The prevalence and determinants of the K65R mutation in HIV-1 reverse transcriptase in tenofovir-naive patients.
The K65R mutation in HIV-1 reverse transcriptase is associated with reduced susceptibility to abacavir and tenofovir. We established its prevalence within a large clinical database, and investigated correlations with other resistance-associated mutations and antiretroviral history. The presence of K65R is associated with previous abacavir use. Although rare, it is preferentially selected within non-thymidine analogue-containing regimens, compared with concurrent zidovudine or stavudine use, which is associated with thymidine analogue mutations. Both genetic routes may compromise abacavir and tenofovir activity.
Winston
Alan
A
Department of Genitourinary/HIV Medicine, Chelsea and Westminster Hospital, London, UK.
Mandalia
Sundhiya
S
Pillay
Deenan
D
Gazzard
Brian
B
Pozniak
Anton
A
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016208:Databases, Factual; D015224:Dideoxynucleosides / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D009154:Mutation; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D015995:Prevalence; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000068698:Tenofovir; D000099227:Abacavir
D000225:Adenine; D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D054303:HIV Reverse Transcriptase; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000099227:Abacavir