Delavirdine (DLV)

Delavirdine a synthetic antiretroviral agent, is a nonnucleoside reverse transcriptase inhibitor.Delavirdine differs structurally from nevirapine, a dipyridodiazepinone derivative nonnucleoside reverse transcriptase inhibitor. The drug inhibits replication of HIV-1 by interfering with viral RNA- and DNA-directed polymerase activities of reverse transcriptase. The mechanism of action of DLV derivatives appears to be similar to that of other nonnucleoside reverse transcriptase inhibitors (e.g., nevirapine, loviride, efavirenz). All nonnucleoside reverse transcriptase inhibitors appear to bind to a common region of reverse transcriptase and exhibit similar kinetic characteristics in their mode of retroviral inhibition.

Spectrum: Delavirdine is a highly specific antiretroviral agent with a very limited spectrum of activity. The drug has in vitro virustatic activity against HIV-1, but is inactive against HIV-2.

Resistance: Strains of HIV-1 with reduced susceptibility to delavirdine (i.e., 10- to 100-fold decrease in susceptibility from baseline) have been produced in vitro by serial passage of the retrovirus in the presence of increasing concentrations of the drug. The mechanism of resistance or reduced susceptibility to delavirdine has not been fully determined, but mutation of HIV reverse transcriptase appears to be involved.

Clinical Uses: Oral delavirdine is used in combination with other antiretroviral agents for the management of human immunodeficiency virus type 1 (HIV-1) infection in adults.

Adverse reactions: Rash is the major toxicity associated with delavirdine therapy. Severe or life- threatening rash (e.g., erythema multiforme, Stevens-Johnson syndrome) have been reported rarely and resolved after the drug was discontinued. Rash usually is evident within 1-3 weeks (median: 11 days) following initiation of delavirdine therapy and typically is diffuse, maculopapular, erythematous, and often pruritic; rash occurs mainly on the upper body and proximal arms with decreasing intensity of the lesions on the neck and face and progressively less on the rest of the trunk and limbs.