Host genetic factors associated with symptomatic primary HIV infection and disease progression among Argentinean seroconverters

PLoS One. 2014 Nov 18;9(11):e113146. doi: 10.1371/journal.pone.0113146. eCollection 2014.

Abstract

Background: Variants in HIV-coreceptor C-C chemokine receptor type 5 (CCR5) and Human leukocyte antigen (HLA) genes are the most important host genetic factors associated with HIV infection and disease progression. Our aim was to analyze the association of these genetic factors in the presence of clinical symptoms during Primary HIV Infection (PHI) and disease progression within the first year.

Methods: Seventy subjects diagnosed during PHI were studied (55 symptomatic and 15 asymptomatic). Viral load (VL) and CD4 T-cell count were evaluated. HIV progression was defined by presence of B or C events and/or CD4 T-cell counts <350 cell/mm3. CCR5 haplotypes were characterized by polymerase chain reaction and SDM-PCR-RFLP. HLA-I characterization was performed by Sequencing.

Results: Symptoms during PHI were significantly associated with lower frequency of CCR5-CF1 (1.8% vs. 26.7%, p = 0.006). Rapid progression was significantly associated with higher frequency of CCR5-CF2 (16.7% vs. 0%, p = 0.024) and HLA-A*11 (16.7% vs. 1.2%, p = 0.003) and lower frequency of HLA-C*3 (2.8% vs. 17.5%, p = 0.035). Higher baseline VL was significantly associated with presence of HLA-A*11, HLA-A*24, and absence of HLA-A*31 and HLA-B*57. Higher 6-month VL was significantly associated with presence of CCR5-HHE, HLA-A*24, HLA-B*53, and absence of HLA-A*31 and CCR5-CF1. Lower baseline CD4 T-cell count was significantly associated with presence of HLA-A*24/*33, HLA-B*53, CCR5-CF2 and absence of HLA-A*01/*23 and CCR5-HHA. Lower 6-month CD4 T-cell count was associated with presence of HLA-A*24 and HLA-B*53, and absence of HLA-A*01 and HLA-B*07/*39. Moreover, lower 12-month CD4 T-cell count was significantly associated with presence of HLA-A*33, HLA-B*14, HLA-C*08, CCR5-CF2, and absence of HLA-B*07 and HLA-C*07.

Conclusion: Several host factors were significantly associated with disease progression in PHI subjects. Most results agree with previous studies performed in other groups. However, some genetic factor associations are being described for the first time, highlighting the importance of genetic studies at a local level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argentina
  • Blotting, Western
  • CD4 Lymphocyte Count
  • Disease Progression
  • HIV Seropositivity / genetics*
  • HLA Antigens / genetics*
  • Haplotypes / genetics
  • Host-Derived Cellular Factors / metabolism*
  • Humans
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Receptors, CCR5 / genetics*
  • Viral Load

Substances

  • CCR5 protein, human
  • HLA Antigens
  • Host-Derived Cellular Factors
  • Receptors, CCR5

Grants and funding

This research was funded by grants from: Agencia Nacional de Promoción Científica y Tecnológica (grant number 2008-0559), “Fundación Florencio Fiorini” (period: 2009–2010), UBACYT (period: 2010–2012) and CONICET (PIP 2011–2013). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.