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

In vitro TPV has selected for the following major PI-resistance mutations: V32I, I54V, V82L, and I84V (Doyon et al. 2005). I47V, and I54A/M have been associated with reduced TPV susceptibility (Baxter et al. 2006; Parkin and Chappey 2006; Scherer et al. 2007).

V82L, V82T, and I84V have been the most common major PI-resistance mutations to emerge during TPV/r salvage therapy (Naeger and Struble 2007). V82L occurs in viruses that were wildtype at baseline; whereas V82T occurs in viruses with V82A at baseline (Baxter et al. 2006).

L90M was once considered a primary TPV-resistance mutation. However, in subsequent analyses it has shown to have little effect on TPV susceptibility (Piliero et al. 2006; Scherer et al. 2007).

L33F/I are among the most commonly occurring mutations to emerge during TPV/r treatment and are associated with decreased virologic response when combined with other major mutations.

E35G, K43T, Q58E, T74P, N83D, and L89V are nonpolymorphic mutations that have been associated with decreased virologic response to TPV/r in multivariate analyses (Baxter et al. 2006; Naeger and Struble 2007; Scherer et al. 2007).

L10V, I13V, K20MRV, M36I, and H69K are polymorphic mutations that were associated with decreased virological response to therapy in the RESIST studies. I13V, K20R, M36I, and H69K each represent the consensus amino acid in one or more non-B subtypes (Parkin and Schapiro 2004; Rhee et al. 2006).

TPV score: I50V is associated with increased TPV susceptibility (Elston et al. 2006; Scherer et al. 2007).

TPV/r is not recommended for initial HAART because it is associated with increased toxicity relative to other first line PIs against wildtype viruses (Cooper et al. 2006; Temesgen and Feinberg 2007).

In the RESIST studies, TPV/r outperformed APV/r, IDV/r, LPV/r, and SQV/r in treating persons with multiple past PI failures (Cahn et al. 2006; Gathe et al. 2006; Hicks et al. 2006). However, the difference between LPV/r and TPV/r did not reach statistical significance among LPV/r-naïve persons. Although it has not been compared directly to DRV/r, one analysis suggests that DRV/r is superior (Hill and Moyle 2007).

Several mutations have been associated with increased susceptibility to TPV relative to other PIs (e.g. G48V, V82A, I50V). However, because the genotypic correlates of reduced TPV susceptibility and reduced virologic response to TPV/r-containing salvage therapy regimens are complicated, phenotypic testing should be done to confirm the superior activity of TPV relative to that of other PIs before TPV/r is used for salvage therapy.