Dataset Information

Prognosis of HIV Patients Receiving Antiretroviral Therapy According to CD4 Counts: A Long-term Follow-up study in Yunnan, China.

ABSTRACT: We aim to evaluate the overall survival and associated risk factors for HIV-infected Chinese patients on antiretroviral therapy (ART). 2517 patients receiving ART between 2006 and 2016 were prospectively enrolled in Yunnan province. Kaplan-Meier analyses and Cox proportional hazard regression analyses were performed. 216/2517 patients died during a median 17.5 (interquartile range [IQR] 6.8-33.2) months of follow-up. 82/216 occurred within 6 months of starting ART. Adjusted hazard ratios were10.69 (95%CI 2.38-48.02, p?=?0.002) for old age, 1.94 (95%CI 1.40-2.69, p?

SUBMITTER: Ren L

PROVIDER: S-EPMC5575268 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Prognosis of HIV Patients Receiving Antiretroviral Therapy According to CD4 Counts: A Long-term Follow-up study in Yunnan, China.

Ren Li L Li Juan J Zhou Shiyi S Xia Xueshan X Xie Zhenrong Z Liu Pan P Xu Yu Y Qian Yuan Y Zhang Huifeng H Ma Litang L Pan Qiuwei Q Wang Kunhua K

Scientific reports 20170829 1

We aim to evaluate the overall survival and associated risk factors for HIV-infected Chinese patients on antiretroviral therapy (ART). 2517 patients receiving ART between 2006 and 2016 were prospectively enrolled in Yunnan province. Kaplan-Meier analyses and Cox proportional hazard regression analyses were performed. 216/2517 patients died during a median 17.5 (interquartile range [IQR] 6.8-33.2) months of follow-up. 82/216 occurred within 6 months of starting ART. Adjusted hazard ratios were10. ...[more]

PMID: 28852017

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Project description:BackgroundThe failure to increase CD4 T-cell counts in some antiretroviral therapy suppressed participants (immunodiscordance) has been related to perturbed CD4 T-cell homeostasis and impacts clinical evolution.MethodsWe evaluated different definitions of immunodiscordance based on CD4 T-cell counts (cutoff) or CD4 T-cell increases from nadir value (?CD4) using supervised random forest classification of 74 immunological and clinical variables from 196 antiretroviral therapy suppressed individuals. Unsupervised clustering was performed using relevant variables identified in the supervised approach from 191 individuals.ResultsCutoff definition of CD4 cell count 400 cells/?l performed better than any other definition in segregating immunoconcordant and immunodiscordant individuals (85% accuracy), using markers of activation, nadir and death of CD4 T cells. Unsupervised clustering of relevant variables using this definition revealed large heterogeneity between immunodiscordant individuals and segregated participants into three distinct subgroups with distinct production, programmed cell-death protein-1 (PD-1) expression, activation and death of T cells. Surprisingly, a nonnegligible number of immunodiscordant participants (22%) showed high frequency of recent thymic emigrants and low CD4 T-cell activation and death, very similar to immunoconcordant participants. Notably, human leukocyte antigen - antigen D related (HLA-DR) PD-1 and CD45RA expression in CD4 T cells allowed reproducing subgroup segregation (81.4% accuracy). Despite sharp immunological differences, similar and persistently low CD4 values were maintained in these participants over time.ConclusionA cutoff value of CD4 T-cell count 400 cells/?l classified better immunodiscordant and immunoconcordant individuals than any ?CD4 classification. Immunodiscordance may present several, even opposite, immunological patterns that are identified by a simple immunological follow-up. Subgroup classification may help clinicians to delineate diverse approaches that may be needed to boost CD4 T-cell recovery.

Project description:Yunnan Province, China is thought to be the original source of biovar Orientalis of Yersinia pestis, the causative agent of the third plague pandemic that has spread globally since the end of the 19th century. Although encompassing a large area of natural plague foci, Y. pestis strains have rarely been found in live rodents during surveillance in Yunnan, and most isolates are from rodent corpses and their fleas. In 2017, 10 Y. pestis strains were isolated from seven live rodents and three fleas in Heqing County (HQ) of Yunnan. These strains were supposed to have low virulence to local rodents Eothenomys miletus and Apodemus chevrieri because the rodents were healthy and no dead animals were found in surrounding areas, as had occurred in previous epizootic disease. We performed microscopic and biochemical examinations of the isolates,and compared their whole-genome sequences and transcriptome with those of 10 high virulence Y. pestis strains that were isolated from the adjacent city (Lijiang). We analyzed the phenotypic, genomic, and transcriptomic characteristics of live rodent isolates. The isolates formed a previously undefined monophyletic branch of Y. pestis that was named 1.IN5. Six SNPs, two indels, and one copy number variation were detected between live rodent isolates and the high virulence neighbors. No obvious functional consequence of these variations was found according to the known annotation information. Among the genes that were differentially expressed between the live rodent isolates and their high virulence neighbors, we detected five iron transfer-related genes that were significantly up-regulated in live rodent isolates compared with high virulence isolates (|log2 (FC) | >1, p.adjust <0.05), indicating these genes may be related to the low-virulence phenotype. The novel genotype of Y. pestis reported here provides further insights into the evolution and spread of plague as well as clues that may help to decipher the virulence mechanism of this notorious pathogen.

Dataset Information

Prognosis of HIV Patients Receiving Antiretroviral Therapy According to CD4 Counts: A Long-term Follow-up study in Yunnan, China.

Publications

Prognosis of HIV Patients Receiving Antiretroviral Therapy According to CD4 Counts: A Long-term Follow-up study in Yunnan, China.

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