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

COLOCCINI RS; DILERNIA D; GHIGLIONE Y; TURK G; LAUFER N; RUBIO A; SOCIAS ME; SUED O; CAHN P; MANGANO A; SALOMÓN H; PANDO MA

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2014 vol. 9

1932-6203

Background: Variants in HIV-coreceptor C-C chemokine receptor type 5 (CCR5) and Human leukocyte antigen (HLA) genesare the most important host genetic factors associated with HIV infection and disease progression. Our aim was to analyzethe association of these genetic factors in the presence of clinical symptoms during Primary HIV Infection (PHI) and diseaseprogression within the first year.Methods: Seventy subjects diagnosed during PHI were studied (55 symptomatic and 15 asymptomatic). Viral load (VL) andCD4 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 characterizationwas 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 significantlyassociated with presence of HLA-A*11, HLA-A*24, and absence of HLA-A*31 and HLA-B*57. Higher 6-month VL wassignificantly associated with presence of CCR5-HHE, HLA-A*24, HLA-B*53, and absence of HLA-A*31 and CCR5-CF1. Lowerbaseline CD4 T-cell count was significantly associated with presence of HLA-A*24/*33, HLA-B*53, CCR5-CF2 and absence ofHLA-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 withpresence 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 agreewith previous studies performed in other groups. However, some genetic factor associations are being described for the firsttime, highlighting the importance of genetic studies at a local level.