1 / 11

Managing Early Antiretroviral Failure: Easy Answers for the Busy Clinician—Not!

Managing Early Antiretroviral Failure: Easy Answers for the Busy Clinician—Not!. Joseph J. Eron, Jr, MD. JJ Eron, JR, MD. Presented at IAS –USA /RWCA Clinical Conference, August 2004. The International AIDS Society–USA.

zuwena
Download Presentation

Managing Early Antiretroviral Failure: Easy Answers for the Busy Clinician—Not!

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. Managing Early Antiretroviral Failure: Easy Answers for the Busy Clinician—Not! Joseph J. Eron, Jr, MD JJ Eron, JR, MD.Presented at IAS–USA/RWCA Clinical Conference, August 2004. The International AIDS Society–USA

  2. GS 903 Study: Week-144 Virologic Outcomes of Tenofovir DF vs Stavudine + 3TC/EFV Intent to Treat (Missing = Failure) 100 80 73% 69% 60 Patients with HIV-1 RNA < 50 copies/mL (%) 40 TDF + 3TC + EFV 20 d4T + 3TC + EFV 0 0 24 48 72 96 120 144 Weeks Gallant et al. Abstract TuPeB4538.

  3. Duration of Initial Therapy The first regimen will be time-limited Chen et al 9th CROI

  4. First Salvage: After 1st Rx • Most virologic failure is not clinical or immunologic failure • Frequently virologic failure is not regimen failure • Most regimen failure is not due to broad resistance

  5. Virologic FailureDoes Not Equal Immune or Clinical DeclineFrench Cohort (N=2236): 100 95 IR+/VR+ IR+/VR- 90 IR-/VR+ Percent alive and AIDS-free 85 IR-/VR- 80 75 6 12 18 24 30 . Months since introduction of PI Grabar, et al, Ann Intern Med 2000

  6. Patterns of Virologic Failure Limited response HIV RNA level Rebound Blip Sustained low level viremia Re-suppression Suppression Time

  7. First Failure and Resistance • HIV-1 Resistance may be limited • 20-50% of patients may have HIV-1 with no evidence of resistance • If present, resistance usually arises to more potent components of the regimen with low genetic barrier • 3TC • NNRTI • Nelfinavir • Resistance to enhanced PI may be very limited

  8. Initial Resistance NNRTI-based Regimens • NNRTI resistance mutations • 45 to 80% of early failures • 3TC resistance • 30-50% of early failures • Other resistance mutations (e.g. TAMs, K65R) • < 10%

  9. PI Resistance • PI mutations uncommon in early virologic failure • Some primary PI mutations not associated with cross-resistance eg, D30N (NFV), I50L (ATV) • Others associated with cross-resistanceeg, 82, 84, 90 (LPV/RTV, IDV, SQV) • Accumulation of secondary mutations associated with increasing cross-resistance

  10. Resistance Mutations with Boosted vs Unboosted Fosamprenavir * Excluding common natural polymorphisms observed in absence of other RT or PR mutations Macmanus S et al. 10th CROI, Boston, 2003, Abstract 598.

  11. After 1st Rx • Summary • Most virologic failure is not clinical or immunologic failure • Most virologic failure is not regimen failure • Assess causes of virologic failure • Most regimen failure not due to broad resistance • Nucleoside resistance extremely important • Second line therapy should be more successful than observed in studies to date

More Related