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

R.S. COLOCCINI; Y. GHIGLIONE; G. TURK; N. LAUFER; M.E. SOCÍAS; O. SUED; P. CAHN; H. SALOMÓN; A. MANGANO; M.A. PANDO

Kuala Lumpur

Congreso; 7TH IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2013

International AIDS Society

Background: Variants in HIV-coreceptor C C R5 and 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 post-infection. Methods: Seventy patients diagnosed during acute/early PHI were studied (55 symptomatic and 15 asymptomatic). HIV progression was defined by presence of B or C events and/or C D4 T-cell count < 350cell/mm3 . Haplotypes of C C R5 (A-E, F1/F2 and G1/G2) were characterized by PC R and SDMPC R-RFLP. C C L3L1 C opy Number (C N) was determined by Taqman real-time PC R. HLA-I characterization was performed by Sequencing-Based Typing. Plasma LPS was quantified by LAL-assay. HIV tropism was determined by gp120 V3 loop sequencing. Viral load(VL) (bDNA) and C D4T-cell count (flow cytometry) were evaluated. The Fisher's exact or Mann-Whitney tests were used to determine association between variables, a p value < 0.05 was considered statistically significant. Results: Symptomatic-PHI patients had higher baseline VL(p=0.004) and plasma LPS(p=0.038). Symptoms during PHI were significantly associated with lower frequency of C C R5-C F1, HLA-B*39 and HLA-B*50. Moreover, lower frequency of C C R5-HHC (52.7%vs.73.3%), low C C L3L1-C N(2.4vs.3.1) and higher frequency of C C R5-HHE (65.5%vs.40%) and X4 tropic HIV variants (26.1%vs.16.7%) were found. Progression was significantly associated with higher frequency of C C R5-C F2 and HLA-A*11. Higher baseline VL was significantly associated with presence of HLA-A*24, HLA-A*11 and absence of HLAA*31, HLA-A*36, HLA-B*37, HLA-B*42 and HLA-B*57. Furthermore, higher six-month VL was significantly associated with presence of HLA-A*24, HLAB*53, C C R5-HHE and absence of HLA-A*31 and C C R5-C F1. Lower baseline C D4 T-cell count was significantly associated with presence of HLA-A*24, HLAA*33, C C R5-C F2 and absence of HLA-A*23, HLA-A*01 and C C R5-HHA. Moreover, lower 12-month C D4 T-cell count was significantly associated with presence of HLA-A*33, HLA-B*14, HLA-C *08, C C R5-C F2 and absence of HLA-B*07, HLA-C *07 and HLA-C *14. Conclusion: Significant associations of host factors with early disease progression were found in a cohort of Argentinean acute/early infected patients. As our knowledge, association of lower C C R5-C F1 with presence of symptoms and higher VL has not been described previously. These results highlight the importance of genetic background in virus control.