Transcript www.ukcab.net

Brian West: BHIVA Guidelines
What’s 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…
BHIVA Guidelines What’s 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)
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
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
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.
13%with VL<400; 23% vs. 9%<50
•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
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 VL>1000 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
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 Gazzard’s (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.
•Other new drugs under investigation
such as the CXCR4 and CCR5 antagonists are not
sufficiently advanced to be dealt with yet. (They’re
also not so well supported by Brian Gazzard!)
Thanks for your attention:
Brian West contact details:
[email protected]
Tel: 0131 558 3713