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

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

Kuala Lumpur

Conferencia; 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013); 2013

IAS

Background Variants in HIV-coreceptor CCR5 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 CD4 T-cell count <350cell/mm3. Haplotypes of CCR5 (A-E, F1/F2 and G1/G2) were characterized by PCR and SDM-PCR-RFLP. CCL3L1 Copy Number (CN) was determined by Taqman real-time PCR. 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 CD4 T-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 CCR5-CF1, HLA-B*39 and HLA-B*50. Moreover, lower frequency of CCR5-HHC (52.7%vs.73.3%), low CCL3L1-CN(2.4vs.3.1) and higher frequency of CCR5-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 CCR5-CF2 and HLA-A*11. Higher baseline VL was significantly associated with presence of HLA-A*24, HLA-A*11 and absence of HLA-A*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, HLA-B*53, CCR5-HHE and absence of HLA-A*31 and CCR5-CF1. Lower baseline CD4 T-cell count was significantly associated with presence of HLA-A*24, HLA-A*33, CCR5-CF2 and absence of HLA-A*23, HLA-A*01 and CCR5-HHA. 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, 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 CCR5-CF1 with presence of symptoms and higher VL has not been described previously. These results highlight the importance of genetic background in virus control.