Scottsdale, Arizona: At the Fifth International Workshop on HIV Drug Resistance and Treatment Strategies, which opened under the Arizona sun this morning, the 250 delegates heard new data on several experimental antiretrovirals which, it is hoped, will prove effective against the drug resistant viruses which many people with prior treatment experience now harbour.
Several of these new therapies are in very early stages of development and have yet to reach human trials. If their progress is successful, which cannot be guaranteed at this point, broader access is unlikely before the end of 2002. Entry inhibitors from Trimeris/Roche are placed further along the pipeline. Two drugs in this class, T-20 and T-1249, are in human trials, and target HIV as it fuses with immune cells. Using Virco’s Antivirogram, a phenotypic resistance test, the Trimeris/Roche team demonstrated that both drugs remained active against a panel of 86 HIV sample strains, over half of which were resistant to all three currently available drug classes (Sista, Miralles).
For Du Pont, Lee Bacheler presented in vitro data on their two experimental PIs, DPC 681 and DPC 684. Against a panel of 30 PI resistant recombinant viruses, the two DPC compounds displayed the lowest levels of phenotypic resistance relative to other currently marked PIs. Du Pont estimate that drug levels of 0.7 micromolar in the case of DPC 684, and 1 micromolar for 681, will produce effective suppression of PI resistant viruses. According to Bacheler, animal studies suggest these levels will be achievable in humans, and research is ongoing.
TMC120 and TMC125 are second generation NNRTIs from Tibotec/Virco. According to researchers, when passaged against a laboratory strain, resistance to the TMC compounds emerged either more slowly, or not at all, compared to efavirenz and nevirapine, the two NNRTIs in common use at present (de Bethune).
The next event in NAM’s Clinical Symposia Programme offers feedback from the Resistance Workshop with speakers including Charles Boucher, Jonathan Schapiro, Deenan Pillay and Francois Clavel. Registration for this special event, which takes place in London on June 29th and is run in partnership with the European AIDS Treatment Group, is free. For more information contact keith@nam.org.uk
Sista P et al. The fusion inhibitors T-20 and T-1249 demonstrate potent in vitro antiviral activity against clade B HIV-1 isolates resistant to reverse transcriptase and protease inhibitors and non-B clades. Antiviral Therapy 2001; 6(Supplement 1):3.
Miralles GD et al. Baseline genotype and prior antiretroviral history do not affect virological response to T-1249. Antiviral Therapy 2001; 6(Supplement 1):4.
Bacheler LT et al. Resistance profiles of second generation HIV protease inhibitors DPC 681 and DPC 684. Antiviral Therapy 2001; 6(Supplement 1):5.
de Bethune M-P et al. In vitro selection experiments demonstrate reduced development of resistance with TMC120 and TMC125 compared with first generation non-nucleoside reverse transcriptase inhibitors. Antiviral Therapy 2001; 6(Supplement 1):6.