Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam

Abstract

Background: Gag protein of human immunodeficiency virus (HIV) has been reported to play a crucial role in establishing infection, viral replication, and disease progression; thus, gag might be related to treatment response. The objective of this study was to investigate molecular genotypes of the gag gene, particularly the important functional binding domains in relation to treatment outcomes. Methods: HIV-infected children enrolled and treated at Vietnam National Children’s Hospital were recruited in the study. A total of 25 gag sequences were generated and used to construct phylogenetic trees and aligned with a reference sequence comparing 17 functional domains. Results: We found that all patients in a treatment failure (TF) group belonged to one cluster of the phylogenetic tree. In addition, the rate of mutations was significantly higher in TF compared with a treatment success (TS) group, specifically the PIP2 recognition motif, and the nucleocapsid basic and zinc motif 2 domains [median and (interquartile range (IQR): 12.5 (6.25–12.5) versus 50 (25–50), p < 0.01; 0 (0–0) versus 0 (0–21.43), p = 0.03 and 0 (0–7.14) versus 7.14 (7.14–7.14), p = 0.04, respectively]. When analyzing gag sequences at different time points in seven patients, we did not observe a consistent mutation pattern related to treatment response. Conclusion: Gag mutations in certain domains might be associated with increased viral load; therefore, studying the molecular genotype of the gag gene might be beneficial in monitoring treatment response in HIV-infected children.