Question:
Does the conference give any indication that any future protease inhibitors
would be effective AFTER a patient has failed on other protease inhibitors (e.g.
ritonavir) due to resistance. In other words is there and firm information on
future protease inhibitors which have a different resistance profile to the
ones currently used. Also is there any information on future reverse transcriptase
inhibitors which have a different resistance profile to the old ones e.g. AZT
and DDI?
THANKS for taking the time to answer.
Dr. Torres' Response:
At the Retrovirus conference, several presentations on protease inhibitors
focuses on the patterns of cross resistance that these drugs have exhibited
both in vitro and in vivo. Use of Nelfinavir for example leads to the
emergence of a codon mutation 30, which does not confer cross-resistance to
ritonavir, indinavir yet can have some cross-resistance with saquinavir.
Saquinavir leads to a mutation codon 90 which can lead to cross-resistance
to indinavir in 30-40% after a year when used in combination with nucleoside
analogs. Indinavir and ritonavir can lead to multiple mutations which can
lead to cross resistance to all the other protease inhibitors. In terms of
RT inhibitors, the new drug by Glaxo Wellcome, 1592U89 does not seem to lead
to the emergence of resistant virus and various cases were shown, where AZT
and ddI resistance virus was inhibited by 1592U89.
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