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      Evolving Molecular Epidemiological Profile of Human Immunodeficiency Virus 1 in the Southwest Border of China

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          Abstract

          Background

          We have previously reported in Xishuangbanna (Banna) Dai Autonomous Prefecture, a well-developed tourist destination in the southwest border of China, that HIV-1 transmitted dominantly through heterosexual contact with less divergent genotypes and few drug resistant mutations [1]. Due to the rapid increase of newly diagnosed HIV-1 cases per year in Banna in recent years, it’s important to evaluate the evolution of HIV-1 molecular epidemiology for the better understanding of ongoing HIV-1 outbreak in this region.

          Methodology/Principal Findings

          By sequencing of HIV-1 pol genes and phylogenetic analysis, we conducted a molecular epidemiologic study in 352 HIV-1-seropositive highly active antiretroviral treatment (HAART)-naïve individuals newly diagnosed at the Banna Center for Disease Control and Prevention between 2009 and 2011. Of 283 samples (84.1% taken from heterosexually acquired adults, 10.6% from needle-sharing drug users, 2.8% from men who have sex with men, 0.4% from children born from HIV-1-infected mothers, and 2.1% remained unknown) with successful sequencing for pol gene, we identified 108 (38.2%) HIV-1 subtype CRF08_BC, 101 (35.7%) CRF01_AE, 49 (17.3%) CRF07_BC, 5 (1.8%) C/CRF57_BC, 3 (1.1%) B’, 1 (0.4%) B/CRF51_01B, and 16 (5.7%) unique recombinants forms. Among these infected individuals, 104 (36.7%) cases showed drug resistant or resistance-relevant mutations, and 4 of them conferring high-level resistance to 3TC/FTC, EFV/NVP or NFV. Phylogenetic analysis revealed 21 clusters (2–7 sequences) with only 21.2% (60/283) sequences involved.

          Conclusion/Significance

          In contrast to our previous findings, CRF08_BC, replaced CRF01_AE, became the dominant genotype of HIV-1 in Banna prefecture. The viral strains with drug resistance mutations were detected frequently in newly diagnosed HIV-1-infected individuals in this region.

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          Most cited references14

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          Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination.

          The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env, nef, and the 3' long terminal repeat as determined by both maximal chi2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher (P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.
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            HIV-1 pol gene variation is sufficient for reconstruction of transmissions in the era of antiretroviral therapy.

            We wished to assess the potential of using HIV-1 pol gene for the identification of transmissions events by phylogenetic means in the era of antiretroviral drug selective pressure. The relatedness of the viruses within a large database of pol sequences generated from HIV-1 infected individuals from the UK was reconstructed by phylogenetic analyses. A total of 140 pol sequences were selected out of the 2500 database entries, on the basis of a pairwise genetic distance higher than 95%. Neighbour Joining and Maximum Likelihood trees were implemented. Trees were reconstructed after exclusion of codon positions associated with drug resistance from the original pol alignment. Trees based on the corresponding env and gag genes were implemented to confirm the linkages. Up to 23 transmission clusters were identified, supported by high bootstrap values (> 99), congruent epidemiological data and/or similar drug resistance motifs. The topology of the tree was consistent after exclusion of the drug resistance associated codons. Identical topologies were obtained in trees implemented from gag and env genes alignments. Despite its genetic conservation, the HIV-1 pol gene holds sufficient variability to permit the phylogenetic reconstruction of transmissions. Identical clusters were obtained whichever of the three principal genes is considered and no bias was induced by the presence of drug resistance mutations. These findings demonstrate the important epidemiological information inherent within routinely collected laboratory data, which can assist in estimating rates of recent HIV-1 transmission within a population.
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              Sexual behavior and risks for HIV infection and transmission among male injecting drug users in Yunnan, China.

              To analyze the risk factors, particularly sexual behaviors, associated with HIV infection, and to describe the risks for HIV transmission among male injecting drug users (IDUs) in China. A cross-sectional study of 314 IDUs in Yunnan Province was conducted. Information on demographics, HIV serostatus, and sexual and drug-using behaviors was collected. HIV prevalence among the study subjects was 59.9%. HIV infection was associated with older age (> or = 27 years), early drug initiation (at or = once a day). Thirty-seven percent reported multiple sexual partners. Consistent condom use rates were lowest with regular partners (23.8%), followed by 42.5% with casual partners, and 57.3% with female sex workers. Ninety-eight percent of subjects received high 'HIV knowledge' scores. Few of the subjects who needed medical care sought it out. Despite awareness of HIV, needle sharing and unprotected sex persist in the population, and the HIV prevalence is high. Further interventions should not only seek to educate but also to reduce high-risk behaviors.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                10 September 2014
                : 9
                : 9
                : e107578
                Affiliations
                [1 ]Sino-French Collaborative Laboratory, Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou, China
                [2 ]Institut de Recherche sur les Vaccins et l’Immunologie des Cancers et du Sida, Université Paris Descartes/Institut de Recherche pour le Développement, Paris, France
                [3 ]Xishuangbanna Center for Disease Control and Prevention, Jinghong, Yunnan, People’s Republic of China
                University of Athens, Medical School, Greece
                Author notes

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

                Conceived and designed the experiments: YC SC JK HF HD WG CL ML JF LF JMA WL. Performed the experiments: YC SC JK HF HD WG CL ML. Analyzed the data: YC SC WL. Contributed reagents/materials/analysis tools: YC SC WL. Wrote the paper: YC SC WL

                Article
                PONE-D-14-02069
                10.1371/journal.pone.0107578
                4160289
                25207977
                05b837ea-a033-4f1a-bd9d-427b88a26306
                Copyright @ 2014

                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
                : 16 April 2014
                : 19 August 2014
                Page count
                Pages: 11
                Funding
                This work was supported by the Institut de Recherche pour le Développement (IRD) and the Institut de Recherche sur les Vaccins et l’Immunothérapie des Cancers et du Sida (IRVICS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Viral Pathogens
                Immunodeficiency Viruses
                HIV
                Medicine and health sciences
                Epidemiology
                HIV epidemiology
                Molecular epidemiology
                Infectious Diseases
                Viral Diseases

                Uncategorized
                Uncategorized

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