CORRELATION BETWEEN HIV SEQUENCE EVOLUTION, SPECIFIC IMMUNE-RESPONSE AND CLINICAL OUTCOME IN VERTICALLY INFECTED INFANTS

Objective: To evaluate sequence evolution in relation to different rat es of disease progression in infants infected with HIV-1. Design: Vari ability in the gp120 V3 region was analysed in HIV-1-infected children with different clinical courses, slow progression (n = 2) versus prog ressive disease (n = 3). Methods: Cloning and sequencing of virus-deri ved DNA from uncultured peripheral blood mononuclear cells was perform ed at two to three timepoints from birth and up to the fifth year of l ife. Sequence variability was estimated by calculating the genetic dis tance and the proportion and ratio of synonymous and non-synonymous nu cleotide substitutions over time. Results: Genetic distances were sign ificantly shorter in children with fast progression to disease, a pred ominance of synonymous nucleotide substitutions also being detected at later timepoints. Conversely, a preferential accumulation of nonsynon ymous nucleotide substitutions was apparent in children with slow dise ase progression. Furthermore, a positive correlation between a decreas ed ratio of synonymous/non-synonymous nucleotide substitutions and the ability of children's sera to react with synthetic peptides represent ing the autologous virus sequence was determined. Conclusion: Data sug gest that an antigenically more diverse virus population emerges in in fected children with slower progression to disease as a result of a st ronger immune pressure.