Abstract
HIV-1 Gag amino acid substitutions associated with protease inhibitor (PI) treatment have mainly been reported in subtype B, while information on other subtypes is scarce. Using sequences from 11613 patients infected with different HIV-1 subtypes, we evaluated the prevalence of 93 Gag amino acid substitutions and their association with genotypic PI resistance. A significant association was found for 13 Gag substitutions, including A431V in both subtype B and CRF01_AE. K415R in subtype C and S451G in subtype B were newly identified. Most PI-associated Gag substitutions are located in the flexible C-terminal domain, revealing the key role this region plays in PI resistance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-014-0079-7) contains supplementary material, which is available to authorized users.
Highlights
HIV-1 Gag amino acid substitutions associated with protease inhibitor (PI) treatment have mainly been reported in subtype B, while information on other subtypes is scarce
HIV-1 can escape PI selective pressure by the selection of substitutions in the protease substrate Gag [1,4,5,6,7]. Such Gag substitutions arising during PI-based treatment have mostly been characterized in HIV-1 subtype B (Additional file 1: Table S1), while only a few studies have focused on non-B subtypes using small cohorts of patients (Table 1)
We first investigated the emergence of non-B Gag substitutions during PI-based treatment in a cohort of 1068 patients followed at the University Hospital of Leuven, for which virological outcome and treatment information were available [12]
Summary
HIV-1 Gag amino acid substitutions associated with protease inhibitor (PI) treatment have mainly been reported in subtype B, while information on other subtypes is scarce. Such Gag substitutions arising during PI-based treatment have mostly been characterized in HIV-1 subtype B (Additional file 1: Table S1), while only a few studies have focused on non-B subtypes using small cohorts of patients (Table 1). We identified novel Gag substitutions in HIV-1 non-B subtypes using longitudinal data from patients failing PI-based therapy.
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