Analysis of enfuvirtide resistance mutations prevalence among HIV‐1 variants circulating in Russia and CIS countries

Abstract

BackgroundEnfuvirtide (ENF/Fuzeon/T‐20) was the first member of the class ‘fusion inhibitors’. This was approved for the treatment of HIV infection in the year 2003 in Europe and the USA. Fuzeon has not yet approved in Russia but in the near future his introduction expected. Resistance to ENF has been associated with mutations in the HR1 domain at codons 36–45. Mutations outside of this region and in the HR2 domain may also serve as secondary mutations. Unique and highly homogeneous HIV‐1 subtype A variant‐IDU‐A is the most prevailing in Russia and CIS countries. HIV‐1 genetic variants circulating in Russia and CIS countries and, in particular, variant IDU‐A are poorly studied on resistance mutations to enfuvirtide. The aim of this work was to study the prevalence of mutations associated to HIV fusion inhibitor enfuvirtide resistance in Russia and CIS countries.MethodsWe used 40 proviral DNA samples (12 IDU‐A sequences, 8 subtype B sequences, 6 subtype G sequences, 8 CRF03_AB recombinant sequences and 6 CRF02_AG recombinant sequences) isolated from peripheral blood mononuclear cells of HIV‐infected patients. All the samples belonged to enfuvirtide‐naïve patients. Fragments of env gene with coordinates 7754–8342 (corresponding to strain HXB2) were sequenced. Phylogenetic analysis was carried out using DNASTAR program package.ResultsEnfuvirtide resistance mutations were not found among viruses studied in Russia and CIS countries. The frequencies of natural polymorphism mutations associated with enfuvirtide hypersusceptibility were found to consist up to 35%, and the frequencies of accessory mutations N126K and E137K in the HR2 region‐up to 27.5%.ConclusionsEnfuvirtide resistance mutations are rare in Russia and CIS countries. HIV‐1 genetic variants circulating in Russia and CIS countries should be sensitive to enfuvirtide. However, accessory mutations in HR2 the case of HR1 resistance mutations may contribute to resistance development by improving viral fitness.