Delavirdine resistant clinical isolates remained susceptible to PNU142721 and DMP266.
Originally Published on August 3, 1999
Wathen L, Freimuth W, Sharp T, Ruzicka K.
6th Conference on Retroviruses and Opportunistic Infections. 31 Jan-4 Feb, 1999, Chicago, IL. Abstract 111.
ABSTRACT:
There is limited knowledge about whether use of one non-nucleoside reverse transcriptase inhibitor precludes the use of a second later in therapy. Viral isolates from 22 highly nucleoside experienced patients treated 6-95 weeks with ZDV+DLV or ZDV+DLV+ddI/ddC were tested in vitro for susceptibility to DLV (delavirdine, RESCRIPTOR), DMP 266 (efavirenz, SUSTIVA) and an experimental third generation NNRTI (PNU142721). The mean DLV IC50 was 11然 (range 0.3-50然), with the great majority (>70%) above 3.0 然. The isolates had multiple mutations (range=1-16, mean=9) in the reverse transcriptase gene with the predominant substitution being the K103N.
Both DMP 266 and PNU142721 were able to inhibit the p24 production from these isolates with sub-micromolar concentrations averaging 0.0345 然 for DMP 266 and 0.0235然 for U-142721. It is particularly important to note that in addition to the antiviral activity of DMP
266 against these K103N containing isolates, there is also susceptibility demonstrated in the isolates harboring P236L (isolates 174 and 402). It appears that the majority of DLV resistant clinical isolates remained susceptible to DMP 266 and PNU142721. In addition, the drug concentrations needed to suppress viral replication in these isolates are attainable in vivo. This strongly suggests that treating patients with delavirdine and later switching them to another NNRTI containing regimen will be possible.
