The reverse transcriptase codon 69 insertion is observed in nucleoside reverse transcriptase inhibitor-experienced HIV-1-infected individuals, including those without prior or concurrent zidovudine therapy.
OBJECTIVE
This study was undertaken to examine 6-bp insertions following codon 69 in the reverse transcriptase (RT) coding region of human immunodeficiency virus type 1 (HIV-1) mutations in terms of incidence, presence of additional RT mutations, phenotypic drug resistance, HIV-1 RNA levels, and antiretroviral treatment history.


METHODS
A retrospective study of 121 nucleoside reverse transcriptase inhibitor (NRTI)-experienced subjects infected with HIV-1 was performed. Methods included quantitation of HIV-1 RNA levels, genotypic analyses of the RT and protease coding regions, and determination of phenotypic drug resistance.


RESULTS
A 6-bp insertion following RT codon 69 was observed in viral isolates from 4 subjects. Two subjects had a history of zidovudine (ZDV)-based therapy, and two subjects had a history of stavudine (D4T)-based therapy without prior exposure to ZDV. The T69S mutation and the 6-bp insertion following RT codon 69 were the only RT mutations observed in the 2 subjects with a history of D4T-based therapy.


CONCLUSIONS
Six-basepair insertions occurred in virus from 4 of 121 (3%) NRTI-experienced subjects, including those without prior ZDV treatment, and was observed in the absence of the T215Y mutation. There was no apparent correlation between insertion incidence and HIV-1 viremia.
Ross
L
L
Glaxo Wellcome, Inc., Research Triangle Park, North Carolina 27709, USA. llr8156@glaxowellcome.com
Johnson
M
M
Graham
N
N
Shaefer
M
M
St Clair
M
M
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003062:Codon; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009705:Nucleosides / Q000494:pharmacology* / Q000627:therapeutic use; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015215:Zidovudine / Q000494:pharmacology* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D003062:Codon; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D016333:HIV Protease