| BackgroundSexual transmission is the major route of HIV-1 infection in the world. About 70% to80% of HIV-1-infected cases occured through sexual transmission. HIV-1 is a highvariability retrovirus, which infection and disease progression process still need to beclarified. In AIDS molecular epidemiology studies, two kinds of populations are worthpaying attention to, one of which is HIV-exposed seronegative individuals (ESNs or ES) orhighly HIV-1-exposed and persistently seronegative (HEPS) individuals, the other infectedHIV-1 with long-term no-progressors (LTNP). At present, the mechanism of HIV-1non-susceptivity and its influential factors in HEPS individuals are still unclear, and thereare few reports on it in the world. Therefore, we select the HEPS individuals of HanChinese as the subjects and explore influential factors of HIV-1 non-susceptivity by sexualtransmission in our study.Objective1. To determine the genetic polymorphisms of CCR5-A32, CCR2b-64I and SDF1-3'Ain highly HIV-1-exposed and persistently seronegative (HEPS) individuals, and analyzetheir correlations with HIV-1 non-susceptibility.2. To detect the distribution of lymphocyte subsets in highly HIV-l-exposed andpersistently seronegative (HEPS) individuals, and analyze their correlations with HIV-1non-susceptibility.3. To detect the distribution and immune activation status of T lymphocyte subsets inhighly HIV-1-exposed and persistently seronegative (HEPS) individuals, and explore the immunologic mechanism of HIV-1 non-susceptibility by sexual transmission in HEPSindividuals.MethodsCase-control study was desiged in this study. Highly HIV-1-exposed persistentlyseronegative individuals by sexual transmission were enrolled as the cases, andHIV-1-seropositive individuals and healthy HIV-unexposed individuals were choosen as thecontrols. All subjects were voluntary counseling and test (VCT) individuals enrolled inShenzhen Center for Disease Control and Prevention from January 1, 2006 to December 31,2007. The cases and controls were matched by gender, ethnic, and age (within 5 years). Allof them were interviewed using the same questionnaire, whose blood samples were drawnin terms of the same conditions and standards. Polymerase chain reaction (PCR) andrestriction fragment length polymorphism (PCR/RFLP) analysis were used for genotypedetermination. Flow cytometry was used to analyze lymphocyte subsets and the expressionof activation markers.Results1. The CCR5-A32 mutation was not detected in HEPS, healthy HIV-unexposedindividuals and HIV-1-seropositive individuals (n=260). The allelic frequencies ofCCR2b-64I were 21.57%, 22.12%, 22.12% in the three groups respectively. There was notsignificant difference among the three groups on CCR2b-64I distribution. The allelicfrequencies of SDF1-3'A were 20.19%, 28.37% and 29.33% in the three groupsrespectively. There was significant difference in the allelic distribution of SDF1-3'Abetween HEPS and healthy HIV-unexposed individuals (P=0.023), also between HEPS andHIV-1-seropositive individuals (P=0.049).2. The differences in distributions of lymphocyte subsets were not significant betweenHEPS individuals and healthy HIV-unexposed individuals. CD4~+ counts, CD4/CD8 ratiowere higher in HEPS individuals and healthy HIV-unexposed individuals than those inHIV-1-seropositive individuals (P＜0.001), but CD8~+ counts were significantly lower in thetwo groups than that in HIV-1-seropositive individuals (P＜0.001); CD19~+ counts on B lymphocytes and CD16~+ CD56~+ counts on NK cells in HIV-1-seropositive individuals weresignificantly lower than those in I-IEPS individuals and healthy HIV-unexposed individuals.Correlation analysis showed that there were significantly positive correlations betweenCD19~+ counts on B lymphocytes, CD16~+ CD56~+ counts on NK cells and CD4~+ counts,CD8~+ counts in HIV-1-seropositive individuals and healthy HIV-unexposed individuals tosome extent. There were significantly positive correlations between CD19~+ counts on Blymphocytes and CD4~+ counts, CD8~+ counts, but significant correlations did not existbetween CD16~+ CD56~+ counts on NK cells and CD4~+ counts, CD8~+ counts in HEPSindividuals.3. Percentages of CD38~+/CD4~+, HLA-DR~+ CD38~+/CD4~+ were significantly lower inHEPS and healthy HIV-unexposed individuals than those in HIV-1-seropositive individuals(P＜0.001). Meanwhile, the percentage of HLA-DR~+ CD38~+/CD4~+ in HEPS individuals waslower than that in healthy HIV-unexposed individuals (P＜0.05). The percentage ofHLA-DR~+/CD4~+ in HEPS individuals was significantly lower than that inHIV-1-seropositive individuals and healthy HIV-unexposed individuals (P＜0.001).Conclusions1. The mutant genotypes on CCR5-A32 and CCR2b-64I were not correlated withHIV-1 infection through sexual transmission in Han Chinese. SDF1-3'A was associatedwith high risk of HIV-1 infection by sexual transmission in Han Chinese.2. There are no differences in distributions of lymphocyte subsets between HEPSindividuals and healthy HIV-unexposed individuals; CD4~+ counts on T lymphocytes,CD19~+ counts on B lymphocytes and CD16~+ CD56~+ counts on NK cells significantlydecrease for HIV-1-seropositive individuals.3. The expression of activation antigen marker HLA-DR on CD4~+ T cells was at a lowlevel, which probably was correlated with HIV-1 non-susceptibility in HEPS individuals bysexual transmission.
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