title: Association of HIV diversity and survival in HIV-infected Ugandan infants.
abstract: BACKGROUND
  The level of viral diversity in an HIV-infected individual can change during the course of HIV infection, reflecting mutagenesis during viral replication and selection of viral variants by immune and other selective pressures. Differences in the level of viral diversity in HIV-infected infants may reflect differences in viral dynamics, immune responses, or other factors that may also influence HIV disease progression. We used a novel high resolution melting (HRM) assay to measure HIV diversity in Ugandan infants and examined the relationship between diversity and survival through 5 years of age.
  
  
  METHODS
  Plasma samples were obtained from 31 HIV-infected infants (HIVNET 012 trial). The HRM assay was used to measure diversity in two regions in the gag gene (Gag1 and Gag2) and one region in the pol gene (Pol).
  
  
  RESULTS
  HRM scores in all three regions increased with age from 6-8 weeks to 12-18 months (for Gag1: P = 0.005; for Gag2: P = 0.006; for Pol: P = 0.016). Higher HRM scores at 6-8 weeks of age (scores above the 75(th) percentile) were associated with an increased risk of death by 5 years of age (for Pol: P = 0.005; for Gag1/Gag2 (mean of two scores): P = 0.003; for Gag1/Gag2/Pol (mean of three scores): P = 0.002). We did not find an association between HRM scores and other clinical and laboratory variables.
  
  
  CONCLUSIONS
  Genetic diversity in HIV gag and pol measured using the HRM assay was typically low near birth and increased over time. Higher HIV diversity in these regions at 6-8 weeks of age was associated with a significantly increased risk of death by 5 years of age.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Maria M
authors.initials: MM
authors.lastname: James
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Philippa
authors.initials: P
authors.lastname: Musoke
authors.forename: Deborah
authors.initials: D
authors.lastname: Donnell
authors.forename: Jessica
authors.initials: J
authors.lastname: Fogel
authors.forename: William I
authors.initials: WI
authors.lastname: Towler
authors.forename: Leila
authors.initials: L
authors.lastname: Khaki
authors.forename: Clemensia
authors.initials: C
authors.lastname: Nakabiito
authors.forename: J Brooks
authors.initials: JB
authors.lastname: Jackson
authors.forename: Susan H
authors.initials: SH
authors.lastname: Eshleman
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D006678:HIV / Q000145:classification*; D015658:HIV Infections / Q000821:virology*; D006801:Humans; D007223:Infant; D016019:Survival Analysis; D014454:Uganda; D019562:Viral Load
chemical_list: D017931:DNA Primers