Antiretroviral drug summary: Delavirdine (DLV; Rescriptor)
Last updated on Sep 24, 2007
Since DLV is not used for initial therapy and rarely used for salvage therapy, there are few studies describing the mutations emerging during DLV treatment. These studies suggest that K103N, Y181C, and P236L are the most common mutations DLV-selected mutations. Each reduces DLV susceptibility about 50-fold, although the precise reduction in susceptibility on other NNRTI resistance mutations and several common polymorphic mutations that synergistically reduce susceptibility (Ceccherini-Silberstein et al. 2007; Rhee et al. 2006).
However, nearly all NNRTI-associated mutations, even those not reported to have been selected by DLV are likely to be associated with clinically significant reduced susceptibility with several exceptions: (i) G190A/S are associated with increased DLV susceptibility. Anecdotal case reports have suggested that this may provide a clinical benefit in some patients. However, the fact that NNRTI use often leads to the selection of multiple NNRTI-resistance variants including some as minor variants suggests that not all patients with these mutations will benefit from DLV treatment. The effects of other mutations at position 190 are more variable. For example, the third most common mutation, G190E is associated with intermediate DLV resistance. (ii) Mutations at position 188 generally have a greater phenotypic effect on NVP and EFV than on DLV, although the magnitude of the difference and the unreliable pharmacokinetics of DLV make this observation unlikely to be clinically relevant. (iii) P225H and F227L are each associated with increased DLV susceptibility. However, the fact that these mutations are accessory mutations that are nearly always associated with other NNRTI mutations such as K103N and V106A make this observation unlikely to be clinically relevant.
The US DHHS and IAS-USA Guidelines do not recommend DLV as a preferred or alternative NNRTI for initial therapy (Hammer et al. 2006; US DHHS Panel 2006).
The US DHHS and IAS-USA Guidelines do not recommend DLV for use as second-line therapy (Hammer et al. 2006; US DHHS Panel 2006). Anecdotal reports suggest that DLV may be useful in treating some patients with viruses that contain the mutations G190A or G190S with no other NNRTI-resistance mutations or in pharmacokinetic boosting of PIs in patients that cannot receive RTV.