Deep-sequencing of viral genomes from treatment-naive HIV-infected persons shows positive association between intrahost genetic diversity and viral load

Background: Infection with human immunodeficiency virus type 1 (HIV) typically results from transmission of a small and genetically uniform viral population. Following transmission, the virus population becomes more diverse because of recombination and acquired mutations through genetic drift and selection. Viral intrahost genetic diversity remains a major obstacle to the cure of HIV; however, there is a disagreement whether intrahost viral genetic diversification associates positively or negatively with disease progression and progression markers. Viral load is a key progression marker and understanding its relationship to viral intrahost genetic diversity could help design future strategies for HIV monitoring and treatment. Methods: We analyzed deep-sequenced viral genomes from 2,650 treatment-naive HIV-infected persons to measure the intrahost genetic diversity of 2,447 genomic codon positions as calculated by Shannon entropy. We tested for associations between viral load (VL) and am...