Stanford University HIV Drug Resistance Database - A curated public database designed to represent, store, and analyze the divergent forms of data underlying HIV drug resistance.

Antiretroviral drug summary: Delavirdine (DLV; Rescriptor)

Last updated on Sep 24, 2007
Key Mutations
Major
K103N/S
Y181C/I/V
P236L

Accessory
Y188L/H/C
V106A/M
L100I
K101E/P
A98G
V108I
V179D/E
M230L
K238T/N

Potential Cross-Resistance
E138K
V179F
F227C
Y318F
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.
 
Clinical Uses
Initial therapy
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).
 
Salvage therapy
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.
 
References
  • Ceccherini-Silberstein, F., V. Svicher, T. Sing, A. Artese, M.M. Santoro, F. Forbici, A. Bertoli, S. Alcaro, G. Palamara, A. d'Arminio Monforte, J. Balzarini, A. Antinori, T. Lengauer, and C.F. Perno. 2007. Characterization and Structural Analysis of Novel Mutations in HIV-1 Reverse Transcriptase Involved in the Regulation of Resistance to Non-Nucleoside Inhibitors. J Virol.
  • Hammer, S.M., M.S. Saag, M. Schechter, J.S. Montaner, R.T. Schooley, D.M. Jacobsen, M.A. Thompson, C.C. Carpenter, M.A. Fischl, B.G. Gazzard, J.M. Gatell, M.S. Hirsch, D.A. Katzenstein, D.D. Richman, S. Vella, P.G. Yeni, and P.A. Volberding. 2006. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel. Jama 296: 827-843.
  • Rhee, S.Y., J. Taylor, G. Wadhera, A. Ben-Hur, D.L. Brutlag, and R.W. Shafer. 2006. Genotypic predictors of human immunodeficiency virus type 1 drug resistance. Proc Natl Acad Sci U S A 103: 17355-17360.
  • US DHHS Panel, A. 2006. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (The living document, October, 2006), http://aidsinfo.nih.gov/.