The ability to provide effective long-term antiretroviral therapy using single agents for human immunodeficiency virus type 1 (HIV-1) infection became a complex issue when the isolation of HIV-1 strains that were less sensitive to 3'-azido-2',3'-dideoxythymidine (AZT or zidovudine) in vitro from patients with acquired immunodeficiency syndrome (AIDS) who received AZT therapy for more than 6 months was reported in 1989. Nucleotide sequence analysis of the reverse transcriptase-coding region from pairs of AZT-sensitive and -resistant HIV-1 isolates have revealed several mutations that result in amino acid substitutions in the viral reverse transcriptase. These amino acid substitutions include: (i) Asp at amino acid position-67 to Asn (designated Asp-67 -> Asn); (ii) Lys-70 -> Arg; (iii) Thr-215 -> Tyr or Thr-215 -> Phe; and (iv) Lys-219 -> Gln.
