Human immunodeficiency virus type 1 subtype F reverse transcriptase sequence and drug susceptibility

Area of Science:

• Virology
• Genetics
• Molecular Biology

Background:

• Human Immunodeficiency Virus type 1 (HIV-1) exhibits significant genetic diversity, with various subtypes impacting disease progression and treatment.
• Previous classification of Romanian HIV-1 isolates relied on env gene structure, necessitating confirmation through other genetic regions.

Purpose of the Study:

• To phylogenetically analyze the reverse transcriptase (RT) regions of the pol genes from 14 Romanian HIV-1 isolates.
• To confirm the classification of these isolates as HIV-1 subtype F based on pol gene sequences.
• To investigate the phenotypic susceptibility of subtype F to antiretroviral compounds.

Main Methods:

• Sequencing of the RT regions of the pol genes from 14 HIV-1 isolates.
• Phylogenetic analysis using neighbor-joining and maximum-likelihood methods.
• Phenotypic susceptibility testing against antiretroviral compounds, including TIBO derivative R82913.

Main Results:

• The Romanian HIV-1 strains clustered phylogenetically as subtype F based on pol gene analysis, correlating with env gene classification.
• Subtype F RT sequences showed significant divergence from Group M sequences (10.94% nucleotide, 7.6% amino acid).
• One strain exhibited natural resistance to R82913, indicating potential variability in drug susceptibility within subtype F.

Conclusions:

• This study provides the first report of HIV-1 subtype F pol sequences, confirming its distinct phylogenetic position.
• The findings highlight a strong correlation between env and pol gene phylogenetic analyses for HIV-1 classification.
• Virus genetic variability, as seen in subtype F, may influence antiretroviral treatment efficacy, underscoring the need for global evaluation of drug susceptibility across HIV-1 subtypes.