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

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.

• Authors: Sagar A Vaidya, Hendrik Streeck, Noor Beckwith, Musie Ghebremichael, Florencia Pereyra, Douglas S Kwon, Marylyn M Addo, Jenna Rychert, Jean-Pierre Routy, Heiko Jessen, Anthony D Kelleher, Frederick Hecht, Rafick-Pierre Sekaly, Mary Carrington, Bruce D Walker, Todd M Allen, Eric S Rosenberg, Marcus Altfeld
• Journal: Retrovirology (Retrovirology) Vol. 10 Pg. 139 (Nov 18 2013) ISSN: 1742-4690 [Electronic] England
• PMID: 24245727 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• HLA-B Antigens
• HLA-B57 antigen

Topics

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