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

G48V is selected by SQV both in vitro by SQV and in vivo G48V reduces SQV susceptibility ~10-fold (Jacobsen et al. 1996; Jacobsen et al. 1995; Marcelin et al. 2004; Schapiro et al. 1999; Sevin et al. 2000; Zolopa et al. 1999). By itself it reduces SQV susceptibility about 10-fold (Rhee et al. 2006) and should be considered a contraindication to SQV and SQV/r. G48M is a PI-associated mutation that appears to have an effect similar to G48V (King et al. 2007; Parkin et al. 2003; Rhee et al. 2005).

L90M is the most commonly occurring SQV-resistance mutation in patients receiving unboosted SQV (Schapiro et al. 1999; Schapiro et al. 1996; Sevin et al. 2000; Zolopa et al. 1999).

I84V and less commonly I84AC have been reported in combination with L90M primarily in persons developing virologic failure while receiving SQV/r (Mo et al. 2006). I84V + L90M reduces SQV susceptibility 10-20-fold (Rhee et al. 2006).

In combination with other mutations, I54VT reduce SQV susceptibility and its in vivo activity (Harrigan et al. 1999; Marcelin et al. 2004; Zolopa et al. 1999). Although M46I/L and V82A do not reduce SQV susceptibility, these mutations have been associated with a reduced virologic response to SQV/r possibly because they are markers for other PI-resistance mutations (Harrigan et al. 1999; Marcelin et al. 2004; Zolopa et al. 1999). in combination with other mutations, they decrease SQV susceptibility .

G73S is particularly important when it occurs in combination with L90M. Although L90M alone reduces SQV susceptibility 1 to 5 fold. but in combination with G73S it reduces SQV susceptibility about 10-fold (Rhee et al. 2006). F53L is selected by SQV and associated with decreased SQV susceptibility (Rhee et al. 2006). L24I is not selected by SQV but is associated with decreased SQV susceptibility and virologic responses in multivariate analyses (Marcelin et al. 2004; Rhee et al. 2006).

L76V increases SQV susceptibility.

The US DHHS Guidelines lists SQV/r as an alternative PI for initial PI-based HAART. The IAS-USA Guidelines lists SQV/r as a preferred PIR for initial PI-based HAART. In combination with two NRTIs, SQV/r has been effective as part of initial ARV therapy in several clinical trials in which it has performed as well as IDV/r but not consistently as well as LPV/r (Dragsted et al. 2003; Kirk et al. 1999; Lamotte et al. 2004; Roge et al. 2004) (Ananworanich et al. 2006; Dragsted et al. 2005; Raffi et al. 2007).

SQV/r should not ordinarily be used for salvage therapy because it has a low genetic barrier to resistance and because it has 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; Dragsted et al. 2005; Gathe et al. 2006; Haubrich et al. 2007; Katlama et al. 2007; Zolopa et al. 1999). Several genotypic resistance patterns that have been associated with high-level resistance to most PIs cause minimal SQV resistance. For example, L76V increases SQV susceptibility (Braun et al. 2007; Mueller et al. 2004; Rhee et al. 2006) and PI-resistant viruses with mutations at positions 32 and 47 or at positions 46 and 82 may remain susceptible to SQV. Susceptibility testing should be performed, however, before using SQV/r for salvage therapy when other options are available. Fold-reductions of 2-fold in the PhenoSense assay have been associated with reduced virologic response and fold reductions of 10 to 20-fold have been associate with complete loss of virologic response (Coakely et al. 2006).