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

V32I, M46I/L, I47V, I50V, I54M/L, and I84V are the most common mutations to develop during in vitro passage with APV and in patients developing virologic failure while receiving APV or FPV containing regimens (Ait-Khaled et al. 2003; MacManus et al. 2003; Maguire et al. 2002; Murphy et al. 1999; Partaledis et al. 1995; Prado et al. 2002; Smith et al. 2006).

By themselves, I50V, I54M/L, and I84V have the greatest effect on APV susceptibility reducing it about 8-fold, 4-fold, and 4-fold respectively (Murphy et al. 2004; Parkin et al. 2003; Rhee et al. 2006).

I54V/A/T/S, V82A/T/F/S, and L90M rarely occur during APV or FPV failure. However, these mutations, which occur commonly with other PIs confer low-to-intermediate cross resistance to APV and FPV (Duval et al. 2002; Lastere et al. 2004; Marcelin et al. 2007; Marcelin et al. 2003; Masquelier et al. 2006; Pellegrin et al. 2007; Rhee et al. 2006; Schmidt et al. 2000).

L33F and to a lesser extent V11I and L89V are associated with decreased APV susceptibility (Kozal et al. 2006; Prado et al. 2002; Rhee et al. 2006).

N88S increases APV susceptibility in vitro and potentially in vivo (Masquelier et al. 2006; Ziermann et al. 2000).

FPV is a pro-drug of amprenavir (APV). Much of the knowledge on the genetic mechanisms of FPV resistance are based in part on in vitro and in vivo APV data. APV is the drug used for susceptibility testing.

The US DHHS and IAS-USA Guidelines list FPV/r as a preferred PI for initial HAART. In contrast to APV, APV/r, and FPV, virologic failure in patients receiving FPV/r has not been associated with PI resistance (Eron et al. 2006; Gathe et al. 2004; Smith et al. 2006). Moreover, FPV/r has had similar efficacy to LPV/r (Eron et al. 2006) and ATV/r (Smith et al. 2006) in previously untreated patients.

FPV/r does not have the same track record as LPV/r, TPV/r, or DRV/r for salvage therapy (Cahn et al. 2006; Clotet et al. 2007; Gathe et al. 2006; Haubrich et al. 2007; Hicks et al. 2006; Katlama et al. 2007).

FPV/r has a relatively low genetic barrier to resistance: loss of clinical activity begins with 2-fold decreases in susceptibility and near complete loss of clinical activity occurs at about 10-fold decreased susceptibility .

FPV has a similar resistance profile to DRV (Parkin et al. 2007)but because DRV/r has a higher genetic barrier to resistance (Coakley et al. 2007 ), there are likely to be few situations in which FPV/r is the optimal salvage therapy PI.