Substitutions in the reverse transcriptase and protease genes of HIV-1 subtype B in untreated individuals and patients treated with antiretroviral drugs.

The nucleotide transition G-->A is known as a hypermutation due to its high prevalence in HIV-1 and other pathogens. However, the contribution of the G-->A transition in the generation of drug resistance mutations is unknown . Our objective was to ascertain the rate of nucleotide substitutions in protease (PR) and reverse transcriptase (RT) in both untreated and treated HIV-1 patients. Genotypic analysis was performed on viruses from both treated and untreated patients with subtype B infections. Nucleotide genomic diversity was compared with a consensus subtype B reference virus. Then, the prevalence of resistance-associated mutations in different subgroups of treated patients was evaluated in relation to the patterns of nucleotide transitions. In untreated patients (n = 50) G-->A was most prevalent, followed by A-->G, C-->T, and T-->C transitions. In treated patients (n = 51), the prevalence of A-->G was similar to that of G-->A. Among mutations that confer resistance to antiretroviral drugs, M184V was present in 76% of treated patients and K70R in 31% (A-->G transitions). Other frequent mutations in RT included T215Y (C-->A and A-->T substitutions), which was prevalent in 31% of treated patients. In PR, a L90M (T-->A substitution) was prevalent in 47% of protease inhibitor (PI)-treated patients. In conclusion, the G-->A transition was most prevalent in RT and PR among untreated patients. In contrast, A-->G was the most prevalent transition in patients treated with antiretroviral drugs.