BACKGROUND: Most published data on antiretroviral-drug resistance is generated from in vitro or in vivo studies of subtype B virus. However, this subtype is associated with <10% of HIV infections worldwide, and it is essential to explore subtype-specific determinants of drug resistance. One potential cause of the differences between subtypes is the synonymous codon usage at key resistance positions. METHODS: We investigated the nucleotide sequences at drug resistance-related sites, for all major Brazilian subtypes (B, C, and F1) of human immunodeficiency virus type 1 (HIV-1) group M. RESULTS: We identified a change at positions 151 and 210 of the reverse-transcriptase region in subtype F1, such that the emergence of these key nucleoside/nucleotide analogue resistance mutations required an extra nucleotide change in subtype F1, compared with subtypes B and C. The clinical significance of position 210 was confirmed within a large Brazilian database, in which we identified a lower prevalence of the L210W mutation in subtype F1 virus, compared with subtype B virus, in patients matched for thymidine-analogue experience. An inverse relationship between the L210W and K70R mutations was also observed. CONCLUSIONS: The findings of the present study illustrate an important mechanism by which a subtype may determine genetic routes to resistance, with implications for treatment strategies for populations infected with HIV-1 subtype F.
BACKGROUND: Most published data on antiretroviral-drug resistance is generated from in vitro or in vivo studies of subtype B virus. However, this subtype is associated with <10% of HIV infections worldwide, and it is essential to explore subtype-specific determinants of drug resistance. One potential cause of the differences between subtypes is the synonymous codon usage at key resistance positions. METHODS: We investigated the nucleotide sequences at drug resistance-related sites, for all major Brazilian subtypes (B, C, and F1) of human immunodeficiency virus type 1 (HIV-1) group M. RESULTS: We identified a change at positions 151 and 210 of the reverse-transcriptase region in subtype F1, such that the emergence of these key nucleoside/nucleotide analogue resistance mutations required an extra nucleotide change in subtype F1, compared with subtypes B and C. The clinical significance of position 210 was confirmed within a large Brazilian database, in which we identified a lower prevalence of the L210W mutation in subtype F1 virus, compared with subtype B virus, in patients matched for thymidine-analogue experience. An inverse relationship between the L210W and K70R mutations was also observed. CONCLUSIONS: The findings of the present study illustrate an important mechanism by which a subtype may determine genetic routes to resistance, with implications for treatment strategies for populations infected with HIV-1 subtype F.
Authors: A Waléria-Aleixo; A N Martins; M B Arruda; R M Brindeiro; R M Da-Silva; F F Nobre; D B Greco; A Tanuri Journal: Antimicrob Agents Chemother Date: 2008-10-06 Impact factor: 5.191
Authors: Arthur H Robbins; Roxana M Coman; Edith Bracho-Sanchez; Marty A Fernandez; C Taylor Gilliland; Mi Li; Mavis Agbandje-McKenna; Alexander Wlodawer; Ben M Dunn; Robert McKenna Journal: Acta Crystallogr D Biol Crystallogr Date: 2010-02-12
Authors: Philippa J Easterbrook; Mel Smith; Jane Mullen; Siobhan O'Shea; Ian Chrystie; Annemiek de Ruiter; Iain D Tatt; Anna Maria Geretti; Mark Zuckerman Journal: J Int AIDS Soc Date: 2010-02-03 Impact factor: 5.396
Authors: Ana T Dumans; Cláudia C Barreto; André F Santos; Mônica Arruda; Thatiana M Sousa; Elizabeth S Machado; Ester C Sabino; Rodrigo M Brindeiro; Amílcar Tanuri; Alberto J Duarte; Marcelo A Soares Journal: Infect Genet Evol Date: 2008-10-17 Impact factor: 3.342