Associations Between Phylogenetic Clustering and HLA Profile Among HIV-Infected Individuals in San Diego, California

Abstract

Specific sequence changes of human immunodeficiency virus type 1 (HIV-1) in the presence of specific HLA molecules may alter the composition and processing of viral peptides, leading to immune escape. Persistence of these mutations after transmission may leave the genetic fingerprint of the transmitter's HLA profile. Here, we evaluated the associations between HLA profiles and the phylogenetic relationships of HIV sequences sampled from a cohort of recently infected individuals in San Diego, California. We identified transmission clusters within the study cohort, using phylogenetic analysis of sampled HIV pol genotypes at a genetic distance of <1.5%. We then evaluated the association of specific HLA alleles, HLA homozygosity, HLA concordance, race and ethnicity, and mutational patterns within the clustering and nonclustering groups. From 350 cohort participants, we identified 162 clustering individuals and 188 nonclustering individuals. We identified trends for enrichment of particular alleles within individual clusters and evidence of viral escape within those clusters. We also found that discordance of HLA alleles was significantly associated with clustering individuals. Some transmission clusters demonstrate HLA enrichment, and viruses in these HLA-associated clusters often show evidence of escape to enriched alleles. Interestingly, HLA discordance was associated with clustering in our predominantly MSM population.