[Protease and reverse transcriptase genetic polymorphism in HIV type 1 subtype A variants predominating in cis...

Area of Science:

• Virology
• Molecular Biology
• Epidemiology

Background:

• Understanding HIV-1 drug resistance mutation frequencies is crucial for effective treatment strategies.
• Subtype A HIV-1 is prevalent in Russia, necessitating regional surveillance of genetic variations.
• Antiretroviral-naive individuals provide a baseline for assessing primary drug resistance.

Purpose of the Study:

• To determine the prevalence of drug resistance mutations in subtype A HIV-1 strains in Russia.
• To investigate the frequency of specific secondary mutations in protease and reverse transcriptase.
• To explore the evolutionary relationships and potential impact of gene pol polymorphism on HIV-1 fitness and drug resistance.

Main Methods:

• Analysis of nucleotide sequences encoding protease and reverse transcriptase from 141 antiretroviral-naive individuals.
• Genotyping of HIV-1 pol gene using HIV Biochip Hybridization microarray and Restriction fragment-length polymorphism (RFLP) in 178 additional isolates.
• Comparative analysis of HIV-1 variants based on the presence or absence of specific mutations (V77I, A62V).

Main Results:

• Low frequencies (<1%) of primary drug resistance mutations were observed.
• High frequencies of secondary mutations V77I (protease) and A62V (reverse transcriptase) were detected (67% and 63%, respectively).
• The combined MutV77I/A62V variant was predominant (56%) in Russia, geographically widespread, and prevalent in high-incidence regions.

Conclusions:

• A specific HIV-1 variant (MutV77I/A62V) with linked secondary mutations is dominant in Russia.
• These findings suggest a common origin for the predominant HIV-1 strains in the region.
• Further research is needed to understand the impact of these mutations on HIV-1 replicative fitness and drug resistance development.