Genetic Characterization of HIV-1 <i>tat</i> Gene from Virologically Controlled Aging Individuals with HIV on Long-Term Antiretroviral Therapy

Despite advancements in antiretroviral therapy (ART) that reduces the viral load to undetectable levels and improve CD4 T cell counts, viral eradication has not been achieved due to HIV-1 persistence in resting CD4⁺ T-cells. We, therefore, characterized the <i>tat</i> gene, which is essential for HIV-1 replication and pathogenesis, from 20 virologically controlled aging individuals with HIV (HIV⁺) on long-term ART and improved CD4⁺ T-cell counts, with a particular focus on older individuals. Peripheral blood mononuclear cell genomic DNA from HIV⁺ were used to amplify <i>tat</i> gene by polymerase chain reaction followed by nucleotide sequencing and analysis. Phylogenetic analysis showed that each HIV⁺ <i>tat</i> sequences were confined to their own subtrees and well discriminated from other HIV⁺ sequences. Moreover, there was a low degree of viral heterogeneity and lower estimates of genetic diversity within these individuals' <i>tat</i> sequences, which decreased with increasing CD4 T counts in these HIV⁺. Most HIV⁺ Tat deduced amino acid sequences showed intact open reading frames and maintained the important functional domains for Tat functions, including transactivation, TAR binding, and nuclear localization. Furthermore, Tat-deduced amino acid sequences showed variation in previously characterized cytotoxic T lymphocytes (CTL) epitopes, suggesting escape mutants. In conclusion, a low degree of genetic variability and conservation of functional domains and variations in CTL epitopes were the features of <i>tat</i> sequences that may be contributing to viral persistence in these 20 aging individuals with HIV on long-term ART.