Effect of the Q207D mutation in HIV type 1 reverse transcriptase on zidovudine susceptibility and replicative fitness

Although present as polymorphisms in HIV-1 sequences from untreated patients, mutations at reverse transcriptase (RT) codon 207 are found at higher frequency in samples from zidovudine-treated patients. Introduction of the Q207D mutation into the RT of a zidovudine (ZDV)-resistant isolate by site-directed mutagenesis increased ZDV resistance 2.7-fold but had no effect on ZDV susceptibility when introduced into wild-type RT. Zidovudine-resistant recombinant HIV-1 with and without 207D showed comparable fitness in growth competition assays in the absence of ZDV, but this mutation enhanced the fitness of ZDV-resistant recombinants in the presence of drug. These results suggest that when present with other thymidine analogue resistance mutations, 207D serves as a resistance mutation that improves the fitness of ZDV-resistant HIV-1. Analyzing viral fitness can provide important insights into the role of polymorphisms in drug resistance.