Key HIV Research From ICAAC 2007: First-Line Antiretroviral Therapy and Switching Strategies

1. Key HIV Research From ICAAC 2007: First-Line Antiretroviral Therapy and Switching Strategies Faculty: Chicago, Illinois | September 17-20, 2007 Cal Cohen, M.D., M.S. Eric Daar, M.D. This activity is supported by an educational grant from:

2. Faculty for This Activity Dr. Cohen is the research director of the Community Research Initiative of New England and teaches at Harvard Medical School in Boston, Mass. In addition, he works as a HIV clinical management consultant and internist at Harvard Pilgrim Health Care, Boston, Mass., and is affiliated with Harvard Vanguard Medical Associates. Dr. Cohen was co-chair of the Scientific Advisory Committee of amfAR community-based clinical trials network, and served as co-principal investigator of the Harvard/BCH AIDS Clinical Trials Unit, AIDS Clinical Trials Group. He holds appointments at Brigham and Women's Hospital and Beth Israel Hospital, both in Boston, Mass. Cal Cohen, M.D., M.S. Dr. Daar is the chief of HIV medicine at Harbor-UCLA Medical Center in Los Angeles, Calif., and a professor of medicine at the University of California-Los Angeles' David Geffen School of Medicine. He has been an active HIV physician and researcher since the 1980s; during the past three decades, he has led dozens of studies on a vast range of HIV-related issues, with a particular focus on coinfections and other health complications associated with HIV and HIV treatment, including hepatitis C, metabolic complications, cardiovascular disease and psychosocial issues such as depression. Eric Daar, M.D.

3. ICAAC 2007: First-Line Antiretroviral Therapy and Switching Strategies About this slide presentation • This presentation is one of three slide sets created to accompany The Body PRO's podcast summary of key research presented at ICAAC 2007, featuring interviews with Cal Cohen, M.D., M.S., and Eric Daar, M.D. To download the remaining slide sets or learn more about this CME/CE program, please visit us on the Web at: TheBodyPRO.com/ICAAC2007 • Please feel free to use this slide presentation for personal reference or for your own presentations; however, we ask that you not modify any aspects of the slides contained within this presentation, so proper attribution can be retained. If you would like to publish all or part of this presentation, or repost any of these slides online, permission must first be obtained from Body Health Resources Corporation. • Our gratitude goes out to all who granted permission for their slides to be adapted for this presentation. Disclaimer Knowledge about HIV changes rapidly. Note the date of this presentation's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this presentation.

4. First-Line Antiretroviral Therapy

5. ARTEMIS: Phase III Study Design DRV/r 800/100mg qd + TDF 300 mg and FTC 200 mg (N=343) 689 ARV-naïve patients VL>5,000; no CD4 entry LPV/r 400/100mg bid or 800/200mg qd + TDF 300 mg and FTC 200 mg (N=346) Dosing was based on regulatory approval; switch was made according to local regulatory approval and drug availability Edwin DeJesus et al. ICAAC 2007; abstract H-718b. Reprinted with permission.

6. ARTEMIS: Baseline Characteristics DRV/r qd (N=343) LPV/r qd or bid (N=346) 104 (30) 36 (9) 40/23/23 105 (30) 35 (9) 44/21/22 Baseline demographics Female, N (%) Mean (±SD) age (yrs) Caucasian/Black/Hispanic, % Baseline disease characteristics Median HIV-1 RNA (cpm) (range) Median CD4 (cells/mm3 [range]) HBV/HCV co-infected, n (%) 70,800 (835–5,580,000) 228 (4–750) 43 (13) 62,100(667–4,580,000) 218 (2–714) 48 (14) Stratification factors at screening CD4 count <200 cells/mm3 Plasma HIV-1 RNA ≥100,000 cpm 40% 36% 41% 36% Edwin DeJesus et al. ICAAC 2007; abstract H-718b. Reprinted with permission.

7. ARTEMIS: Viral Load <50 copies/mL to Week 48 (ITT-TLOVR) 100 DRV/r qd (N=343) LPV/r qd or bid(N=346) 90 84% 80 78% 70 60 Patients with VL <50 copies/mL (% [±SE]) 50 40 Estimated difference in response vs LPV/r for non-inferiority: PP = 5.6% (95% CI –0.1;11.3) p<0.001 Estimated difference in response vs LPV/r for superiority: ITT = 5.5% (95% CI –0.3;11.2) p=0.062 Estimated difference in response vs LPV/r for non-inferiority: PP = 5.6% (95% CI –0.1;11.3) p<0.001 30 20 10 0 2 4 8 12 16 24 36 48 Time (weeks) Edwin DeJesus et al. ICAAC 2007; abstract H-718b. Reprinted with permission.

8. DRV/r qd LPV/r qd or bid ARTEMIS: Confirmed Response by Baseline Viral Load or CD4 at Week 48 (ITT-TLOVR) 100 100 †p<0.05 vs LPV/r 87 86 85 84 n=194 79† n=191 n=28 80 80 80 77 71 67 67 60 60 Patients with VL <50 copies/mL (%) Patients with VL <50 copies/mL (%) 40 40 20 20 0 0 0 <100,000 ≥100,000 <50 50–200 >200 Baseline viral load (copies/mL) Baseline CD4 cell count (cells/mm3) N = 226 226 117 120 N = 30 30 111 118 202 198 †Chi square analysis Edwin DeJesus et al. ICAAC 2007; abstract H-718b. Reprinted with permission.

9. ARTEMIS: Virologic Failure (VF)and Emergence of Mutations DRV/r qd LPV/r qd or bid (N=343) (N=346) VF (> 50 cpm) 34 (10%) 49 (14%) VF (> 400 cpm) 11 (3%) 18 (5%) 10 18 Paired baseline and VF genotype available IAS-USA PI RAMS 0 1* 1† IAS-USA NRTI mutations 2† †184V *A71T, V77I VF by TLOVR *IAS-USA mutations, Fall 2006; Johnson et al. Topics in HIV Medicine. 2006; 14:125-130 Edwin DeJesus et al. ICAAC 2007; abstract H-718b. Reprinted with permission.

10. ARTEMIS: Grade 2–4 Adverse Events (AEs) p<0.01 p<0.05 †At least possibly related to study drug, excluding laboratory-related events • No renal SAEs and no treatment discontinuations due to renal AEs Edwin DeJesus et al. ICAAC 2007; abstract H-718b. Reprinted with permission.

11. ARTEMIS: Conclusions • The use of once-daily DRV/r 800/100mg + TDF/FTC in treatment-naïve patients: • resulted in excellent virologic and immunologic responses • provided suitable exposure in all patients • was well tolerated, with a favorable safety profile • In comparison to the LPV/r arm* in treatment-naïve patients: • For efficacy, DRV/r 800/100mg qd was non-inferior in the overall population, and superior in patients with high VL • DRV/r had lower incidence of common GI toxicities and triglyceride elevations *LPV/r arm included: LPV/r 400/100mg bid or 800/200mg qd, capsule and tablet formulations Edwin DeJesus et al. ICAAC 2007; abstract H-718b. Reprinted with permission.

12. ICAAC 2007: First-Line Antiretroviral Therapy and Switching Strategies • Visit The Body PRO for Comprehensive Coverage of ICAAC 2007.This presentation is one of three slide sets created to accompany The Body PRO's podcast summary of key research presented at ICAAC 2007, featuring interviews with Cal Cohen, M.D., M.S., and Eric Daar, M.D. To download the remaining slide sets or learn more about this, please visit us on the Web at: TheBodyPRO.com/ICAAC2007 • In addition, be sure to browse through The Body PRO’s extensive coverage of ICAAC 2007, which includes: • Downloadable MP3s and full transcripts • Expert discussion of key research • Slides and in-depth data analyses • Visit TheBodyPRO.com/ICAAC2007today for a full listing of our conference materials!