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: Nelfinavir (NFV; Viracept)

Last updated on Sep 07, 2007
Key Mutations
Major NFV-selected
D30N ± N88D
In patients developing NFV resistance while receiving NFV, there are three distinct non-overlapping patterns of PI resistance mutations: D30N±N88D, L90M, and N88S (Atkinson et al. 2000; Patick et al. 1998; Patick et al. 1996; Walmsley et al. 2001); (Deforche et al. 2006; Kempf et al. 2004; Mitsuya et al. 2006; Shafer et al. 2003). M46I/L may occur alone or with any of the 3 mutation patterns.

D30N occurs more commonly than L90M and N88S in subtype B but not in all other subtypes. L90M occurs more commonly in subtype C (Abecasis et al. 2005; Cane et al. 2001; Grossman et al. 2004). N88S has been reported more commonly in subtype AE (Ariyoshi et al. 2003).
Mutations at positions 48, 54, 82, and 84 rarely occur in patients receiving NFV as their initial PI. By themselves, they cause low-level phenotypic resistance. But in combination with other mutations, they are associated with high-level resistance and lack of virological response (Rhee et al. 2006).
L23I is a rare NFV-selected mutation which occurs in <1% of NFV treated patients (Johnston et al. 2004). L23I is in the protease substrate cleft and by itself reduces NFV susceptibility by several fold.

L33F and G73S/T/C/A are selected by NFV and decrease NFV susceptibility (Rhee et al. 2005; Rhee et al. 2006).

In contrast to ritonavir-boosted PIs, many polymorphic mutations including those at positions 10, 20, 36, 71, and 77 may be associated with decreased NFV susceptibility and virological responsiveness even in the absence of major PI-resistance mutations (Perno et al. 2001).

Several additional mutations including T74S and L89IV may be more commonly associated with NFV resistance in several non-B subtypes (Abecasis et al. 2005; Deforche et al. 2006)
Clinical Uses
Initial therapy
The US DHHS and IAS-USA Guidelines list NFV as an alternative, rather than preferred option for PI-based initial ARV therapy because the combination of two NRTIs + NFV has a significantly higher failure rate than two NRTIs + NVP, EFV, LPV/r or other RTV-boosted PIs (Kempf et al. 2004; Podzamczer et al. 2002; Shafer et al. 2003; Walmsley et al. 2002).
Salvage therapy
Because most PI-resistance mutations reduce NFV susceptibility and because NFV has a low genetic barrier to resistance, NFV is not a recommended PI for salvage therapy (Dronda et al. 2001; Lawrence et al. 1999; Walmsley et al. 2001).
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