A curated public database designed to represent, store, and analyze the divergent forms of data underlying HIV drug resistance.

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. 2006; 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).

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; Vora et al. 2006).

V32I has been selected by ATV in vitro (Gong et al. 2000). V32I, I47V, and G48V have been associated with decreased ATV susceptibility (Rhee et al. 2006).

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

I50L increases HIV-1 susceptibility to most other PIs. L76V increases ATV susceptibility.

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 (Malan et al. 2006; Smith et al. 2006). 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. 2006; Smith et al. 2006).

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. 2007).