Abstract
BackgroundVariants 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.MethodsSeventy 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.ResultsSymptoms 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.ConclusionSeveral 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.
Highlights
Research studies on primary HIV infection (PHI) are increasing worldwide to better understand the natural history of HIV infection and to identify the most important disease prognostic markers
Based on the effects of host genetic variations described on HIV disease progression, our aim was to analyze the association of chemokine receptor type 5 (CCR5)/CCL3L1 system and Human leukocyte antigen (HLA) in the presence of clinical symptoms during Primary HIV Infection (PHI) and disease progression within the first year post-infection
Frequency of CCR5 haplotypes/genotypes and CCL3L1 Similar to the results found in Argentinean children exposed perinatally to HIV [42] and blood donors [43], the most frequent CCR5 haplotypes in the PHI group were HHE (36.4%) and HHC (30.7%)
Summary
Research studies on primary HIV infection (PHI) are increasing worldwide to better understand the natural history of HIV infection and to identify the most important disease prognostic markers. As most of these studies were performed in other countries and due to genetic differences in the circulating virus and in the host, local studies are needed to better understand the particular characteristics of HIV infection dynamics [1]. 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
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