1 / 59

ICAAC 2009: HIV Updates

ICAAC 2009: HIV Updates. Antonio Urbina, MD Medical Director HIV Education St. Vincent’s Comprehensive HIV Center A Local Performance Site of the New York/New Jersey AETC October 2009. Disclosures. Speaker’s Bureau: Monogram, BMS, Gilead, Tibotec, Boehringer-Ingelheim

malo
Download Presentation

ICAAC 2009: HIV Updates

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. ICAAC 2009: HIV Updates Antonio Urbina, MD Medical Director HIV Education St. Vincent’s Comprehensive HIV Center A Local Performance Site of the New York/New Jersey AETC October 2009

  2. Disclosures • Speaker’s Bureau: Monogram, BMS, Gilead, Tibotec, Boehringer-Ingelheim • Research Grant: BMS

  3. HIV in the US • By 2015, 50% of HIV+ individuals will be over 50 (currently it’s 15-20-%) 1 • From 2000 to 2004, persons aged 40-49 years had the highest prevalence of HIV/AIDS and the steepest rise in prevalence • As part of stimulus package, NIH providing funding opportunities to address gaps in knowledge • Immune Function and Host Defenses • Response to Treatment • PK and Pharmacogenomics • Metabolic Complications • Neurologic and Neuropsychiatric Complications • HIV Related Malignancies • Frailty and Functional Status • Complexity of Care 1. CDC MMWR 57:1073-1076

  4. HIV and Pregnancy • Birth Defect Rate with Tenofovir Similar to US Population • Antiretroviral Pregnancy Registry began collecting tenofovir data in 2001 and analyzed 10,471 cases involving any ARV and 1056 involving tenofovir • Congenital anomaly rates with any tenofovir containing regimen (1,2 or 3rd trimester) were similar to general population • Registry has no reports involving entry inhibitors or integrase inhibitors Squires, et al. 49th ICAAC. Abstract H-917

  5. Novel ARV Strategies

  6. Nuc-Sparing Combinations • Raltegravir/Atazanavir • Desirable combination as ATZ inhibits UGT-1 • 30 pt, prospective 48 week single arm switch study • Pts had to be on stable ARVs for at least 2 months with viral load <50 at screening • No history of PI resistance or ARV failure while receiving a PI • And intolerance to current regimen PJ Ruane, et al. 49th ICAAC

  7. Nuc-Sparing Combinations PJ Ruane, et al. 49th ICAAC

  8. Nuc-Sparing Combinations • Procedure: • Pts discontinued current regimen and started RAL 400 mg BID + ATV 400 mg QD • Results: • 27 people continued regimen for 36 weeks • 2 pts stopped after 8 weeks (1 had viral rebound on phenytoin, the other pt had elevated Cr) • 1 developed lung cancer after 36 weeks (vl <48) PJ Ruane, et al. 45th ICAAC

  9. Nuc-Sparing Combinations • ATZ [ ] were subtherapeutic in 4 pts (all had viral loads <48) • ITT analysis at week 24: • 27/29 (93%) had viral loads <400 • 24/29 (83%) had viral loads <48 • 7 pts had viremic blips from 48 to 83 copies • CD4 counts unchanged during follow up • TC and LDL fell significantly PJ Ruane, et al. 49th ICAAC

  10. ARV Management • BMS is conducting a dosing study using: • RAL 400 mg BID + ATZ 300 mg BID

  11. ARV Management • QD Raltegravir • RAL has long intracellular half-life (t ½ ~29 hours) • 311 patients with HIV RNA <50 replaced PIs with RAL • Based on drugs in background regimen, pts were placed on: • RAL 800mg QD vs RAL 400 mg BID Mena, et al. 49th ICAAC. Abstract H-920

  12. Mena, et al. 49th ICAAC. Abstract H-920

  13. ARV Management • Results: • Median Follow up was 15 months (range 9-30 months) • 5 pts discontinued RAL due to virologic failure • 1 in QD arm and 4 in the BID arm • All 5 had failed NRTIs in the past • 4 pts discontinued RAL for other reasons: • 1 voluntary withdrawal in the QD arm and 3 in the BID arm (poor adherence 2, H/A 1) • No difference in CD4 T cell gains Mena, et al. 49th ICAAC. Abstract H-920

  14. STARTMRK Trial 96 WEEKS Lennox J. et al. 49th ICAAC.

  15. STARTMRK Trial 96 WEEKS Lennox J. et al. 49th ICAAC.

  16. STARTMRK Trial 96 WEEKS Lennox J. et al. 49th ICAAC.

  17. STARTMRK Trial 96 WEEKS Lennox J. et al. 49th ICAAC.

  18. STARTMRK Trial 96 WEEKS Lennox J. et al. 49th ICAAC.

  19. Lennox J. et al. 49th ICAAC.

  20. STARTMRK Trial 96 WEEKS Lennox J. et al. 49th ICAAC.

  21. ARTEN STUDY 48 WEEKS Soriano, V. et al. 5th IAS

  22. ARTEN STUDY 48 WEEKS Soriano, V. et al. 5th IAS

  23. ARTEN STUDY 48 WEEKS Soriano, V. et al. 5th IAS

  24. ARTEN STUDY 48 WEEKS Soriano, V. et al. 5th IAS

  25. ARTEN STUDY 48 WEEKS Soriano, V. et al. 5th IAS

  26. New ARVs and Booster • GS-9350 is a potent, selective, CYP 3A inhibitor that lacks anti-HIV activity and has limited effects on adipocyte function in vitro • Other Properties: • Reduced potentials for off-target drug interactions due to enzyme inhibition or induction • Improved physiochemical properties over ritonavir, allowing tablet co-formulations with other agents • Boosts CYP 3A substrates comparable to ritonavir in humans L Xu, et al. 49th ICAAC.

  27. New ARVs and Booster L Xu, et al. 49th ICAAC.

  28. GS-9350 Ramanathan, et al. 49th ICAAC. Abstract A1-1301

  29. New ARVs • S/GSK 1349572 (572) was presented at IAS and showed great 10-day potency and higher barrier to resistance then RAL • Back up INI S/GSK 1265744 (744) displayed equal potency during and after 10 days of monotherapy • Long half life (~ 30 hours) • 10 days of 744 (30 mg QD) to ARV naïve pts lowered viral load by a median 2.6 log (range 3-1 log) • 7/8 had viral loads <50 at day 14 • No mutations to RAL or ELV emerged • Fatigue, H/A dizziness and indigestion affected 1 person • No serious or severe AEs including laboratory and EKG abnormalities Min S et al. 49th ICAAC. Abstract H-1228

  30. New Agents • INSPIRE Trial: Using IL-7 as a novel strategy for improving immune reconstitution in HIV • IL-7: • Critical factor for thymopoiesis, homeostasis and maturation of peripheral T-cells • Inhibits apoptosis of CD4 and CD8 T cells from HIV infected patients • Increases T cell counts in chronic HIV infected patients • Different from IL-2 in that it stimulates recent thymic emigrant, naïve, central and effector memory CD4 cells Y. Levy, et al. 49th ICAAC.

  31. IL-7 • Methods: • HIV infected pts with 101-400 CD4 cells and HIV RNA <50 while on ART received 3 weekly SQ injections of IL-7. • 3 doses vs placebo were tested • T cell subsets and thymopoiesis (RTE and sj/ß TRECs ratio quantification) analyses were performed Y. Levy, et al. 49th ICAAC.

  32. IL-7 Y. Levy, et al. 49th ICAAC.

  33. IL-7 Y. Levy, et al. 49th ICAAC.

  34. IL-7 Y. Levy, et al. 49th ICAAC.

  35. IL-7 • Conclusions: • 3 injection cycle of IL-7 induced a dose dependent and sustained increase in CD4 cells • Higher proportion of patients experienced CD4 counts >500 • Trend toward higher thymic output at 20mcg/kg dose • No clincial or laboratory side effects > grade 2 reported • 4 pts (in 20mcg/kg) had transient increases in HIV RNA Y. Levy, et al. 49th ICAAC.

  36. New ARVs Jacobson, J. 49th ICAAC. Oral Abstract.

  37. New ARVs Jacobson, J. 49th ICAAC. Oral Abstract.

  38. New ARVs Jacobson, J. 49th ICAAC. Oral Abstract.

  39. New ARVs Jacobson, J. 49th ICAAC. Oral Abstract.

  40. New ARVs Jacobson, J. 49th ICAAC. Oral Abstract.

  41. New ARVs Jacobson, J. 49th ICAAC. Oral Abstract.

  42. New ARVs Jacobson, J. 49th ICAAC. Oral Abstract.

  43. Jacobson, J. 49th ICAAC. Oral Abstract.

  44. New ARVs • MPC-42326 (Bevirimat dimeglumine) • New HIV class-maturation inhibitor • Prevents protease-mediated Gag cleavage at CA-SP1 • Good oral bioavailability and long half life (60 hours) • Active against drug resistant strains • Hypersensitive to protease resistant virus • Metabolized via glucuronidation (UGT1A3) • Not CYP 450 Bloch M, et al. 49th ICAAC

  45. New ARVs Bloch M, et al. 49th ICAAC

  46. New ARVs • Bevirimat • Effectiveness of drug depends on whether or not pts have polymorphisms on Gag • 501 Gag amino acids • 5 of these emerged as important determinants of response • Database sampling reveals that ~50% of pts have these polymorphisms • Use of this drug will require a genotype or phenotype prior to use (just like tropism testing) Bloch M, et al. 49th ICAAC

  47. New ARVs Bloch M, et al. 49th ICAAC

  48. New ARVs Bloch M, et al. 49th ICAAC

  49. New ARVs Bloch M, et al. 49th ICAAC

  50. New ARVs Bloch M, et al. 49th ICAAC

More Related