OBJECTIVES: To identify accessory mutations associated with high-level resistance to reverse transcriptase (RT) inhibitors in HIV-1 subtypes B and C. METHODS: Changes relative to the wild-type for codons 1-400 of RT were analysed from treatment-experienced patients infected with subtypes B (5464 patients) and C (1920 patients). Positions associated with the accumulation of mutations conferring resistance to thymidine analogues and to non-nucleoside RT inhibitors (NNRTIs) were identified. A subtype-specific single-replication cycle drug susceptibility assay was used to determine whether some of the mutations affected drug susceptibility or viral infectivity. RESULTS: In subtype B, mutations at 31 and 26 positions were associated with the accumulation of thymidine analogue mutations (TAMs) and NNRTI mutations, respectively; in subtype C, 18 and 13 positions were identified, respectively. Amino acid changes at the following positions were differentially associated with (i) the accumulation of 0-4+ TAMs in subtypes B and C (away from consensus): 43 (27.0% B versus 2.5% C); 118 (36.4% B versus 16.2% C); 135 (12.5% B versus 28.0% C); and 326 (2.6% towards consensus in B versus 7.6% away in C) and (ii) the accumulation of 0-3+ NNRTI mutations (away from consensus): 43 (10.2% B versus 0.5% C); and 68 (5.2% B versus 10.3% C). Codon changes K43E, E44D and V118I were found to have no effect on susceptibility to three NRTIs with or without TAMs in either subtype; however, some accessory mutations had subtype-specific effects on viral infectivity. CONCLUSIONS: Differences between subtypes B and C were observed in the development and effect of accessory mutations associated with high-level resistance to RT inhibitors.
OBJECTIVES: To identify accessory mutations associated with high-level resistance to reverse transcriptase (RT) inhibitors in HIV-1 subtypes B and C. METHODS: Changes relative to the wild-type for codons 1-400 of RT were analysed from treatment-experienced patients infected with subtypes B (5464 patients) and C (1920 patients). Positions associated with the accumulation of mutations conferring resistance to thymidine analogues and to non-nucleoside RT inhibitors (NNRTIs) were identified. A subtype-specific single-replication cycle drug susceptibility assay was used to determine whether some of the mutations affected drug susceptibility or viral infectivity. RESULTS: In subtype B, mutations at 31 and 26 positions were associated with the accumulation of thymidine analogue mutations (TAMs) and NNRTI mutations, respectively; in subtype C, 18 and 13 positions were identified, respectively. Amino acid changes at the following positions were differentially associated with (i) the accumulation of 0-4+ TAMs in subtypes B and C (away from consensus): 43 (27.0% B versus 2.5% C); 118 (36.4% B versus 16.2% C); 135 (12.5% B versus 28.0% C); and 326 (2.6% towards consensus in B versus 7.6% away in C) and (ii) the accumulation of 0-3+ NNRTI mutations (away from consensus): 43 (10.2% B versus 0.5% C); and 68 (5.2% B versus 10.3% C). Codon changes K43E, E44D and V118I were found to have no effect on susceptibility to three NRTIs with or without TAMs in either subtype; however, some accessory mutations had subtype-specific effects on viral infectivity. CONCLUSIONS: Differences between subtypes B and C were observed in the development and effect of accessory mutations associated with high-level resistance to RT inhibitors.
Authors: Natalie N Kinloch; Guinevere Q Lee; Jonathan M Carlson; Steven W Jin; Chanson J Brumme; Helen Byakwaga; Conrad Muzoora; Mwebesa B Bwana; Kyle D Cobarrubias; Peter W Hunt; Jeff N Martin; Mary Carrington; David R Bangsberg; P Richard Harrigan; Mark A Brockman; Zabrina L Brumme Journal: J Virol Date: 2018-12-10 Impact factor: 5.103
Authors: Suwellen Sardinha Dias de Azevedo; Edson Delatorre; Cibele Marina Gaido; Carlos Silva-de-Jesus; Monick Lindenmeyer Guimarães; José Carlos Couto-Fernandez; Mariza G Morgado Journal: Viruses Date: 2022-08-12 Impact factor: 5.818