Temporal effect of HLA-B*57 on viral control during primary HIV-1 infection

Retrovirology. 2013 Nov 18:10:139. doi: 10.1186/1742-4690-10-139.

Abstract

Background: HLA-B alleles are associated with viral control in chronic HIV-1 infection, however, their role in primary HIV-1 disease is unclear. This study sought to determine the role of HLA-B alleles in viral control during the acute phase of HIV-1 infection and establishment of the early viral load set point (VLSP).

Findings: Individuals identified during primary HIV-1 infection were HLA class I typed and followed longitudinally. Associations between HLA-B alleles and HIV-1 viral replication during acute infection and VLSP were analyzed in untreated subjects. The results showed that neither HLA-B*57 nor HLA-B*27 were significantly associated with viral control during acute HIV-1 infection (Fiebig stage I-IV, n=171). HLA-B*57 was however significantly associated with a subsequent lower VLSP (p<0.001, n=135) with nearly 1 log10 less median viral load. Analysis of a known polymorphism at position 97 of HLA-B showed significant associations with both lower initial viral load (p<0.01) and lower VLSP (p<0.05). However, this association was dependent on different amino acids at this position for each endpoint.

Conclusions: The effect of HLA-B*57 on viral control is more pronounced during the later stages of primary HIV-1 infection, which suggests the underlying mechanism of control occurs at a critical period in the first several months after HIV-1 acquisition. The risk profile of polymorphisms at position 97 of HLA-B are more broadly associated with HIV-1 viral load during primary infection and may serve as a focal point in further studies of HLA-B function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Amino Acid Substitution
  • Female
  • HIV Infections / immunology*
  • HIV Infections / virology*
  • HIV-1 / immunology*
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Point Mutation
  • Polymorphism, Genetic
  • Time Factors
  • Viral Load

Substances

  • HLA-B Antigens
  • HLA-B57 antigen