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Serum microRNAs in HIV-infected individuals as pre-diagnosis biomarkers for AIDS-NHL.

ABSTRACT: OBJECTIVE:To determine if changes in levels of serum microRNAs (miRNAs) were seen preceding the diagnosis of AIDS-related non-Hodgkin lymphoma (AIDS-NHL). DESIGN:Serum miRNA levels were compared in 3 subject groups from the Multicenter AIDS Cohort Study: HIV-negative men (n = 43), HIV-positive men who did not develop NHL (n = 45), and HIV-positive men before AIDS-NHL diagnosis (n = 62, median time before diagnosis, 8.8 months). METHODS:A total of 175 serum-enriched miRNAs were initially screened to identify differentially expressed miRNAs among these groups and the results validated by quantitative polymerase chain reaction. Receiver-operating characteristic analysis was then performed to assess biomarker utility. RESULTS:Higher levels of miR-21 and miR-122, and a lower level of miR-223, were able to discriminate HIV-infected from the HIV-uninfected groups, suggesting that these miRNAs are biomarkers for HIV infection but are not AIDS-NHL specific. Among the HIV-infected groups, a higher level of miR-222 was able to discriminate diffuse large B-cell lymphoma (DLBCL) and primary central nervous system lymphoma (PCNSL) subjects from HIV-infected subjects who did not develop NHL, with area under the receiver-operating characteristic curve of 0.777 and 0.792, respectively. At miR-222 cutoff values of 0.105 for DLBCL and 0.109 for PCNSL, the sensitivity and specificity were 75% and 77%, and 80% and 82%, respectively. CONCLUSIONS:Altered serum levels of miR-21, miR-122, and miR-223 are seen in HIV-infected individuals. Higher serum level of miR-222 has clear potential as a serum biomarker for earlier detection of DLBCL and PCNSL among HIV-infected individuals.

SUBMITTER: Thapa DR

PROVIDER: S-EPMC4096008 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Serum microRNAs in HIV-infected individuals as pre-diagnosis biomarkers for AIDS-NHL.

Thapa Dharma R DR Hussain Shehnaz K SK Tran Wen-Ching WC Dʼsouza Gypsyamber G Bream Jay H JH Achenback Chad J CJ Ayyavoo Velpandi V Detels Roger R Martínez-Maza Otoniel O

Journal of acquired immune deficiency syndromes (1999) 20140601 2

<h4>Objective</h4>To determine if changes in levels of serum microRNAs (miRNAs) were seen preceding the diagnosis of AIDS-related non-Hodgkin lymphoma (AIDS-NHL).<h4>Design</h4>Serum miRNA levels were compared in 3 subject groups from the Multicenter AIDS Cohort Study: HIV-negative men (n = 43), HIV-positive men who did not develop NHL (n = 45), and HIV-positive men before AIDS-NHL diagnosis (n = 62, median time before diagnosis, 8.8 months).<h4>Methods</h4>A total of 175 serum-enriched miRNAs w ...[more]

PMID: 24675587

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Project description:BackgroundWhether vexing clinical decision-making dilemmas can be partly addressed by recent advances in genomics is unclear. For example, when to initiate highly active antiretroviral therapy (HAART) during HIV-1 infection remains a clinical dilemma. This decision relies heavily on assessing AIDS risk based on the CD4+ T cell count and plasma viral load. However, the trajectories of these two laboratory markers are influenced, in part, by polymorphisms in CCR5, the major HIV coreceptor, and the gene copy number of CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine. Therefore, we determined whether accounting for both genetic and laboratory markers provided an improved means of assessing AIDS risk.Methods and findingsIn a prospective, single-site, ethnically-mixed cohort of 1,132 HIV-positive subjects, we determined the AIDS risk conveyed by the laboratory and genetic markers separately and in combination. Subjects were assigned to a low, moderate or high genetic risk group (GRG) based on variations in CCL3L1 and CCR5. The predictive value of the CCL3L1-CCR5 GRGs, as estimated by likelihood ratios, was equivalent to that of the laboratory markers. GRG status also predicted AIDS development when the laboratory markers conveyed a contrary risk. Additionally, in two separate and large groups of HIV+ subjects from a natural history cohort, the results from additive risk-scoring systems and classification and regression tree (CART) analysis revealed that the laboratory and CCL3L1-CCR5 genetic markers together provided more prognostic information than either marker alone. Furthermore, GRGs independently predicted the time interval from seroconversion to CD4+ cell count thresholds used to guide HAART initiation.ConclusionsThe combination of the laboratory and genetic markers captures a broader spectrum of AIDS risk than either marker alone. By tracking a unique aspect of AIDS risk distinct from that captured by the laboratory parameters, CCL3L1-CCR5 genotypes may have utility in HIV clinical management. These findings illustrate how genomic information might be applied to achieve practical benefits of personalized medicine.

Project description:In the USA, increased cerebrospinal fluid (CSF) inflammatory cytokines have been observed in antiretroviral therapy (ART)-naive, HIV-seropositive individuals with HIV-associated neurocognitive disorder (HAND). We characterized the relationship between HAND and CSF biomarker expression in ART-naive, HIV-seropositive individuals in Rakai, Uganda. We analyzed CSF of 78 HIV-seropositive, ART-naive Ugandan adults for 17 cytokines and 20 neurodegenerative biomarkers via Luminex multiplex assay. These adults underwent neurocognitive assessment to determine their degree of HAND. We compared biomarker concentrations between high and low CD4 groups and across HAND classifications, adjusting for multiple comparisons. Individuals with CD4 <200 cells/μL (N = 38) had elevated levels of CSF Interleukin (IL)-2, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF-α, matrix metalloproteinase (MMP)-1, MMP-7, and S100 calcium-binding protein B (S100B) and lower levels of amyloid β42. Individuals with CD4 351-500 cells/μL (N = 40) had significantly higher CSF levels of interleukin (IL)-1β, amyloid β42, and soluble receptor for advanced glycation end products (sRAGE). Increasing levels of S100B, platelet-derived growth factor-AA (PDGF-AA), brain-derived neurotrophic factor (BDNF), and sRAGE were associated with decreased odds of mild neurocognitive disorder (n = 22) or HIV-associated dementia (n = 15) compared with normal function (n = 30) or asymptomatic neurocognitive impairment (n = 11). Increased levels of interferon (IFN)-γ were associated with increased odds of mild neurocognitive impairment or HIV-associated dementia relative to normal or asymptomatic neurocognitive impairment. Proinflammatory CSF cytokines, chemokines, and neurodegenerative biomarkers were present in increasing concentrations with advanced immunosuppression and may play a role in the development of HAND. The presence of select CNS biomarkers may also play a protective role in the development of HAND.

Project description:BackgroundHIV is a major public health problem in the world, especially in sub-Saharan Africa. It often leads to loss of productive labour and disruption of existing social support system which results in deterioration of population health. This poses a great challenge to infected people in meeting their essential goods and services. This paper examines health and social support services provided by employers to HIV/AIDS infected employees in Tanzania.MethodsThis was a cross-sectional study, which employed qualitative and quantitative methods in data collection and analysis. Structured questionnaires and in-depth interviews were used to assess the health and social support services provision at employers and employees perspectives. The study participants were employees and employers from public and private organizations.ResultsA total of 181 employees and 23 employers from 23 workplaces aged between 18-68 years were involved. The results show that 23.8% (i.e., 20.4% males and 27.3% females) of the employees had at least one member of the family or close relatives living with HIV at the time of the study. Fifty six percent of the infected employees reported to have been receiving health or social support from their employers. Employees' responses were consistent with those reported by their employers. A total of 12(52.2%) and 11(47.8%) employers reported to have been providing health and social supports respectively. Female employees (58.3%) from the private sector (60.0%) were more likely to receive supports than male employees (52.6%) and than those from the public sector (46.2%). The most common health and social support received by the employees were treatment, and nutritional support and reduction of workload, respectively.ConclusionsHIV/AIDS infected employees named treatment and nutritional support, and soft loans and reduced workload respectively, as the most important health and social supports they needed from their employers. This study provides baseline information for further studies on provision of health and social support services by employers to HIV/AIDS infected employees in the context of a developing economy like Tanzania.

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Serum microRNAs in HIV-infected individuals as pre-diagnosis biomarkers for AIDS-NHL.

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Serum microRNAs in HIV-infected individuals as pre-diagnosis biomarkers for AIDS-NHL.

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