High prevalence of natural polymorphisms in Gag (CA-SP1) associated with reduced response to Bevirimat, an HIV-1 maturation inhibitor.
Mutations H358Y, L363F/M, A364V and A366T/V confer in-vitro resistance to bevirimat. Moreover, polymorphisms at the Glutamine-Valine-Threonine (QVT) motif (369-371) have been associated with reduced bevirimat activity in vivo. The rate of these changes was assessed in 389 HIV+ patients naïve for bevirimat. QVT polymorphisms were frequent (47%), especially in non-B subtypes (93%). Conversely, only four patients (1%) harbored major bevirimat resistance mutations. Finally, specific gag changes were associated with protease inhibitor resistance mutations in subtype B viruses.
Seclén
Eduardo
E
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
González
María Del Mar
Mdel M
Corral
Angélica
A
de Mendoza
Carmen
C
Soriano
Vincent
V
Poveda
Eva
E
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D015995:Prevalence; D013386:Succinates / Q000627:therapeutic use*; D014315:Triterpenes / Q000627:therapeutic use*; D053978:Pentacyclic Triterpenes
D019380:Anti-HIV Agents; D013386:Succinates; D014315:Triterpenes; C479935:bevirimat; D053978:Pentacyclic Triterpenes