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.

Objectives: 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.

Study design/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.