Brian West BHIVA Guidelines Whats new Guidelines published

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/3 TC O/D • Warn against combinations; ie Tenofovir/DDI…

BHIVA Guidelines What’s new: • Tenofovir/FTC in preference to AZT/3 TC, or even Kivexa? • New drugs since 2003; new ways to build 1 st combo? • Still NNRTI as support to Combivir/Truvada/Kivexa in 1 st 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 TMC 114 and Tipranavir, • The new RTI Reverset (D-D 4 FC) • The new NNRTI TMC 125

New Drugs: TMC 114 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 TMC 114/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 • RESIST 1 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, PL 14. 3 RESIST 2: phase 3 study, Glasgow 7 th 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 • 44 th 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: TMC 125 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 on 16 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 K 103 N • 1. Gazzard B et al. abstract 5, TMC 125, a Next-Generation NNRTI, Demonstrates High Potency after 7 Days Therapy in Treatment-Experienced HIV-1 -Infected Individuals with Phenotypic NNRTI Resistance. 9 th Conference on Retroviruses and Opportunistic Infections, Seattle, 2002. • 2. Gruzdev B et al. Abstract I-668. TMC 125 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 41 st Interscience Conference on Antimicrobial Agents and Chemotherapy; December 16 -19, 2001; Chicago, Ill.

• Other new drugs under investigation such as the CXCR 4 and CCR 5 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: brian. west@hivscotland. com Tel: 0131 558 3713