Evidence of genomic information and structural restrictions of HIV-1 PR and RT gene regions from individuals experiencing antiretroviral virologic failure.

OBJECTIVES

This study analyzed Protease-PR and Reverse Transcriptase-RT HIV-1 genomic information entropy metrics among patients under antiretroviral virologic failure, according to the numbers of virologic failures or resistance mutations.

METHODS

For this purpose, we used genomic sequences from PR and RT of HIV-1 from a cohort of chronic patients followed up at São Paulo Hospital.

RESULTS

Informational entropy proportionally increases with the number of antiretroviral virologic failures in PR and RT (p < .001). Affected regions of PR were related to catalytic and structural functions, such as Fulcrum (K20) Flap (M46) and Cantilever (A71). In RT, this occurred at Fingers (E44) and Palm (K219). Informational entropy increases according to the number of resistance mutations in PR and RT (p < .001). Higher PR entropy was proportional to the resistance mutation numbers in Fulcrum (L10), Active site (L24) Flap (M46), Cantilever (L63) and near Interface (L90). In RT, they related to regions responsible for protein stability such as Fingers (T39) and Palm (L100).

CONCLUSIONS

The antiretroviral selective pressure affects HIV genomic informational entropy at the PR and RT regions, leading to the emergence of more unstable virions. Mapping the three-dimensional structure in these HIV-1 proteins is relevant to designing new antiretroviral targeting resistant strains.