Guidelines published as an update on 2003 guidelines. About 89 pages. New data only

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Brian West BHIVA Guidelines Whats new

• Guidelines published as an update on 2003
  guidelines. About 8-9 pages. New data only
• Look at new backbones of therapy?
• Tenofovir/FTC O/D
• New combinations of drugs ie Abacavir/3TC O/D
• Warn against combinations ie Tenofovir/DDI

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BHIVA Guidelines Whats new

• Tenofovir/FTC in preference to AZT/3TC, or even
  Kivexa?
• New drugs since 2003 new ways to build 1st
  combo?
• Still NNRTI as support to Combivir/Truvada/Kivexa
  in 1st line, or maybe Fosamprenavir/Reyataz?
  (Importance of resistance testing)
• Emphasise that all PIs to be boosted? (Unlike US)

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BHIVA Guidelines, New Drugs

• Presently deals with drugs now in use such as
  Enfuvirtide, Atazanavir, Tenofovir
• New drugs to be looked at include the new PIs
  TMC114 and Tipranavir,
• The new RTI Reverset (D-D4FC)
• The new NNRTI TMC125

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New Drugs TMC114 a new boosted PI

• Shown to be effective in a PI experienced
  population with resistant virus
• 50 people randomised. After 8 weeks of treatment
  the median difference in VL and absolute drop in
  VL among people switching to TMC114/RTV
  significantly exceeded VL changes in people
  staying with the same PI
• Monika Peeters CROI 2004 abstract 533

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New Drugs Tipranavir a new boosted PI

• RESIST1 and RESIST 2 Different continents
  similar results - promising
• Evaluated the efficacy and safety of
  TPV/Ritonavir(RTV) in comparison to 4 different
  RTV-boosted PIs
• People with multiple PI resistance mutations had
  better virological outcomes on Tipranavir 34 vs.
  13with VLlt400 23 vs. 9lt50
• Expanded access in UK. Launched this year
• Pedro Cahn Foundación Huesped, Buenos Aires,
  Argentina, PL14.3 RESIST 2 phase 3 study,
  Glasgow 7th International Congress on Drug
  Therapy in HIV Infection

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New Drugs Reverset a new RTI

• Low mitochondrial toxicity O/D drug
• May have activity against many viral strains with
  NRTI resistance
• 10 day trial Small numbers 10 treatment
  experienced people with VLgt1000 enrolled. 2 given
  placebo
• 7/8 had VL drop of at least 0.5 log 4 with VL
  below 400. Next phase sees 180 recruited
• 44th ICAAC (Slide H-1130) Tolerance and
  anti-HIV-1 activity of Reverset following 10 days
  as add-on therapy to current regimens in
  treatment experienced HIV-infected individuals
  RL Murphy et al

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New Drugs TMC125 a new NNRTI

• Drugs in this class have problems with cross
  resistance
• TMC 125 could be used against viral strains with
  NNRTI resistance
• Brian Gazzards (1) 7 day substitution study on16
  people with efavirenz resistance showed at day 7,
  the median decrease in viral load was -0.9 log
  from baseline
• In vitro data from CROI 2001 (2) showed high
  activity against key resistant strains such as
  K103N
• 1.Gazzard B et al. abstract 5, TMC125, a
  Next-Generation NNRTI, Demonstrates High Potency
  after 7 Days Therapy in Treatment-Experienced
  HIV-1-Infected Individuals with Phenotypic NNRTI
  Resistance. 9th Conference on Retroviruses and
  Opportunistic Infections, Seattle, 2002.
• 2.Gruzdev B et al. Abstract I-668. TMC125 is a
  highly potent non-nucleoside reverse
  transcriptase inhibitor (NNRTI) in antiretroviral
  therapy (ART)-naive, HIV-1 infected subjects. In
  Program and abstracts of the 41st Interscience
  Conference on Antimicrobial Agents and
  Chemotherapy December 16-19, 2001 Chicago, Ill.
  

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Other new drugs under investigationsuch as the
CXCR4 and CCR5 antagonists are not sufficiently
advanced to be dealt with yet. (Theyre also not
so well supported by Brian Gazzard!)Thanks for
your attention Brian West contact
detailsbrian.west_at_hivscotland.comTel 0131 558
3713