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DW Cameron 1 , BA da Silva 2 , JR Arribas 3 , R Myers 4 , NC Bellos 5 ,

Oral Presentation #THLB0201. A two-year randomised controlled clinical trial in antiretroviral-naïve subjects using lopinavir/ritonavir monotherapy after initial induction treatment compared to an efavirenz 3-drug regimen. 96 week results, Study M03-613.

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DW Cameron 1 , BA da Silva 2 , JR Arribas 3 , R Myers 4 , NC Bellos 5 ,

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  1. Oral Presentation #THLB0201 A two-year randomised controlled clinical trial in antiretroviral-naïve subjects using lopinavir/ritonavir monotherapy after initial induction treatment compared to an efavirenz 3-drug regimen.96 week results, Study M03-613 DW Cameron1, BA da Silva2, JR Arribas3, R Myers4, NC Bellos5, N Gilmore6, KR Niemi2, KJ Wikstrom2, MS King2, GJ Hanna2, SC Brun2 1University of Ottawa at The Ottawa Hospital, Ottawa, Ontario, Canada 2Abbott Laboratories, Abbott Park, IL, USA 3Hospital La Paz, Madrid, Spain 4Body Positive, Inc., Phoenix, AZ, USA 5Southwest Infectious Disease Associates, Dallas, TX, USA 6Montréal Chest Institute, Montréal, Québec, Canada

  2. LPV/r 400/100 mg BID LPV/r SGC 400/100 mg BID + ZDV/3TC (n=104) Study design and methods LPV/r 400/100 mg BID + ZDV/3TC 96 weeks Screening EFV 600 mg QD + ZDV/3TC (n=51) Rx naïve HIV-1 RNA >1000 Any CD4 count No evidence of resistance to study drugs 2:1 randomisation, open trial VL monitored monthly for 18 months, then every 2 months through month 24 In the LPV/r group, subjects with VL < 50 / mL for 3 consecutive months from month 3 to 11 discontinued ZDV/3TC at the next visit (earliest month 6), and remained on LPV/r monotherapy. Subjects not meeting these criteria remained on LPV/r + ZDV/3TC Primary outcome: HIV-1 viral load < 50 c/mL at week 96 (24 months) Primary analysis: intention-to-treat, prior failure (> 50 c/mL x 2) = failure

  3. Demographics LPV/r(n=104) EFV(n=51) 39 (77%) 35 (18 - 56) 4.8 (3.5 - 6.2) 16 (31%) 250 (3 - 756) 32 (63%)17 (33%)8 (16%)2 (4%) Gender male Age* (years) mean (range) HIV-1 VL** (log10 / mL) mean (range) >100,000/mL CD4 (cells/L) mean (range) Race/ethnicity*** Caucasian Black Hispanic Other 84 (81%) 40 (18 – 73) 5.0 (3.4 - 6.5) 44 (42%) 227 (6 - 773) 68 (65%)29 (28%)6 (6%)7 (7%) * p=0.003 ** p=0.04 *** some state more than one category

  4. Disposition 155 subjects randomised and dosed 104 subjects LPV/r + ZDV/3TC 51 subjects EFV + ZDV/3TC 2 switched to EFV, subsequently d/c 3 switched to LPV/r, subsequently d/c 8 d/c study prior to deintensification 4 switched to LPV/r, remain on LPV/r 15 d/c study after deintensification 10 discontinued study from EFV 8 completed study on LPV/r + NRTIs (2 never deintensified, 6 restarted NRTIs) 34 completed study on EFV + NRTIs 71 completed study on LPV/r alone Median(range) weeks on monotherapy: 68 (56-72) weeks

  5. Discontinuations LPV/r EFV Subjects enrolled Premature discontinuations Reasons for discontinuation1 104 25 (24%) 51 13 (25%) Death2 Adverse Event3 Lost to follow-up Noncompliance Withdrew Consent Virologic failure Other reasons4 2 (2%) 3 (3%) 5 (5%) 3 (3%) 6 (6%) 2 (2%) 10 (10%) 1 (2%) 1 (2%) 4 (8%) 3 (6%) 4 (8%) 0 5 (10%) • Investigator may have indicated more than one reason for discontinuation • Both LPV/r deaths were considered unrelated to LPV/r (Burkitts Lymphoma and ethylene glycol ingestion) • Includes subject who died due to Burkitts Lymphoma • Primarily site closure (n=6) or subject moving out of area (n=5)

  6. Primary outcome analysis: HIV-1 viral load < 50 c/mL (ITT, prior failure = failure)

  7. Secondary outcome analysis: HIV-1 viral load < 50 c/mL (ITT, non-completer = failure)

  8. Secondary outcome analysis: HIV-1 viral load < 500 c/mL (ITT, non-completer = failure)

  9. No. at risk LPV/r Arm EFV Arm 92 67 48 43 36 31 Time from LPV/r monotherapy to 1st of 2 VL > 50 c/mLLPV/r maintenance versus corresponding EFV subjects

  10. No. at risk LPV/r Arm EFV Arm 92 83 63 43 36 31 Time from LPV/r monotherapy to 1st of 2 VL > 500 c/mLLPV/r maintenance versus corresponding EFV subjects

  11. LPV/r LPV/r EFV + NRTIs 100% 100% Discon- Discon- tinued tinued 80% 80% On study, On study, HIV RNA HIV RNA 60% 60% >500 c/mL >500 c/mL On study, On study, 40% 40% HIV RNA 50- HIV RNA 50- 500 c/mL 500 c/mL 20% 20% On study, On study, HIV RNA <50 HIV RNA <50 c/mL c/mL 0% 0% 0 0 16 16 32 32 48 48 64 64 80 80 96 96 0 0 16 16 32 32 48 48 64 64 80 80 96 96 Week Week Week Week Point prevalence of disposition and HIV-1 viral loads

  12. Outcome of HIV-1 viral load breakthrough on LPV/r monotherapy * Re-suppression means at least one subsequent VL measure < 50 c/mL

  13. +289 +240 p=0.12* * Week 96 comparison Week Sample Size LPV/r Arm EFV Arm 104 91 76 51 38 31 CD4 count response(observed data, mean change from baseline)

  14. Detection of genotypic resistance mutations * 2 subjects on monotherapy, and 1 subject on combination therapy

  15. Summary and conclusions • With successful LPV/r + ZDV / 3TC treatment, subsequent LPV/r monotherapy continuously maintained VL suppression in a large proportion of patients • Patients receiving LPV/r monotherapy experienced more VL breakthrough of 50 - 500 c/mL versus EFV + ZDV / 3TC • LPV/r monotherapy VL breakthrough was usually 50 - 500 c/mL • VL breakthrough generally re-suppressed to < 50 c/mL • Detection of drug resistance mutations did not differ in proportion for LPV/r versus EFV • LPV/r monotherapy may provide an alternative treatment option for selected patients

  16. Canada Dr. Anita Rachlis, Toronto Dr. Stephen Shafron, Edmonton Dr. Sharon Walmsley, Toronto France Dr. Laurent Cotte, Lyon Dr. Veronique Joly, Paris Spain Dr. Bonaventure Clotet, Barcelona Dr. Pere Domingo, Barcelona Dr. Fernando Dronda, Madrid Dr. Frederico Pulido, Madrid Dr. Rafael Rubio, Madrid United Kingdom Dr. Philippa Easterbrook, London Prof. Brian Gazzard, London Dr. Clifford Leen, Edinburgh Dr. Ed Wilkins, Manchester Acknowledgements In addition to the authors, we would like to thank the rest of the M03-613 investigators, all study coordinators, and all study participants • United States • Dr. Rafael Campo, Miami, FL • Dr. Paul Cimoch, Fountain Valley, CA • Dr. Calvin Cohen, Boston, MA • Dr. Charles Farthing, Los Angeles, CA • Dr. Joseph Gathe Jr., Houston, TX • Dr. Charles Hicks, Durham, NC • Dr. Harold Katner, Macon, GA • Dr. Harold Kessler, Chicago, IL • Dr. George McKinley, New York, NY • Dr. David Parenti, Washington DC • Dr. Gerald Pierone, Vero Beach, FL • Dr. Robert Redfield, Baltimore, MD • Dr. Patricia Salvato, Houston, TX • Abbott Study 613 study teamMarion DeHaan, Karmin Robinson, Mary Woulfe, Florence McMillan

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