Isolates carrying the Y181C or K103N mutation have a 30-fold increase in IC50 to delavirdine compared to wild-type isolates. The P236L mutation leads to a 70-fold increase in IC50, while the combination of Y181C/P236L yields the highest degree of resistance (>200-fold increase in IC50).
Cross-resistance:
Isolates carrying the P236L mutation remain susceptible to other NNRTIs (efavirenz, nevirapine). Isolates carrying the Y181C mutation are resistant to nevirapine but susceptible to efavirenz. Although it is generally accepted that isolates carrying the K103N mutation are resistant to all NNRTIs, recent in vitro data suggest that some delavirdine-resistant viruses with this mutation may remain susceptible to efavirenz. These observations must be confirmed before their clinical significance can be determined.
Emergence of resistance in vivo:
This occurs rapidly in subjects receiving delavirdine therapy in the absence of maximal virologic suppression. The P236L mutation is rarely observed, while the K103N and Y181C mutations (alone or in combination) are almost always present.
Clinical correlates of resistance:
If therapy is continued in the presence of drug resistance, a rapid rebound in plasma viral load is observed, followed by a progressive decrease in CD4 cell counts.
Other comments:
Although the addition of the Y181C mutation in a zidovudine resistance background was shown to restore zidovudine susceptibility in vitro, the clinical correlation of this observation remains uncertain.
Desire N, Amiel C, Schneider V, Delphin N, E Dam, Clavel F, Nicolas JC, Rozenbaum W.
An HIV-1 isolate with the mutation G190E and an insertion between codons 100-105 of reverse transcriptase: phenotypic resistance implications.Antiviral Ther 2002; 7:S35.
Delavirdine (DLV), Rescriptor
