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: Atazanavir/r (ATV/r; Reyataz)

Last updated on Nov 10, 2008
Key Mutations
Major ATV-selected
I50L
N88S
I50L is the most common protease mutation to develop in PI-naive patients with virologic failure while receiving unboosted ATV. I50L reduces ATV susceptibility by ~8-fold (Weinheimer et al. 2005). I50L occurs less frequently in patients receiving ATV/r or in previously PI-treated patients receiving ATV (Colonno et al. 2004; Malan et al. 2008; McGrath et al. 2006; Zolopa et al. 2007).

N88S is one of the mutations to emerge in vitro when HIV-1 is cultured in the presence of increasing ATV concentrations and has been reported in patients developing virologic failure with ATV/r (Coakley et al. 2005; Gong et al. 2000) It reduces ATV susceptibility ~10-fold (Coakley et al. 2005; McGrath et al. 2006; Rhee et al. 2006; Zolopa et al. 2007).
 
Cross-resistance
V32I
G48V/M
F53L
I54V/L/M/T/A
G73S/C/T/A
I84V/A/C
L90M
These mutations have generally not been reported in patients receiving ATV or ATV/r. However, they have been associated with reduced ATV susceptibility and reduced virological responses to an ATV/r containing salvage therapy regimen (Bertoli et al. 2006; Marcelin et al. 2006; Naeger and Struble 2006; Pellegrin et al. 2006; Rhee et al. 2006; Vermeiren et al. 2007; Vora et al. 2006).

G73S/T/C/A occurs frequently in patients developing virologic failure while receiving unboosted ATV and have been associated with decreased ATV susceptibility and decreased virologic response to an ATV or ATV/r containing regimen (Colonno et al. 2004; Malan et al. 2008; Rhee et al. 2006; Vermeiren et al. 2007).

G48M and I84A/C are rare mutations associated with high-levels of resistance to multiple PIs including LPV (Mo et al. 2007; Vermeiren et al. 2007).
 
Accessory
D30N+N88D
L33F
M46I/L
V82A/T/F/S
D30N+N88D have been associated with a 2-fold to 4-fold decrease in ATV susceptibility (Di Giambenedetto et al. 2008; Rhee et al. 2006; Vermeiren et al. 2007). L33F has been selected by ATV in vitro and is associated with reduced ATV susceptibility (Gong et al. 2000; Rhee et al. 2006; Zolopa et al. 2007).
 
Hypersusceptibility
L76V increases ATV susceptibility.
 
Clinical Uses
Initial therapy
The U.S. DHHS and IAS-USA guidelines recommend ATV/r as a preferred PI for initial HAART based on its tolerability and apparent equivalency to LPV/r and FPV/r in previously untreated persons (Hammer et al. 2008; Molina et al. 2008; Smith et al. 2008; US Department of Health and Human Services Panel on Clinical Practices for Treatment of HIV Infection 2008). Like other boosted PIs, virological failure has generally not been associated with the selection of PI resistance mutations suggesting that failure has generally resulted from nonadherence (Malan et al. 2008; Smith et al. 2008).
 
Salvage therapy
ATV/r should not ordinarily be used for salvage therapy because it has not performed as well in clinical trials as have LPV/r, TPV/r, DRV/r (Clotet et al. 2007; Cohen et al. 2005; Johnson et al. 2005; Katlama et al. 2007; Naeger and Struble 2006) and because the genetic barrier to resistance is low with decreased virological responses occurring in viruses with 2-fold decreased susceptibility and nearly complete loss of response in viruses with 5-fold or higher decreased susceptibility (Coakley et al. 2006; Winters et al. 2008). ATV/r may be useful in patients who failed previous PI-containing regimens because of non-adherence.
 
References
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