Substitutions in the Reverse Transcriptase and Protease Genes of HIV-1 Subtype B in Untreated Individuals and Patients Treated With Antiretroviral Drugs.

ABSTRACT : 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.