 6, Praphan Phanuphak 1, David A. Cooper 7, Kiat Ruxrungtham 1, Bernard Hirschel 2, and The Staccato Study Group

2. Staccato Study Design HAART-treated Patients with CD4 > 350 and VL < 50 (n = 548) CD4-guided arm (STI) ( n = 299) Continuous treatment arm (CT) (n = 154) Week on Week off Prematurely Terminated (n = 44) 284 patients analyzed146 patients analyzed Stop at CD4 > 350 Start at CD4 < 350 Continue HAART Last 12 – 24 weeks, all patients treated with continuous HAART in order to compare VL response At a median FU of 21.9 months: CD4, ARV savings, AE compared

3. Baseline Characteristics CD4-guided N = 284 Continuous N = 146 Median age in years (range)35.2 (17-70)35.9 (21-70) Gender (% male)138 (48.6)60 (41.1) Men who have sex with men Heterosexual transmission Others 46 (16.2) 228 (80.3) 9 (3.5) 20 (13.7) 117 (80.1) 8 (6.2) CDC A CDC B CDC C 171 (60.2) 90 (31.7) 23 (8.1) 88 (60.3) 42 (28.8) 16 (10.9) Median CD4 cells/  L (IQR) 470 (398-619)506 (397-600) Median pre-ARV CD4 cells/  L (IQR) 267 (205-339)253 (201-334) Median pre-ARV HIV RNA (log10 copies/mL) (IQR) 4.72 (4.28-5.25)4.76 (4.31-5.17) Median duration of prior ARV treatment in months (IQR) 13.7 (6.7-34.1)15.6 (7.0 – 34.3)

4. Population and HAART Regimens RegimenPatient daysPercent of total Ritonavir-boosted saquinavir 8729780.0 Other protease inhibitor- based regimens 45474.2 Non-nucleoside reverse transcriptase inhibitors 1528414.0 3 nucleoside reverse transcriptase inhibitors 19451.8 80% from Thailand 18.5% from Switzerland 1.5% from Australia

5. AIDS-defining Illnesses and Death n No patient had AIDS-defining illness n There were 2 deaths –One in CT arm from stroke –One in STI arm from colon cancer

6. Proportion of Patients with CD4 > 350 % with CD4 > 350 STICT Median CD4 374 601 IQR 312 – 452472 - 696 P < 0.001

7. Median CD4 (IQR) During the Randomization Period P < 0.002

8. Proportion of Patients with Viral Load < 50 copies/ml after 12-24 Weeks of HAART Re-treatment % VL < 50 copies/ml P = 0.90 Virological Failure in 9 STI and 6 CT patients Resistance mutations not different between arms (~ 2%) Poster 622B

9. Adverse Events % with AE P = 0.04 P = 0.03 P = 0.04 Only seen in STI arms Acute Retroviral Syndrome in 5.7% (Confirmed high VL in 2.5%) Thrombocytopenia in 2.5%

10. mmol/L % with LD P < 0.05 Lipids Self-reported lipodystrophy At End of Randomization

11. Actual Time on ARV % Time on ARV 61.5% ARV Savings

12. Summary n Compared to the CT arm, STI arm had –No AIDS-defining illnesses –More oral/vaginal candidiasis, thrombocytopenia and acute retroviral syndrome –Lower median CD4 count –Similar VL response to HAART retreatment –Low and similar rates of resistance –Less ARV-related diarrhea and neuropathy –Lower lipids and self-reported lipodystrophy –62% ARV savings

13. StaccatoTrivacanSMART N of pts4303265472 PY FU (in STI arm)490?3062 CD4 at Stop CD4 at Start 350 250 350 250 Median age (years)353446 AIDS, death/100PY STI CT 0.2 0.4 17.6 6.7 3.1 1.4 Oral and vaginal candidiasis STI CT 2.28 0.34 6.4 2.3 ???? Time on ARV before study (mo) 15772

14. Conclusion n The incidence rates of SMART would have produced approximately 17 AIDS-defining opportunistic events or deaths in Staccato's STI group, whereas no AIDS- defining event and only one death was observed n Staccato had a higher CD4 restart criterion than Trivacan and SMART (350 vs 250) n The time on ARV before the trial in SMART was much longer than in Staccato (72 vs 15 months) n The results of the different STI studies need to be compared carefully

15. The Staccato Study Group Bernard Hirschel, Kiat Ruxrungtham, Wisit Prasithsirikul, Ploenchan Chetchotisakd, Sasisopin Kiertiburanakul, Warangkana Munsakul, Phitsanu Raksakulkarn, Somboon Tansuphasawadikul, Praphan Phanuphak, David A. Cooper, Jintanat Ananworanich, Sasiwimol Ubolyam, Apicha Mahanontharit, Jongkol Sankote, Sunee Sirivichayakul, Saijai Wicharuk, Siriporn Nonenoy, Natnipa Wannachai, Thidarat Jupimai, Sukontha Saenawat, Sineenart Chautrakarn, Theshinee Chuenyam, Thantip Nuchapong, Suchittra Putthawong, Sirirat Liganonsakul, Wattana Sanchiem, Parichat Seawsirikul, Wiphawee Kiatatchasai, Vantanit Pairoj, Nawaporn Seekaow Wipawan Karakate, Wirat Klinbuayam, Yaowaluk Penglimoon, Siraporn Artharn, Sopha Khongsawad, Pongpan Boonchoo, Malee Suannum, Angele Gayet-Ageron, Michelle Lebraz, Matthias Cavassini, Claudia Satchell, Sabine Yerly, Andrew Hill, Véronique Schiffer, Laurent Kaiser, Hansjakob Furrer, Reto Nuesch, Daniel Genné, Urs Karrer, Matthias Cavassini, Pietro Vernazza, Enos Bernasconi, Lorenzo Magenta, Dominic Leduc

16. Acknowledgement n The Swiss Cohort Study funded this study n We are grateful to Roche for providing unrestricted research funds for this study and for providing Invirase ® during and after the study n We thank Gilead for providing Viread ® and Emtriva ® during the study, and Abbott for providing Norvir ® during the study