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: Indinavir/r (IDV/r; Crixivan)

Last updated on Sep 07, 2007
Key Mutations
Major IDV-selected
V82A/T/F/S/M
M46I/L
I54V/T//A
I84V
L90M
Many different protease mutations have been reported in patients receiving IDV (Belec et al. 2000; Condra et al. 1996; Descamps et al. 2005; Gallego et al. 2001). This may be due in part to the nature of the drug or to the fact that IDV was initially frequently used in suboptimal treatment regimens.

V82A/T/F/S and less commonly L90M and I84V occur in patients developing virological failure while receiving an IDV-containing regimen. Alone these mutations reduce susceptibility about 2-fold. In combination with a mutation at positions 46 or 54, these mutations are associated with bout 10-fold IDV-reduced susceptibility (Rhee et al. 2006). V82M has been reported commonly in subtype G isolates from persons receiving IDV(Camacho et al. 2005)
 
Additional IDV-selected
V32I
I47V
G48V
L76V
N88S
V32I, I47V, G48V, L76V, and N88S each occur in a small proportion of patients receiving IDV failure and cause low-level IDV resistance (Belec et al. 2000; Condra et al. 1996; Descamps et al. 2005; Gallego et al. 2001; Rhee et al. 2006).
 
Accessory
L24I
F53L
G73S/T/C/A
L24I, F53L, and G73S/C/T/A are selected by IDV and contribute to reduced IDV susceptibility (Belec et al. 2000; Condra et al. 1996; Descamps et al. 2005; Gallego et al. 2001). (Rhee et al. 2005; Rhee et al. 2006).
 
Clinical Uses
Initial therapy
IDV/r is not listed by the US DHHS or IAS-USA Guidelines as an option for initial HAART. Although it is highly active virologically, it has bas been associated with higher rate of toxicity than most other boosted PIs (Bongiovanni et al. 2004; Boyd et al. 2006; Burger et al. 2003; Canestri et al. 2007; Duvivier et al. 2003; Rockstroh et al. 2000; Voigt et al. 2002; Young et al. 2002).
 
Salvage therapy
IDV/r should not ordinarily be used for salvage therapy because it has generally not performed as well in clinical trials as have LPV/r, TPV/r, and DRV/r (Cahn et al. 2006; Clotet et al. 2007; Dragsted et al. 2003; Gathe et al. 2006; Haubrich et al. 2007; Hicks et al. 2006; Katlama et al. 2007).

Fold-reductions of 2-fold in the PhenoSense assay have been associated with reduced virologic response and fold reductions of 10-fold have been associate with near complete loss of virologic response . The activity of IDV as a salvage PI often depends on pharmacokinetic factors rather than presence of specific PI-resistance mutations (Campo et al. 2003; Casado et al. 2000; Shulman et al. 2002).
 
References
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  • Campo, R.E., J.N. Moreno, G. Suarez, N. Miller, M.A. Kolber, D.J. Holder, M. Shivaprakash, D.M. DeAngelis, J.L. Wright, W.A. Schleif, E.A. Emini, and J.H. Condra. 2003. Efficacy of indinavir-ritonavir-based regimens in HIV-1-infected patients with prior protease inhibitor failures. Aids 17: 1933-1939.
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  • Casado, J.L., A. Moreno, R. Sabido, P. Marti-Belda, A. Antela, F. Dronda, M.J. Perez-Elias, and S. Moreno. 2000. A clinical study of the combination of 100 mg ritonavir plus 800 mg indinavir as salvage therapy: influence of increased plasma drug levels in the rate of response. HIV Clin Trials 1: 13-19.
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  • Dragsted, U.B., J. Gerstoft, C. Pedersen, B. Peters, A. Duran, N. Obel, A. Castagna, P. Cahn, N. Clumeck, J.N. Bruun, J. Benetucci, A. Hill, I. Cassetti, P. Vernazza, M. Youle, Z. Fox, and J.D. Lundgren. 2003. Randomized trial to evaluate indinavir/ritonavir versus saquinavir/ritonavir in human immunodeficiency virus type 1-infected patients: the MaxCmin1 Trial. J Infect Dis 188: 635-642.
  • Duvivier, C., A. Myrto, A.G. Marcelin, J. Ghosn, H. Ait-Mohand, L. Schneider, R. Agher, F. Bricaire, D. Costagliola, V. Calvez, G. Peytavin, and C. Katlama. 2003. Efficacy and safety of ritonavir/indinavir 100/400 mg twice daily in combination with two nucleoside analogues in antiretroviral treatment-naive HIV-infected individuals. Antivir Ther 8: 603-609.
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  • Shulman, N., A. Zolopa, D. Havlir, A. Hsu, C. Renz, S. Boller, P. Jiang, R. Rode, J. Gallant, E. Race, D.J. Kempf, and E. Sun. 2002. Virtual inhibitory quotient predicts response to ritonavir boosting of indinavir-based therapy in human immunodeficiency virus-infected patients with ongoing viremia. Antimicrob Agents Chemother 46: 3907-3916.
  • Voigt, E., A. Wickesberg, J.C. Wasmuth, P. Gute, L. Locher, B. Salzberger, A. Wohrmann, A. Adam, L. Weitner, and J.K. Rockstroh. 2002. First-line ritonavir/indinavir 100/800 mg twice daily plus nucleoside reverse transcriptase inhibitors in a German multicentre study: 48-week results. HIV Med 3: 277-282.
  • Young, B., M.A. Fischl, H.M. Wilson, T.S. Finn, E.H. Jensen, M.J. DiNubile, and R.K. Zeldin. 2002. Open-label study of a twice-daily indinavir 800-mg/ritonavir 100-mg regimen in protease inhibitor-naive HIV-infected adults. J Acquir Immune Defic Syndr 31: 478-482.