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      AIDS prevention and control in the Yunnan region by T cell subset assessment

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          Abstract

          Background

          Prior to being spread throughout broader China, multiple human immunodeficiency virus (HIV)-1 genotypes were originally discovered in the Yunnan Province. As the HIV-1 epidemic continues its spread in Yunnan, knowledge of the influence of gender, age, and ethnicity to instances of HIV reservoirs will benefit monitoring the spread of HIV.

          Methods

          The degree to which T cells are depleted during an HIV infection depends on the levels of immune activation. T-cell subsets were assessed in newly-diagnosed HIV/AIDS patients in Yunnan, and the influence of age, gender, and ethnicity were investigated. Patients that were newly diagnosed with the HIV-infection between the years 2015 and 2018 at the First Affiliated Hospital of Kunming Medical College were selected for this study (N = 408). The lymphocyte levels and T cell subsets were retrospectively measured in whole blood samples by FACS analysis.

          Results

          The median CD4 count was 224 ± 191 cells/μl. Significantly higher mean frequencies and absolute numbers were observed in CD3 +, CD3 +CD4 +, CD3 +CD8 +, CD45 +, and CD3 +CD4 +/CD45 + in females compared to males. Han patients showed a higher total number of CD3+T cells and the ratio of CD3 + /CD45 + cells compared to any other ethnic minority (P < 0.001). The numbers of CD3+ T-cells, CD3+CD8+ T cells, and CD45+ T cells were highest in the age group ≥ 60. Significant differences were observed in the counts of CD3+, CD3+CD8+, and CD45 + cells and the ratio of CD3 +/CD45 + and CD3 +CD4 +/CD45 + cells between the ≤ 29 and 30–59 age groups.

          Conclusion

          This study has revealed that low levels of CD4 + T cells can be observed in newly-diagnosed HIV/AIDS patients in the Yunnan province. It has also been demonstrated that gender, age, and ethnicity have a significant association with the ratio of T-cell subsets that may contribute to virus progression and disease prognosis in individuals belonging to certain subsets of the population. This study has highlighted the importance of HIV/AIDS screening in at-risk populations to ensure timely and adequate clinical management in Yunnan.

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          Most cited references54

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          Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study.

          The critical role of chemokine receptors (CCR5 and CXCR4) in human immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a search for polymorphisms in other chemokine receptor genes that mediate HIV-1 disease progression. A mutation (CCR2-64I) within the first transmembrane region of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an allele frequency of 10 to 15 percent among Caucasians and African Americans. Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts (3003 patients) revealed that although CCR2-64I exerts no influence on the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2-64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele. Because CCR2-64I occurs invariably on a CCR5-+-bearing chromosomal haplotype, the independent effects of CCR5-Delta32 (which also delays AIDS onset) and CCR2-64I were determined. An estimated 38 to 45 percent of AIDS patients whose disease progresses rapidly (less than 3 years until onset of AIDS symptoms after HIV-1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+ genotype, whereas the survival of 28 to 29 percent of long-term survivors, who avoid AIDS for 16 years or more, can be explained by a mutant genotype for CCR2 or CCR5.
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            Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC)

            Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.
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              The unique HCV genotype distribution and the discovery of a novel subtype 6u among IDUs co-infected with HIV-1 in Yunnan, China.

              The Yunnan province is the epicenter of HIV-1 epidemics in China and a center for drug trafficking to the other parts of the world. In six prefectures of this province, a total of 132 IDUs were recruited to determine the sero-prevalence of HCV and HIV-1 and the positive rates were 93.94% and 68.18%, respectively (P<0.001). Co-infection with HCV and HIV-1 was found among 89 IDUs, of whom several HCV fragments were amplified and sequenced. Sequences of the HCV 5'NCR-C and NS5B region were determined from 82 IDUs. Phylogenetic analyses showed consistent genotyping among 80 IDUs. Among them HCV genotypes 1a, 1b, 3a, 3b, 6a, 6n, and a tentatively assigned novel 6u subtype were found in 1 (1.25%), 16 (20%), 19 (23.75%), 24 (30%), 4 (5%), 9 (11.25%) and 7 (8.75%) individuals, respectively. In two IDUs, genotyping results were discordant, suggesting mixed HCV infections or recombination. The proportion of patients with HCV 1b tended to decrease from the north to south and from the east to west in this province. Genotype 3 and 6 strains were more frequent in the southern prefectures. The novel subtype 6u strains were only detected in Dehong which borders Myanmar. Our findings showed a unique pattern of HCV genotype distribution, which is similar to that in the southeastern Asian countries but distinct from that among the general population in China. Routes of drug trafficking and the resulting high prevalence of HIV-1 infection may have contributed to this pattern of HCV genotype distribution.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: Data curationRole: InvestigationRole: MethodologyRole: ResourcesRole: Validation
                Role: Data curationRole: Formal analysisRole: MethodologyRole: SoftwareRole: ValidationRole: Visualization
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                18 April 2019
                2019
                : 14
                : 4
                : e0214800
                Affiliations
                [1 ] Yunnan Key Laboratory of Laboratory Medicine, Kunming, Yunan, China
                [2 ] Yunnan Institute of Laboratory Diagnosis, Kunming, Yunan, China
                [3 ] Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunan, China
                [4 ] Department of Medical Records and Statistics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunan, China
                [5 ] Department of Standardized Training, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunan, China
                [6 ] Department of Infectious Diseases, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunan, China
                Fudan University, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-7347-386X
                Article
                PONE-D-18-24524
                10.1371/journal.pone.0214800
                6472762
                30998710
                56a7267e-2ddc-4176-a46b-dba964215fb8
                © 2019 Li et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 September 2018
                : 20 March 2019
                Page count
                Figures: 5, Tables: 3, Pages: 14
                Funding
                Funded by: yunnan provincial department of science and technology and kunming medical university
                Award ID: 2015FB040
                Award Recipient :
                This study was funded by the Applied Basic Research in Yunnan Province (joint project of Yunnan Provincial Department of Science and Technology and Kunming Medical University) (grant number: 2015FB040). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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