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Sample records for expression predicts hiv-associated

  1. Gene expression patterns associated with neurological disease in human HIV infection.

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    Pietro Paolo Sanna

    Full Text Available The pathogenesis and nosology of HIV-associated neurological disease (HAND remain incompletely understood. Here, to provide new insight into the molecular events leading to neurocognitive impairments (NCI in HIV infection, we analyzed pathway dysregulations in gene expression profiles of HIV-infected patients with or without NCI and HIV encephalitis (HIVE and control subjects. The Gene Set Enrichment Analysis (GSEA algorithm was used for pathway analyses in conjunction with the Molecular Signatures Database collection of canonical pathways (MSigDb. We analyzed pathway dysregulations in gene expression profiles of patients from the National NeuroAIDS Tissue Consortium (NNTC, which consists of samples from 3 different brain regions, including white matter, basal ganglia and frontal cortex of HIV-infected and control patients. While HIVE is characterized by widespread, uncontrolled inflammation and tissue damage, substantial gene expression evidence of induction of interferon (IFN, cytokines and tissue injury is apparent in all brain regions studied, even in the absence of NCI. Various degrees of white matter changes were present in all HIV-infected subjects and were the primary manifestation in patients with NCI in the absence of HIVE. In particular, NCI in patients without HIVE in the NNTC sample is associated with white matter expression of chemokines, cytokines and β-defensins, without significant activation of IFN. Altogether, the results identified distinct pathways differentially regulated over the course of neurological disease in HIV infection and provide a new perspective on the dynamics of pathogenic processes in the course of HIV neurological disease in humans. These results also demonstrate the power of the systems biology analyses and indicate that the establishment of larger human gene expression profile datasets will have the potential to provide novel mechanistic insight into the pathogenesis of neurological disease in HIV

  2. Increased brain-predicted aging in treated HIV disease.

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    Cole, James H; Underwood, Jonathan; Caan, Matthan W A; De Francesco, Davide; van Zoest, Rosan A; Leech, Robert; Wit, Ferdinand W N M; Portegies, Peter; Geurtsen, Gert J; Schmand, Ben A; Schim van der Loeff, Maarten F; Franceschi, Claudio; Sabin, Caroline A; Majoie, Charles B L M; Winston, Alan; Reiss, Peter; Sharp, David J

    2017-04-04

    To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. A large sample of virologically suppressed HIV-positive adults (n = 162, age 45-82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18-90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age - chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (-0.87 ± 8.40 years; b = 3.48, p brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  3. Circulating Cxcr5-Expressing Cd8+T-Cells are Major Producers of Il-21 and Associate with Limited Hiv Replication.

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    Perdomo-Celis, Federico; Taborda, Natalia A; Rugeles, Maria T

    2018-04-10

    Despite advances made with the highly active anti-retroviral therapy (HAART) in the control of the human immunodeficiency virus 1 (HIV) infection, a cure has not been achieved due to the persistence of viral reservoirs. The major HIV reservoirs remain in the lymphoid follicles due to, among other factors, the partial absence of CD8T-cells in these structures. Recently, lymphoid follicle-confined and circulating CD8T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) were described, possessing antiviral mechanisms which could help to control HIV replication. and methods: By flow cytometry, we characterized the phenotype and function of circulating CXCR5-expressing CD8T-cells in HIV-infected patients with natural or HAART-induced control of HIV replication. Circulating CXCR5-expressing CD8T-cells exhibited low or null expression of the C-C chemokine receptor type 7 (CCR7) and had a transitional memory phenotype. Particular redistributions of CXCR5-expressing CD8T-cells were found in HIV-infected patients, and they were partially restored by HAART. The frequency of CXCR5CCR7CD8T-cells was higher in spontaneous HIV controllers and negatively correlated with plasma HIV RNA levels. Total and HIV-specific CXCR5CD8T-cells were major producers of interleukin-21, and this function was positively associated with their interferon-γ production. Circulating CXCR5-expressing CD8T-cells are associated with low level HIV replication, could be novel correlates of protection and potentially useful in the eradication of HIV reservoirs.

  4. Perturbation of B Cell Gene Expression Persists in HIV-Infected Children Despite Effective Antiretroviral Therapy and Predicts H1N1 Response.

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    Cotugno, Nicola; De Armas, Lesley; Pallikkuth, Suresh; Rinaldi, Stefano; Issac, Biju; Cagigi, Alberto; Rossi, Paolo; Palma, Paolo; Pahwa, Savita

    2017-01-01

    Despite effective antiretroviral therapy (ART), HIV-infected individuals with apparently similar clinical and immunological characteristics can vary in responsiveness to vaccinations. However, molecular mechanisms responsible for such impairment, as well as biomarkers able to predict vaccine responsiveness in HIV-infected children, remain unknown. Following the hypothesis that a B cell qualitative impairment persists in HIV-infected children (HIV) despite effective ART and phenotypic B cell immune reconstitution, the aim of the current study was to investigate B cell gene expression of HIV compared to age-matched healthy controls (HCs) and to determine whether distinct gene expression patterns could predict the ability to respond to influenza vaccine. To do so, we analyzed prevaccination transcriptional levels of a 96-gene panel in equal numbers of sort-purified B cell subsets (SPBS) isolated from peripheral blood mononuclear cells using multiplexed RT-PCR. Immune responses to H1N1 antigen were determined by hemaglutination inhibition and memory B cell ELISpot assays following trivalent-inactivated influenza vaccination (TIV) for all study participants. Although there were no differences in terms of cell frequencies of SPBS between HIV and HC, the groups were distinguishable based upon gene expression analyses. Indeed, a 28-gene signature, characterized by higher expression of genes involved in the inflammatory response and immune activation was observed in activated memory B cells (CD27 + CD21 - ) from HIV when compared to HC despite long-term viral control (>24 months). Further analysis, taking into account H1N1 responses after TIV in HIV participants, revealed that a 25-gene signature in resting memory (RM) B cells (CD27 + CD21 + ) was able to distinguish vaccine responders from non-responders (NR). In fact, prevaccination RM B cells of responders showed a higher expression of gene sets involved in B cell adaptive immune responses ( APRIL, BTK, BLIMP1 ) and

  5. HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses.

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    Nathan Erdmann

    2015-08-01

    Full Text Available Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1 exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences and HLA-II allelic data, we identified 29 HLA-II associated HIV sequence polymorphisms or adaptations (HLA-AP in an African cohort of chronically HIV-infected individuals. Epitopes encompassing the predicted adaptation (AE or its non-adapted (NAE version were evaluated for immunogenicity. Using a CD8-depleted IFN-γ ELISpot assay, we determined that the magnitude of CD4+ T cell responses to the predicted epitopes in controllers was higher compared to non-controllers (p<0.0001. However, regardless of the group, the magnitude of responses to AE was lower as compared to NAE (p<0.0001. CD4+ T cell responses in patients with acute HIV infection (AHI demonstrated poor immunogenicity towards AE as compared to NAE encoded by their transmitted founder virus. Longitudinal data in AHI off antiretroviral therapy demonstrated sequence changes that were biologically confirmed to represent CD4+ escape mutations. These data demonstrate an innovative application of HLA-associated polymorphisms to identify biologically relevant CD4+ epitopes and suggests CD4+ T cells are active participants in driving HIV evolution.

  6. Decreased Fc receptor expression on innate immune cells is associated with impaired antibody-mediated cellular phagocytic activity in chronically HIV-1 infected individuals.

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    Dugast, Anne-Sophie; Tonelli, Andrew; Berger, Christoph T; Ackerman, Margaret E; Sciaranghella, Gaia; Liu, Qingquan; Sips, Magdalena; Toth, Ildiko; Piechocka-Trocha, Alicja; Ghebremichael, Musie; Alter, Galit

    2011-07-05

    In addition to neutralization, antibodies mediate other antiviral activities including antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), as well as complement deposition. While it is established that progressive HIV infection is associated with reduced ADCC and ADCP, the underlying mechanism for this loss of function is unknown. Here we report considerable changes in FcR expression over the course of HIV infection on both mDCs and monocytes, including elevated FcγRI expression in acute HIV infection and reduced expression of FcγRII and FcγRIIIa in chronic HIV infection. Furthermore, selective blockade of FcγRII alone was associated with a loss in ADCP activity, suggesting that FcγRII plays a central role in modulating ADCP. Overall, HIV infection is associated with a number of changes in FcR expression on phagocytic cells that are associated with changes in their ability to respond to antibody-opsonized targets, potentially contributing to a failure in viral clearance in progressive HIV-1 infection. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Decreased Fc-Receptor expression on innate immune cells is associated with impaired antibody mediated cellular phagocytic activity in chronically HIV-1 infected individuals

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    Dugast, Anne-Sophie; Tonelli, Andrew; Berger, Christoph T.; Ackerman, Margaret E.; Sciaranghella, Gaia; Liu, Qingquan; Sips, Magdalena; Toth, Ildiko; Piechocka-Trocha, Alicja; Ghebremichael, Musie; Alter, Galit

    2011-01-01

    In addition to neutralization, antibodies mediate other antiviral activities including antibody-dependent cellular-phagocytosis (ADCP), antibody dependent cellular-cytotoxicity (ADCC), as well as complement deposition. While it is established that progressive HIV infection is associated with reduced ADCC and ADCP, the underlying mechanism for this loss of function is unknown. Here we report considerable changes in FcR expression over the course of HIV infection on both mDCs and monocytes, including elevated FcγRI expression in acute HIV infection and reduced expression of FcγRII and FcγRIIIa in chronic HIV infection. Furthermore, selective blockade of FcγRII alone was associated with a loss in ADCP activity, suggesting that FcγRII plays a central role in modulating ADCP. Overall, HIV infection is associated with a number of changes in FcR expression on phagocytic cells that are associated with changes in their ability to respond to antibody-opsonized targets, potentially contributing to a failure in viral clearance in progressive HIV-1 infection. PMID:21565376

  8. Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice

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    Kesby, James P.; Markou, Athina; Semenova, Svetlana

    2014-01-01

    Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e., similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. PMID:25476577

  9. Focal glomerulosclerosis in proviral and c-fms transgenic mice links Vpr expression to HIV-associated nephropathy

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    Dickie, Peter; Roberts, Amanda; Uwiera, Richard; Witmer, Jennifer; Sharma, Kirti; Kopp, Jeffrey B.

    2004-01-01

    Clinical and morphologic features of human immunodeficiency virus (HIV)-associated nephropathy (HIVAN), such as proteinuria, sclerosing glomerulopathy, tubular degeneration, and interstitial disease, have been modeled in mice bearing an HIV proviral transgene rendered noninfectious through a deletion in gag/pol. Exploring the genetic basis of HIVAN, HIV transgenic mice bearing mutations in either or both of the accessory genes nef and vpr were created. Proteinuria and focal glomerulosclerosis (FGS) only developed in mice with an intact vpr gene. Transgenic mice bearing a simplified proviral DNA (encoding only Tat and Vpr) developed renal disease characterized by FGS in which Vpr protein was localized to glomerular and tubular epithelia by immunohistochemistry. The dual transgenic progeny of HIV[Tat/Vpr] mice bred to HIV[ΔVpr] proviral transgenic mice displayed a more severe nephropathy with no apparent increase in Vpr expression, implying that multiple viral genes contribute to HIVAN. However, the unique contribution of macrophage-specific Vpr expression in the development of glomerular disease was underscored by the induction of FGS in multiple murine lines bearing a c-fms/vpr transgene

  10. Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder

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    2014-01-01

    Background HIV-associated neurocognitive disorder (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occurs in approximately 50% of HIV infected individuals. In the United States, the prevalence of cigarette smoking ranges from 35-70% in HIV-infected individuals compared to 20% in general population. Cognitive impairment in heavy cigarette smokers has been well reported. However, the synergistic effects of nicotine and HIV infection and the underlying mechanisms in the development of HAND are unknown. Results In this study, we explored the role of nicotine in the progression of HAND using SK-N-MC, a neuronal cell line. SK-N-MC cells were infected with HIV-1 in the presence or absence of nicotine for 7 days. We observed significant increase in HIV infectivity in SK-N-MC treated with nicotine compared to untreated HIV-infected neuronal cells. HIV and nicotine synergize to significantly dysregulate the expression of synaptic plasticity genes and spine density; with a concomitant increase of HDAC2 levels in SK-N-MC cells. In addition, inhibition of HDAC2 up-regulation with the use of vorinostat resulted in HIV latency breakdown and recovery of synaptic plasticity genes expression and spine density in nicotine/HIV alone and in co-treated SK-N-MC cells. Furthermore, increased eIF2 alpha phosphorylation, which negatively regulates eukaryotic translational process, was observed in HIV alone and in co-treatment with nicotine compared to untreated control and nicotine alone treated SK-N-MC cells. Conclusions These results suggest that nicotine and HIV synergize to negatively regulate the synaptic plasticity gene expression and spine density and this may contribute to the increased risk of HAND in HIV infected smokers. Apart from disrupting latency, vorinostat may be a useful therapeutic to inhibit the negative regulatory effects on synaptic plasticity in HIV infected nicotine abusers. PMID:24886748

  11. Upper Gastrointestinal Symptoms Predictive of Candida Esophagitis and Erosive Esophagitis in HIV and Non-HIV Patients

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    Takahashi, Yuta; Nagata, Naoyoshi; Shimbo, Takuro; Nishijima, Takeshi; Watanabe, Koji; Aoki, Tomonori; Sekine, Katsunori; Okubo, Hidetaka; Watanabe, Kazuhiro; Sakurai, Toshiyuki; Yokoi, Chizu; Mimori, Akio; Oka, Shinichi; Uemura, Naomi; Akiyama, Junichi

    2015-01-01

    Abstract Upper gastrointestinal (GI) symptoms are common in both HIV and non-HIV-infected patients, but the difference of GI symptom severity between 2 groups remains unknown. Candida esophagitis and erosive esophagitis, 2 major types of esophagitis, are seen in both HIV and non-HIV-infected patients, but differences in GI symptoms that are predictive of esophagitis between 2 groups remain unknown. We aimed to determine whether GI symptoms differ between HIV-infected and non-HIV-infected patients, and identify specific symptoms of candida esophagitis and erosive esophagitis between 2 groups. We prospectively enrolled 6011 patients (HIV, 430; non-HIV, 5581) who underwent endoscopy and completed questionnaires. Nine upper GI symptoms (epigastric pain, heartburn, acid regurgitation, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia) were evaluated using a 7-point Likert scale. Associations between esophagitis and symptoms were analyzed by the multivariate logistic regression model adjusted for age, sex, and proton pump inhibitors. Endoscopy revealed GI-organic diseases in 33.4% (2010/6.011) of patients. The prevalence of candida esophagitis and erosive esophagitis was 11.2% and 12.1% in HIV-infected patients, respectively, whereas it was 2.9% and 10.7 % in non-HIV-infected patients, respectively. After excluding GI-organic diseases, HIV-infected patients had significantly (P symptom scores for heartburn, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia than non-HIV-infected patients. In HIV-infected patients, any symptom was not significantly associated with CD4 cell count. In multivariate analysis, none of the 9 GI symptoms were associated with candida esophagitis in HIV-infected patients, whereas dysphagia and odynophagia were independently (P HIV-infected patients. However, heartburn and acid regurgitation were independently (P symptom scores were reliable in both HIV (α, 0.86) and non-HIV-infected patients

  12. Possible Biomarkers for the Early Detection of HIV-associated Heart Diseases: A Proteomics and Bioinformatics Prediction

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    Suraiya Rasheed

    2015-01-01

    Full Text Available The frequency of cardiovascular disorders is increasing in HIV-infected individuals despite a significant reduction in the viral load by antiretroviral therapies (ART. Since the CD4+ T-cells are responsible for the viral load as well as immunological responses, we hypothesized that chronic HIV-infection of T-cells produces novel proteins/enzymes that cause cardiac dysfunctions. To identify specific factors that might cause cardiac disorders without the influence of numerous cofactors produced by other pathogenic microorganisms that co-inhabit most HIV-infected individuals, we analyzed genome-wide proteomes of a CD4+ T-cell line at different stages of HIV replication and cell growth over >6 months. Subtractive analyses of several hundred differentially regulated proteins from HIV-infected and uninfected counterpart cells and comparisons with proteins expressed from the same cells after treating with the antiviral drug Zidovudine/AZT and inhibiting virus replication, identified a well-coordinated network of 12 soluble/diffusible proteins in HIV-infected cells. Functional categorization, bioinformatics and statistical analyses of each protein predicted that the expression of cardiac-specific Ca2+ kinase together with multiple Ca2+ release channels causes a sustained overload of Ca2+ in the heart which induces fetal/cardiac myosin heavy chains (MYH6 and MYH7 and a myosin light-chain kinase. Each of these proteins has been shown to cause cardiac stress, arrhythmia, hypertrophic signaling, cardiomyopathy and heart failure (p = 8 × 10−11. Translational studies using the newly discovered proteins produced by HIV infection alone would provide additional biomarkers that could be added to the conventional markers for an early diagnosis and/or development of specific therapeutic interventions for heart diseases in HIV-infected individuals.

  13. Relationship between expressed HIV/AIDS-related stigma and HIV-beliefs/knowledge and behaviour in families of HIV infected children in Kenya.

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    Hamra, Mary; Ross, Michael W; Orrs, Mark; D'Agostino, Angelo

    2006-04-01

    To quantify expressed stigma in clients of the Kangemi program for HIV+ children, and to characterize the association between stigma and other population characteristics. By means of a household survey we created a stigma index and indices for other social and knowledge domains that influence HIV-related healthcare. We used chi2, anova, and correlation to identify associations between domains. The mean (+/-SD) expressed stigma on a six points scale (6 = least stigma) was 3.65 +/- 1.64. Composite scores on knowledge about AIDS were skewed toward more knowledge; and analysis of individual knowledge items indicates that most respondents reject erroneous traditional beliefs and myths about the causes and transmission routes of AIDS. Respondents who were younger, had never married, and had less education expressed greater stigma. Differences in stigma were associated with poor knowledge about AIDS and negative attitudes toward testing, but not with gender or tribal affiliation. Condom use at last intercourse, unrelated to stigma, was only 40% (n = 218). While this population has good knowledge about AIDS and appraises risks realistically, it fails to reduce these risks. Associations between stigma and other domains can inform interventions that improve HIV care and mitigate spread of HIV.

  14. Influence of HLA-C Expression Level on HIV Control

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    Apps, Richard; Qi, Ying; Carlson, Jonathan M.; Chen, Haoyan; Gao, Xiaojiang; Thomas, Rasmi; Yuki, Yuko; Del Prete, Greg Q.; Goulder, Philip; Brumme, Zabrina L.; Brumme, Chanson J.; John, Mina; Mallal, Simon; Nelson, George; Bosch, Ronald; Heckerman, David; Stein, Judy L.; Soderberg, Kelly A.; Moody, M. Anthony; Denny, Thomas N.; Zeng, Xue; Fang, Jingyuan; Moffett, Ashley; Lifson, Jeffrey D.; Goedert, James J.; Buchbinder, Susan; Kirk, Gregory D.; Fellay, Jacques; McLaren, Paul; Deeks, Steven G.; Pereyra, Florencia; Walker, Bruce; Michael, Nelson L.; Weintrob, Amy; Wolinsky, Steven; Liao, Wilson; Carrington, Mary

    2013-01-01

    A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn’s disease, suggesting a broader influence of HLA expression levels in human disease. PMID:23559252

  15. Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells.

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    Ramsuran, Veron; Naranbhai, Vivek; Horowitz, Amir; Qi, Ying; Martin, Maureen P; Yuki, Yuko; Gao, Xiaojiang; Walker-Sperling, Victoria; Del Prete, Gregory Q; Schneider, Douglas K; Lifson, Jeffrey D; Fellay, Jacques; Deeks, Steven G; Martin, Jeffrey N; Goedert, James J; Wolinsky, Steven M; Michael, Nelson L; Kirk, Gregory D; Buchbinder, Susan; Haas, David; Ndung'u, Thumbi; Goulder, Philip; Parham, Peter; Walker, Bruce D; Carlson, Jonathan M; Carrington, Mary

    2018-01-05

    The highly polymorphic human leukocyte antigen ( HLA ) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference. Analysis of 9763 HIV-infected individuals from 21 cohorts shows that higher HLA-A levels confer poorer control of HIV. Elevated HLA-A expression provides enhanced levels of an HLA-A-derived signal peptide that specifically binds and determines expression levels of HLA-E, the ligand for the inhibitory NKG2A natural killer (NK) cell receptor. HLA-B haplotypes that favor NKG2A-mediated NK cell licensing (i.e., education) exacerbate the deleterious effect of high HLA-A on HIV control, consistent with NKG2A-mediated inhibition impairing NK cell clearance of HIV-infected targets. Therapeutic blockade of HLA-E:NKG2A interaction may yield benefit in HIV disease. Copyright © 2017, American Association for the Advancement of Science.

  16. Sialoadhesin expressed on IFN-induced monocytes binds HIV-1 and enhances infectivity.

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    Hans Rempel

    2008-04-01

    Full Text Available HIV-1 infection dysregulates the immune system and alters gene expression in circulating monocytes. Differential gene expression analysis of CD14(+ monocytes from subjects infected with HIV-1 revealed increased expression of sialoadhesin (Sn, CD169, Siglec 1, a cell adhesion molecule first described in a subset of macrophages activated in chronic inflammatory diseases.We analyzed sialoadhesin expression on CD14(+ monocytes by flow cytometry and found significantly higher expression in subjects with elevated viral loads compared to subjects with undetectable viral loads. In cultured CD14(+ monocytes isolated from healthy individuals, sialoadhesin expression was induced by interferon-alpha and interferon-gamma but not tumor necrosis factor-alpha. Using a stringent binding assay, sialoadhesin-expressing monocytes adsorbed HIV-1 through interaction with the sialic acid residues on the viral envelope glycoprotein gp120. Furthermore, monocytes expressing sialoadhesin facilitated HIV-1 trans infection of permissive cells, which occurred in the absence of monocyte self-infection.Increased sialoadhesin expression on CD14(+ monocytes occurred in response to HIV-1 infection with maximum expression associated with high viral load. We show that interferons induce sialoadhesin in primary CD14(+ monocytes, which is consistent with an antiviral response during viremia. Our findings suggest that circulating sialoadhesin-expressing monocytes are capable of binding HIV-1 and effectively delivering virus to target cells thereby enhancing the distribution of HIV-1. Sialoadhesin could disseminate HIV-1 to viral reservoirs during monocyte immunosurveillance or migration to sites of inflammation and then facilitate HIV-1 infection of permissive cells.

  17. Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors.

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    Perdigão, Pedro; Gaj, Thomas; Santa-Marta, Mariana; Barbas, Carlos F; Goncalves, Joao

    2016-01-01

    The presence of replication-competent HIV-1 -which resides mainly in resting CD4+ T cells--is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE) proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection.

  18. Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors.

    Directory of Open Access Journals (Sweden)

    Pedro Perdigão

    Full Text Available The presence of replication-competent HIV-1 -which resides mainly in resting CD4+ T cells--is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection.

  19. HIV subtype influences HLA-B*07:02-associated HIV disease outcome

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    Kløverpris, Henrik N; Adland, Emily; Koyanagi, Madoka

    2014-01-01

    Genetic polymorphisms within the MHC encoding region have the strongest impact on HIV disease progression of any in the human genome and provide important clues to the mechanisms of HIV immune control. Few analyses have been undertaken of HLA alleles associated with rapid disease progression. HLA......% versus 43% in HLA-B*07:02-negative subjects). These data support earlier studies suggesting that increased breadth of the Gag-specific CD8(+) T cell response may contribute to improved HIV immune control irrespective of the particular HLA molecules expressed....

  20. CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells.

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    Abdel-Mohsen, Mohamed; Kuri-Cervantes, Leticia; Grau-Exposito, Judith; Spivak, Adam M; Nell, Racheal A; Tomescu, Costin; Vadrevu, Surya Kumari; Giron, Leila B; Serra-Peinado, Carla; Genescà, Meritxell; Castellví, Josep; Wu, Guoxin; Del Rio Estrada, Perla M; González-Navarro, Mauricio; Lynn, Kenneth; King, Colin T; Vemula, Sai; Cox, Kara; Wan, Yanmin; Li, Qingsheng; Mounzer, Karam; Kostman, Jay; Frank, Ian; Paiardini, Mirko; Hazuda, Daria; Reyes-Terán, Gustavo; Richman, Douglas; Howell, Bonnie; Tebas, Pablo; Martinez-Picado, Javier; Planelles, Vicente; Buzon, Maria J; Betts, Michael R; Montaner, Luis J

    2018-04-18

    The persistence of HIV reservoirs, including latently infected, resting CD4 + T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4 + T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4 + T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV + or SIV + subjects, we found that most of the circulating memory CD32 + CD4 + T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a T H 2 phenotype as defined by CXCR3, CCR4, and CCR6. CD32 expression did not selectively enrich for HIV- or SIV-infected CD4 + T cells in peripheral blood or lymphoid tissue; isolated CD32 + resting CD4 + T cells accounted for less than 3% of the total HIV DNA in CD4 + T cells. Cell-associated HIV DNA and RNA loads in CD4 + T cells positively correlated with the frequency of CD32 + CD69 + CD4 + T cells but not with CD32 expression on resting CD4 + T cells. Using RNA fluorescence in situ hybridization, CD32 coexpression with HIV RNA or p24 was detected after in vitro HIV infection (peripheral blood mononuclear cell and tissue) and in vivo within lymph node tissue from HIV-infected individuals. Together, these results indicate that CD32 is not a marker of resting CD4 + T cells or of enriched HIV DNA-positive cells after ART; rather, CD32 is predominately expressed on a subset of activated CD4 + T cells enriched for transcriptionally active HIV after long-term ART. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  1. HIV-1 DNA predicts disease progression and post-treatment virological control

    Science.gov (United States)

    Williams, James P; Hurst, Jacob; Stöhr, Wolfgang; Robinson, Nicola; Brown, Helen; Fisher, Martin; Kinloch, Sabine; Cooper, David; Schechter, Mauro; Tambussi, Giuseppe; Fidler, Sarah; Carrington, Mary; Babiker, Abdel; Weber, Jonathan

    2014-01-01

    In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials. Clinical trial registration: ISRCTN76742797 and EudraCT2004-000446-20 DOI: http://dx.doi.org/10.7554/eLife.03821.001 PMID:25217531

  2. Prediction of Associations between microRNAs and Gene Expression in Glioma Biology.

    Directory of Open Access Journals (Sweden)

    Stefan Wuchty

    Full Text Available Despite progress in the determination of miR interactions, their regulatory role in cancer is only beginning to be unraveled. Utilizing gene expression data from 27 glioblastoma samples we found that the mere knowledge of physical interactions between specific mRNAs and miRs can be used to determine associated regulatory interactions, allowing us to identify 626 associated interactions, involving 128 miRs that putatively modulate the expression of 246 mRNAs. Experimentally determining the expression of miRs, we found an over-representation of over(under-expressed miRs with various predicted mRNA target sequences. Such significantly associated miRs that putatively bind over-expressed genes strongly tend to have binding sites nearby the 3'UTR of the corresponding mRNAs, suggesting that the presence of the miRs near the translation stop site may be a factor in their regulatory ability. Our analysis predicted a significant association between miR-128 and the protein kinase WEE1, which we subsequently validated experimentally by showing that the over-expression of the naturally under-expressed miR-128 in glioma cells resulted in the inhibition of WEE1 in glioblastoma cells.

  3. Predicting the short-term risk of diabetes in HIV-positive patients

    DEFF Research Database (Denmark)

    Petoumenos, Kathy; Worm, Signe Westring; Fontas, Eric

    2012-01-01

    Introduction: HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM ......). Factors predictive of DM included higher glucose, body mass index (BMI) and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of...... and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV...

  4. Cytokine expression of macrophages in HIV-1-associated vacuolar myelopathy.

    Science.gov (United States)

    Tyor, W R; Glass, J D; Baumrind, N; McArthur, J C; Griffin, J W; Becker, P S; Griffin, D E

    1993-05-01

    Macrophages are frequently present within the periaxonal and intramyelinic vacuoles that are located primarily in the posterior and lateral funiculi of the thoracic spinal cord in HIV-associated vacuolar myelopathy. But the role of these macrophages in the formation of the vacuoles is unclear. One hypothesis is that cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF)-alpha, are produced locally by macrophages and have toxic effects on myelin or oligodendrocytes. The resulting myelin damage eventually culminates in the removal of myelin by macrophages and vacuole formation. We studied thoracic spinal cord specimens taken at autopsy from HIV-positive (+) and HIV-negative individuals. The predominant mononuclear cells present in HIV+ spinal cords are macrophages. They are located primarily in the posterior and lateral funiculi regardless of the presence or absence of vacuolar myelopathy. Macrophages and microglia are more frequent in HIV+ than HIV-negative individuals and these cells frequently stain for class I and class II antigens, IL-1, and TNF-alpha. Activated macrophages positive for IL-1 and TNF-alpha are great increased in the posterior and lateral funiculi of HIV+ individuals with and without vacuolar myelopathy, suggesting they are present prior to the development of vacuoles. Cytokines, such as TNF-alpha, may be toxic for myelin or oligodendrocytes, leading to myelin damage and removal by macrophages and vacuole formation.

  5. Network-based prediction and analysis of HIV dependency factors.

    Directory of Open Access Journals (Sweden)

    T M Murali

    2011-09-01

    Full Text Available HIV Dependency Factors (HDFs are a class of human proteins that are essential for HIV replication, but are not lethal to the host cell when silenced. Three previous genome-wide RNAi experiments identified HDF sets with little overlap. We combine data from these three studies with a human protein interaction network to predict new HDFs, using an intuitive algorithm called SinkSource and four other algorithms published in the literature. Our algorithm achieves high precision and recall upon cross validation, as do the other methods. A number of HDFs that we predict are known to interact with HIV proteins. They belong to multiple protein complexes and biological processes that are known to be manipulated by HIV. We also demonstrate that many predicted HDF genes show significantly different programs of expression in early response to SIV infection in two non-human primate species that differ in AIDS progression. Our results suggest that many HDFs are yet to be discovered and that they have potential value as prognostic markers to determine pathological outcome and the likelihood of AIDS development. More generally, if multiple genome-wide gene-level studies have been performed at independent labs to study the same biological system or phenomenon, our methodology is applicable to interpret these studies simultaneously in the context of molecular interaction networks and to ask if they reinforce or contradict each other.

  6. HIV-1 impairs human retinal pigment epithelial barrier function: possible association with the pathogenesis of HIV-associated retinopathy.

    Science.gov (United States)

    Tan, Suiyi; Duan, Heng; Xun, Tianrong; Ci, Wei; Qiu, Jiayin; Yu, Fei; Zhao, Xuyan; Wu, Linxuan; Li, Lin; Lu, Lu; Jiang, Shibo; Liu, Shuwen

    2014-07-01

    The breakdown of human retinal pigment epithelial (HRPE) barrier is considered as the etiology of retinopathy, which affects the quality of life of HIV/AIDS patients. Here we demonstrate that HIV-1 could directly impair HRPE barrier function, which leads to the translocation of HIV-1 and bacteria. HRPE cells (D407) were grown to form polarized, confluent monolayers and treated with different HIV-1 infectious clones. A significant increase of monolayer permeability, as measured by trans-epithelial electrical resistance (TEER) and apical-basolateral movements of sodium fluorescein, was observed. Disrupted tightness of HRPE barrier was associated with the downregulation of several tight junction proteins in D407 cells, including ZO-1, Occludin, Claudin-1, Claudin-2, Claudin-3, Claudin-4, and Claudin-5, after exposure to HIV-1, without affecting the viability of cells. HIV-1 gp120 was shown to participate in the alteration of barrier properties, as evidenced by decreased TEER and weakened expression of tight junction proteins in D407 monolayers after exposure to pseudotyped HIV-1, UV-inactivated HIV-1, and free gp120, but not to an envelope (Env)-defective mutant of HIV. Furthermore, exposure to HIV-1 particles could induce the release of pro-inflammatory cytokines in D407, including IL-6 and MCP-1, both of which downregulated the expression of ZO-1 in the HRPE barrier. Disrupted HRPE monolayer allowed translocation of HIV-1 and bacteria across the epithelium. Overall, these findings suggest that HIV-1 may exploit its Env glycoprotein to induce an inflammatory state in HRPE cells, which could result in impairment of HRPE monolayer integrity, allowing virus and bacteria existing in ocular fluids to cross the epithelium and penetrate the HRPE barrier. Our study highlights the role of HIV-1 in the pathogenesis of HIV/AIDS-related retinopathy and suggests potential therapeutic targets for this ocular complication.

  7. Urinary NGAL marks cystic disease in HIV-associated nephropathy.

    Science.gov (United States)

    Paragas, Neal; Nickolas, Thomas L; Wyatt, Christina; Forster, Catherine S; Sise, Meghan; Morgello, Susan; Jagla, Bernd; Buchen, Charles; Stella, Peter; Sanna-Cherchi, Simone; Carnevali, Maria Luisa; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Schmidt-Ott, Kai M; Allegri, Landino; Klotman, Paul; D'Agati, Vivette; Gharavi, Ali G; Barasch, Jonathan

    2009-08-01

    Nephrosis and a rapid decline in kidney function characterize HIV-associated nephropathy (HIVAN). Histologically, HIVAN is a collapsing focal segmental glomerulosclerosis with prominent tubular damage. We explored the expression of neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular injury, to determine whether this protein has the potential to aid in the noninvasive diagnosis of HIVAN. We found that expression of urinary NGAL was much higher in patients with biopsy-proven HIVAN than in HIV-positive and HIV-negative patients with other forms of chronic kidney disease. In the HIV-transgenic mouse model of HIVAN, NGAL mRNA was abundant in dilated, microcystic segments of the nephron. In contrast, urinary NGAL did not correlate with proteinuria in human or in mouse models. These data show that marked upregulation of NGAL accompanies HIVAN and support further study of uNGAL levels in large cohorts to aid in the noninvasive diagnosis of HIVAN and screen for HIVAN-related tubular damage.

  8. The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation.

    Science.gov (United States)

    Feeney, Eoin R; McAuley, Nuala; O'Halloran, Jane A; Rock, Clare; Low, Justin; Satchell, Claudette S; Lambert, John S; Sheehan, Gerald J; Mallon, Patrick W G

    2013-02-15

    Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular risk and reduced high-density lipoprotein cholesterol (HDL-c). In vitro, HIV impairs monocyte-macrophage cholesterol efflux, a major determinant of circulating HDL-c, by increasing ABCA1 degradation, with compensatory upregulation of ABCA1 messenger RNA (mRNA). We examined expression of genes involved in cholesterol uptake, metabolism, and efflux in monocytes from 22 HIV-positive subjects on antiretroviral therapy (ART-Treated), 30 untreated HIV-positive subjects (ART-Naive), and 22 HIV-negative controls (HIV-Neg). HDL-c was lower and expression of ABCA1 mRNA was higher in ART-Naive subjects than in both ART-Treated and HIV-Neg subjects (both P ART-Treated and ART-Naive subjects than in HIV-Neg controls. In vivo, increased monocyte ABCA1 expression in untreated HIV-infected patients and normalization of ABCA1 expression with virological suppression by ART supports direct HIV-induced impairment of cholesterol efflux previously demonstrated in vitro. However, decreased expression of cholesterol sensing, uptake, and synthesis genes in both untreated and treated HIV infection suggests that both HIV and ART affect monocyte cholesterol metabolism in a pattern consistent with accumulation of intramonocyte cholesterol.

  9. Differentially-Expressed Pseudogenes in HIV-1 Infection

    Directory of Open Access Journals (Sweden)

    Aditi Gupta

    2015-09-01

    Full Text Available Not all pseudogenes are transcriptionally silent as previously thought. Pseudogene transcripts, although not translated, contribute to the non-coding RNA pool of the cell that regulates the expression of other genes. Pseudogene transcripts can also directly compete with the parent gene transcripts for mRNA stability and other cell factors, modulating their expression levels. Tissue-specific and cancer-specific differential expression of these “functional” pseudogenes has been reported. To ascertain potential pseudogene:gene interactions in HIV-1 infection, we analyzed transcriptomes from infected and uninfected T-cells and found that 21 pseudogenes are differentially expressed in HIV-1 infection. This is interesting because parent genes of one-third of these differentially-expressed pseudogenes are implicated in HIV-1 life cycle, and parent genes of half of these pseudogenes are involved in different viral infections. Our bioinformatics analysis identifies candidate pseudogene:gene interactions that may be of significance in HIV-1 infection. Experimental validation of these interactions would establish that retroviruses exploit this newly-discovered layer of host gene expression regulation for their own benefit.

  10. Differentially-Expressed Pseudogenes in HIV-1 Infection.

    Science.gov (United States)

    Gupta, Aditi; Brown, C Titus; Zheng, Yong-Hui; Adami, Christoph

    2015-09-29

    Not all pseudogenes are transcriptionally silent as previously thought. Pseudogene transcripts, although not translated, contribute to the non-coding RNA pool of the cell that regulates the expression of other genes. Pseudogene transcripts can also directly compete with the parent gene transcripts for mRNA stability and other cell factors, modulating their expression levels. Tissue-specific and cancer-specific differential expression of these "functional" pseudogenes has been reported. To ascertain potential pseudogene:gene interactions in HIV-1 infection, we analyzed transcriptomes from infected and uninfected T-cells and found that 21 pseudogenes are differentially expressed in HIV-1 infection. This is interesting because parent genes of one-third of these differentially-expressed pseudogenes are implicated in HIV-1 life cycle, and parent genes of half of these pseudogenes are involved in different viral infections. Our bioinformatics analysis identifies candidate pseudogene:gene interactions that may be of significance in HIV-1 infection. Experimental validation of these interactions would establish that retroviruses exploit this newly-discovered layer of host gene expression regulation for their own benefit.

  11. Predicting the short-term risk of diabetes in HIV-positive patients

    DEFF Research Database (Denmark)

    Petoumenos, Kathy; Worm, Signe W; Fontas, Eric

    2012-01-01

    HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM and other...... glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV...

  12. Upper Gastrointestinal Symptoms Predictive of Candida Esophagitis and Erosive Esophagitis in HIV and Non-HIV Patients: An Endoscopy-Based Cross-Sectional Study of 6011 Patients.

    Science.gov (United States)

    Takahashi, Yuta; Nagata, Naoyoshi; Shimbo, Takuro; Nishijima, Takeshi; Watanabe, Koji; Aoki, Tomonori; Sekine, Katsunori; Okubo, Hidetaka; Watanabe, Kazuhiro; Sakurai, Toshiyuki; Yokoi, Chizu; Mimori, Akio; Oka, Shinichi; Uemura, Naomi; Akiyama, Junichi

    2015-11-01

    Upper gastrointestinal (GI) symptoms are common in both HIV and non-HIV-infected patients, but the difference of GI symptom severity between 2 groups remains unknown. Candida esophagitis and erosive esophagitis, 2 major types of esophagitis, are seen in both HIV and non-HIV-infected patients, but differences in GI symptoms that are predictive of esophagitis between 2 groups remain unknown. We aimed to determine whether GI symptoms differ between HIV-infected and non-HIV-infected patients, and identify specific symptoms of candida esophagitis and erosive esophagitis between 2 groups.We prospectively enrolled 6011 patients (HIV, 430; non-HIV, 5581) who underwent endoscopy and completed questionnaires. Nine upper GI symptoms (epigastric pain, heartburn, acid regurgitation, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia) were evaluated using a 7-point Likert scale. Associations between esophagitis and symptoms were analyzed by the multivariate logistic regression model adjusted for age, sex, and proton pump inhibitors.Endoscopy revealed GI-organic diseases in 33.4% (2010/6.011) of patients. The prevalence of candida esophagitis and erosive esophagitis was 11.2% and 12.1% in HIV-infected patients, respectively, whereas it was 2.9% and 10.7 % in non-HIV-infected patients, respectively. After excluding GI-organic diseases, HIV-infected patients had significantly (P symptom scores for heartburn, hunger cramps, nausea, early satiety, belching, dysphagia, and odynophagia than non-HIV-infected patients. In HIV-infected patients, any symptom was not significantly associated with CD4 cell count. In multivariate analysis, none of the 9 GI symptoms were associated with candida esophagitis in HIV-infected patients, whereas dysphagia and odynophagia were independently (P HIV-infected patients. However, heartburn and acid regurgitation were independently (P symptom scores were reliable in both HIV (α, 0.86) and non-HIV-infected patients (α, 0.85).This

  13. Seroconversion for human herpesvirus 8 during HIV infection is highly predictive of Kaposi's sarcoma

    NARCIS (Netherlands)

    Renwick, N.; Halaby, T.; Weverling, G. J.; Dukers, N. H.; Simpson, G. R.; Coutinho, R. A.; Lange, J. M.; Schulz, T. F.; Goudsmit, J.

    1998-01-01

    The finding of antibodies against human herpesvirus 8 (HHV-8) is associated with the occurrence of Kaposi's sarcoma in persons infected with HIV. However, the predictive value of HHV-8 antibodies for Kaposi's sarcoma in HIV infection is unknown. The Amsterdam Cohort Studies on HIV infection and AIDS

  14. Integrated and Total HIV-1 DNA Predict Ex Vivo Viral Outgrowth.

    Directory of Open Access Journals (Sweden)

    Maja Kiselinova

    2016-03-01

    Full Text Available The persistence of a reservoir of latently infected CD4 T cells remains one of the major obstacles to cure HIV. Numerous strategies are being explored to eliminate this reservoir. To translate these efforts into clinical trials, there is a strong need for validated biomarkers that can monitor the reservoir over time in vivo. A comprehensive study was designed to evaluate and compare potential HIV-1 reservoir biomarkers. A cohort of 25 patients, treated with suppressive antiretroviral therapy was sampled at three time points, with median of 2.5 years (IQR: 2.4-2.6 between time point 1 and 2; and median of 31 days (IQR: 28-36 between time point 2 and 3. Patients were median of 6 years (IQR: 3-12 on ART, and plasma viral load (<50 copies/ml was suppressed for median of 4 years (IQR: 2-8. Total HIV-1 DNA, unspliced (us and multiply spliced HIV-1 RNA, and 2LTR circles were quantified by digital PCR in peripheral blood, at 3 time points. At the second time point, a viral outgrowth assay (VOA was performed, and integrated HIV-1 DNA and relative mRNA expression levels of HIV-1 restriction factors were quantified. No significant change was found for long- and short-term dynamics of all HIV-1 markers tested in peripheral blood. Integrated HIV-1 DNA was associated with total HIV-1 DNA (p<0.001, R² = 0.85, us HIV-1 RNA (p = 0.029, R² = 0.40, and VOA (p = 0.041, R2 = 0.44. Replication-competent virus was detected in 80% of patients by the VOA and it correlated with total HIV-1 DNA (p = 0.039, R² = 0.54. The mean quantification difference between Alu-PCR and VOA was 2.88 log10, and 2.23 log10 between total HIV-1 DNA and VOA. The levels of usHIV-1 RNA were inversely correlated with mRNA levels of several HIV-1 restriction factors (TRIM5α, SAMHD1, MX2, SLFN11, pSIP1. Our study reveals important correlations between the viral outgrowth and total and integrated HIV-1 DNA measures, suggesting that the total pool of HIV-1 DNA may predict the size of the

  15. HIV-1 Tat regulates the expression of the dcw operon and stimulates the proliferation of bacteria.

    Science.gov (United States)

    Wei, Jinsong; Zhang, Yumin; Knapp, Pamela E; Zhao, Tianyong

    2016-01-01

    Infections of pathogenic bacteria are very common in acquired immunodeficiency syndrome (AIDS) patients. However, the biological effects of HIV-1 Tat on bacteria are incompletely understood. In this study, HIV-1 Tat was expressed in Escherichia coli and Pseudomonas aeruginosa (PA01) to investigate its biological effects on bacteria. Bacterial cells expressing either HIV-1 Tat1-86 (Tat1-86) or HIV-1 Tat1-72 (Tat1-72) grow significantly faster than those with either only an empty vector or an unrelated control (GFP or Rluc). Supplementation of purified HIV-1 Tat1-86 or Tat1-101 protein into bacterial culture medium stimulated the growth of both E. coli and PA01. The expression profile of certain cell division-associated genes, such as those in the division cell wall (dcw) operon (ftsA, ftsQ, ftsW and ftsZ), yafO and zipA, was altered in HIV-1 Tat1-86 expressing E. coli BL21(DE3). Furthermore, the expression of firefly luciferase (Fluc) reporter gene, when engineered for control by the dcw promoter and terminator, was enhanced by HIV-1 Tat in E. coli, confirming that HIV-1 Tat transcriptionally regulates the expression of the dcw operon. The finding that HIV-1 Tat stimulates bacterial growth whether it is produced intracellularly or applied extracellularly may have relevance for HIV patients who are highly susceptible to opportunistic bacterial infections. Contents category: Viruses -Retroviruses. The GenBank accession number for the sequence of HIV-1 Tat1-86 is AF324439.1. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Increasing procaspase 8 expression using repurposed drugs to induce HIV infected cell death in ex vivo patient cells.

    Directory of Open Access Journals (Sweden)

    Rahul Sampath

    Full Text Available HIV persists because a reservoir of latently infected CD4 T cells do not express viral proteins and are indistinguishable from uninfected cells. One approach to HIV cure suggests that reactivating HIV will activate cytotoxic pathways; yet when tested in vivo, reactivating cells do not die sufficiently to reduce cell-associated HIV DNA levels. We recently showed that following reactivation from latency, HIV infected cells generate the HIV specific cytotoxic protein Casp8p41 which is produced by HIV protease cleaving procaspase 8. However, cell death is prevented, possibly due to low procaspase 8 expression. Here, we tested whether increasing procaspase 8 levels in CD4 T cells will produce more Casp8p41 following HIV reactivation, causing more reactivated cells to die. Screening 1277 FDA approved drugs identified 168 that increased procaspase 8 expression by at least 1.7-fold. Of these 30 were tested for anti-HIV effects in an acute HIVIIIb infection model, and 9 drugs at physiologic relevant levels significantly reduced cell-associated HIV DNA. Primary CD4 T cells from ART suppressed HIV patients were treated with one of these 9 drugs and reactivated with αCD3/αCD28. Four drugs significantly increased Casp8p41 levels following HIV reactivation, and decreased total cell associated HIV DNA levels (flurbiprofen: p = 0.014; doxycycline: p = 0.044; indomethacin: p = 0.025; bezafibrate: P = 0.018 without effecting the viability of uninfected cells. Thus procaspase 8 levels can be increased pharmacologically and, in the context of HIV reactivation, increase Casp8p41 causing death of reactivating cells and decreased HIV DNA levels. Future studies will be required to define the clinical utility of this or similar approaches.

  17. Differential expression and interaction of host factors augment HIV-1 gene expression in neonatal mononuclear cells

    International Nuclear Information System (INIS)

    Sundaravaradan, Vasudha; Mehta, Roshni; Harris, David T.; Zack, Jerome A.; Ahmad, Nafees

    2010-01-01

    We have previously shown a higher level of HIV-1 replication and gene expression in neonatal (cord) blood mononuclear cells (CBMC) compared with adult blood cells (PBMC), which could be due to differential expression of host factors. We performed the gene expression profile of CBMC and PBMC and found that 8013 genes were expressed at higher levels in CBMC than PBMC and 8028 genes in PBMC than CBMC, including 1181 and 1414 genes upregulated after HIV-1 infection in CBMC and PBMC, respectively. Several transcription factors (NF-κB, E2F, HAT-1, TFIIE, Cdk9, Cyclin T1), signal transducers (STAT3, STAT5A) and cytokines (IL-1β, IL-6, IL-10) were upregulated in CBMC than PBMC, which are known to influence HIV-1 replication. In addition, a repressor of HIV-1 transcription, YY1, was down regulated in CBMC than PBMC and several matrix metalloproteinase (MMP-7, -12, -14) were significantly upregulated in HIV-1 infected CBMC than PBMC. Furthermore, we show that CBMC nuclear extracts interacted with a higher extent to HIV-1 LTR cis-acting sequences, including NF-κB, NFAT, AP1 and NF-IL6 compared with PBMC nuclear extracts and retroviral based short hairpin RNA (shRNA) for STAT3 and IL-6 down regulated their own and HIV-1 gene expression, signifying that these factors influenced differential HIV-1 gene expression in CBMC than PBMC.

  18. How Do Social Capital and HIV/AIDS Outcomes Geographically Cluster and Which Sociocontextual Mechanisms Predict Differences Across Clusters?

    Science.gov (United States)

    Ransome, Yusuf; Dean, Lorraine T; Crawford, Natalie D; Metzger, David S; Blank, Michael B; Nunn, Amy S

    2017-09-01

    Place of residence has been associated with HIV transmission risks. Social capital, defined as features of social organization that improve efficiency of society by facilitating coordinated actions, often varies by neighborhood, and hypothesized to have protective effects on HIV care continuum outcomes. We examined whether the association between social capital and 2 HIV care continuum outcomes clustered geographically and whether sociocontextual mechanisms predict differences across clusters. Bivariate Local Moran's I evaluated geographical clustering in the association between social capital (participation in civic and social organizations, 2006, 2008, 2010) and [5-year (2007-2011) prevalence of late HIV diagnosis and linkage to HIV care] across Philadelphia, PA, census tracts (N = 378). Maps documented the clusters and multinomial regression assessed which sociocontextual mechanisms (eg, racial composition) predict differences across clusters. We identified 4 significant clusters (high social capital-high HIV/AIDS, low social capital-low HIV/AIDS, low social capital-high HIV/AIDS, and high social capital-low HIV/AIDS). Moran's I between social capital and late HIV diagnosis was (I = 0.19, z = 9.54, P social capital was lowest and HIV burden the highest, compared with clusters with high social capital and lowest HIV burden. The association between social participation and HIV care continuum outcomes cluster geographically in Philadelphia, PA. HIV prevention interventions should account for this phenomenon. Reducing geographic disparities will require interventions tailored to each continuum step and that address socioeconomic factors such as neighborhood median income.

  19. Intragenic HIV-1 env sequences that enhance gag expression

    International Nuclear Information System (INIS)

    Suptawiwat, Ornpreya; Sutthent, Ruengpung; Lee, T.-H.; Auewarakul, Prasert

    2003-01-01

    Expression of HIV-1 genes is regulated at multiple levels including the complex RNA splicing and transport mechanisms. Multiple cis-acting elements involved in these regulations have been previously identified in various regions of HIV-1 genome. Here we show that another cis-acting element was present in HIV-1 env region. This element enhanced the expression of Gag when inserted together with Rev response element (RRE) into a truncated HIV-1 genome in the presence of Rev. The enhancing activity was mapped to a 263-bp fragment in the gp41 region downstream to RRE. RNA analysis showed that it might function by promoting RNA stability and Rev-dependent RNA export. The enhancement was specific to Rev-dependent expression, since it did not enhance Gag expression driven by Sam68, a cellular protein that has been shown to be able to substitute for Rev in RNA export function

  20. Association of a 3' untranslated region polymorphism in proprotein convertase subtilisin/kexin type 9 with HIV viral load and CD4+ levels in HIV/hepatitis C virus coinfected women.

    Science.gov (United States)

    Kuniholm, Mark H; Liang, Hua; Anastos, Kathryn; Gustafson, Deborah; Kassaye, Seble; Nowicki, Marek; Sha, Beverly E; Pawlowski, Emilia J; Gange, Stephen J; Aouizerat, Bradley E; Pushkarsky, Tatiana; Bukrinsky, Michael I; Prasad, Vinayaka R

    2017-11-28

    To assess variation in genes that regulate cholesterol metabolism in relation to the natural history of HIV infection. Cross-sectional and longitudinal analysis of the Women's Interagency HIV Study. We examined 2050 single nucleotide polymorphisms (SNPs) in 19 genes known to regulate cholesterol metabolism in relation to HIV viral load and CD4 T-cell levels in a multiracial cohort of 1066 antiretroviral therapy-naive women. Six SNPs were associated with both HIV viral load and CD4 T-cell levels at a false discovery rate of 0.01. Bioinformatics tools did not predict functional activity for five SNPs, located in introns of nuclear receptor corepressor 2, retinoid X receptor alpha (RXRA), and tetratricopeptide repeat domain 39B. Rs17111557 located in the 3' untranslated region of proprotein convertase subtilisin/kexin type 9 (PCSK9) putatively affects binding of hsa-miR-548t-5p and hsa-miR-4796-3p, which could regulate PCSK9 expression levels. Interrogation of rs17111557 revealed stronger associations in the subset of women with HIV/hepatitis C virus (HCV) coinfection (n = 408, 38% of women). Rs17111557 was also associated with low-density lipoprotein cholesterol levels in HIV/HCV coinfected (β: -10.4; 95% confidence interval: -17.9, -2.9; P = 0.007), but not in HIV monoinfected (β:1.2; 95% confidence interval: -6.3, 8.6; P = 0.76) women in adjusted analysis. PCSK9 polymorphism may affect HIV pathogenesis, particularly in HIV/HCV coinfected women. A likely mechanism for this effect is PCSK9-mediated regulation of cholesterol metabolism. Replication in independent cohorts is needed to clarify the generalizability of the observed associations.

  1. Genital herpes simplex virus type 2 infection in humanized HIV-transgenic mice triggers HIV shedding and is associated with greater neurological disease.

    Science.gov (United States)

    Nixon, Briana; Fakioglu, Esra; Stefanidou, Martha; Wang, Yanhua; Dutta, Monica; Goldstein, Harris; Herold, Betsy C

    2014-02-15

    Epidemiological studies consistently demonstrate synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1). Higher HIV-1 loads are observed in coinfected individuals, and conversely, HIV-1 is associated with more-severe herpetic disease. A small animal model of coinfection would facilitate identification of the biological mechanisms underlying this synergy and provide the opportunity to evaluate interventions. Mice transgenic for HIV-1 provirus and human cyclin T1 under the control of a CD4 promoter (JR-CSF/hu-cycT1) were intravaginally infected with HSV-2 and evaluated for disease progression, HIV shedding, and mucosal immune responses. HSV-2 infection resulted in higher vaginal HIV loads and genital tissue expression of HIV RNA, compared with HSV-uninfected JR-CSF/hu-cycT1 mice. There was an increase in genital tract inflammatory cells, cytokines, chemokines, and interferons in response to HSV-2, although the kinetics of the response were delayed in HIV-transgenic, compared with control mice. Moreover, the JR-CSF/hu-cycT1 mice exhibited earlier and more-severe neurological disease. The latter was associated with downregulation of secretory leukocyte protease inhibitor expression in neuronal tissue, a molecule with antiinflammatory, antiviral, and neuroprotective properties. JR-CSF/hu-cycT1 mice provide a valuable model to study HIV/HSV-2 coinfection and identify potential mechanisms by which HSV-2 facilitates HIV-1 transmission and HIV modulates HSV-2-mediated disease.

  2. An association between neighbourhood wealth inequality and HIV prevalence in sub-Saharan Africa.

    Science.gov (United States)

    Brodish, Paul Henry

    2015-05-01

    This paper investigates whether community-level wealth inequality predicts HIV serostatus using DHS household survey and HIV biomarker data for men and women ages 15-59 pooled from six sub-Saharan African countries with HIV prevalence rates exceeding 5%. The analysis relates the binary dependent variable HIV-positive serostatus and two weighted aggregate predictors generated from the DHS Wealth Index: the Gini coefficient, and the ratio of the wealth of households in the top 20% wealth quintile to that of those in the bottom 20%. In separate multilevel logistic regression models, wealth inequality is used to predict HIV prevalence within each statistical enumeration area, controlling for known individual-level demographic predictors of HIV serostatus. Potential individual-level sexual behaviour mediating variables are added to assess attenuation, and ordered logit models investigate whether the effect is mediated through extramarital sexual partnerships. Both the cluster-level wealth Gini coefficient and wealth ratio significantly predict positive HIV serostatus: a 1 point increase in the cluster-level Gini coefficient and in the cluster-level wealth ratio is associated with a 2.35 and 1.3 times increased likelihood of being HIV positive, respectively, controlling for individual-level demographic predictors, and associations are stronger in models including only males. Adding sexual behaviour variables attenuates the effects of both inequality measures. Reporting eleven plus lifetime sexual partners increases the odds of being HIV positive over five-fold. The likelihood of having more extramarital partners is significantly higher in clusters with greater wealth inequality measured by the wealth ratio. Disaggregating logit models by sex indicates important risk behaviour differences. Household wealth inequality within DHS clusters predicts HIV serostatus, and the relationship is partially mediated by more extramarital partners. These results emphasize the importance

  3. Finding Relational Associations in HIV Resistance Mutation Data

    Science.gov (United States)

    Richter, Lothar; Augustin, Regina; Kramer, Stefan

    HIV therapy optimization is a hard task due to rapidly evolving mutations leading to drug resistance. Over the past five years, several machine learning approaches have been developed for decision support, mostly to predict therapy failure from the genotypic sequence of viral proteins and additional factors. In this paper, we define a relational representation for an important part of the data, namely the sequences of a viral protein (reverse transcriptase), their mutations, and the drug resistance(s) associated with those mutations. The data were retrieved from the Los Alamos National Laboratories' (LANL) HIV databases. In contrast to existing work in this area, we do not aim directly for predictive modeling, but take one step back and apply descriptive mining methods to develop a better understanding of the correlations and associations between mutations and resistances. In our particular application, we use the Warmr algorithm to detect non-trivial patterns connecting mutations and resistances. Our findings suggest that well-known facts can be rediscovered, but also hint at the potential of discovering yet unknown associations.

  4. HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

    Science.gov (United States)

    Richardson, Simone I; Chung, Amy W; Natarajan, Harini; Mabvakure, Batsirai; Mkhize, Nonhlanhla N; Garrett, Nigel; Abdool Karim, Salim; Moore, Penny L; Ackerman, Margaret E; Alter, Galit; Morris, Lynn

    2018-04-01

    While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

  5. Factors associated with abnormal spirometry among HIV-infected individuals.

    Science.gov (United States)

    Drummond, M Bradley; Huang, Laurence; Diaz, Philip T; Kirk, Gregory D; Kleerup, Eric C; Morris, Alison; Rom, William; Weiden, Michael D; Zhao, Enxu; Thompson, Bruce; Crothers, Kristina

    2015-08-24

    HIV-infected individuals are susceptible to development of chronic lung diseases, but little is known regarding the prevalence and risk factors associated with different spirometric abnormalities in this population. We sought to determine the prevalence, risk factors and performance characteristics of risk factors for spirometric abnormalities among HIV-infected individuals. Cross-sectional cohort study. We analyzed cross-sectional US data from the NHLBI-funded Lung-HIV consortium - a multicenter observational study of heterogeneous groups of HIV-infected participants in diverse geographic sites. Logistic regression analysis was performed to determine factors statistically significantly associated with spirometry patterns. A total of 908 HIV-infected individuals were included. The median age of the cohort was 50 years, 78% were men and 68% current smokers. An abnormal spirometry pattern was present in 37% of the cohort: 27% had obstructed and 10% had restricted spirometry patterns. Overall, age, smoking status and intensity, history of Pneumocystis infection, asthma diagnosis and presence of respiratory symptoms were independently associated with an abnormal spirometry pattern. Regardless of the presence of respiratory symptoms, five HIV-infected participants would need to be screened with spirometry to diagnose two individuals with any abnormal spirometry pattern. Nearly 40% of a diverse US cohort of HIV-infected individuals had an abnormal spirometry pattern. Specific characteristics including age, smoking status, respiratory infection history and respiratory symptoms can identify those at risk for abnormal spirometry. The high prevalence of abnormal spirometry and the poor predictive capability of respiratory symptoms to identify abnormal spirometry should prompt clinicians to consider screening spirometry in HIV-infected populations.

  6. MLH1 expression predicts the response to preoperative therapy and is associated with PD-L1 expression in esophageal cancer.

    Science.gov (United States)

    Momose, Kota; Yamasaki, Makoto; Tanaka, Koji; Miyazaki, Yasuhiro; Makino, Tomoki; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

    2017-07-01

    Programmed death-ligand 1 (PD-1/PD-L1) inhibition therapy demonstrates potential as a future treatment for esophageal cancer. Mismatch repair status and tumor PD-L1 expression are the candidate predictive biomarkers for response to this therapy. In colorectal cancer, mismatch repair-deficient tumors are associated with improved survival, although they are not sensitive to 5-fluorouracil-based chemotherapy. The purpose of the present study was to investigate the association between MutL homolog 1 (MLH1) expression and prognosis, response to therapy and PD-L1 expression in esophageal cancer. Immunohistochemistry was used to evaluate MLH1 and PD-L1 expression in 251 resected specimens. Of the specimens, 30.3% exhibited low MLH1 expression and 15.5% exhibited high PD-L1 expression. The 5-year overall survival rates for the high MLH1 expression group and the low MLH1 expression group were 51.3 and 55.6%, respectively (P=0.5260). The responder ratio was 45.7% in the high MLH1 expression group and 15.4% in the low MLH1 expression group (PMLH1 expression group (P=0.0064) and 25.0% in the low MLH1 expression group. MLH1 expression may be a predictive factor for the response to preoperative therapy in esophageal cancer, and esophageal cancer with low MLH1 expression may have a mechanism that assists in promoting tumor PD-L1 expression.

  7. Gene Expression Profiles of HIV/AIDS Patients with Qi-Yin Deficiency and Dampness-Heat Retention.

    Science.gov (United States)

    Liu, Sa; Chen, Yulong; Xie, Shiping; Xu, Qianlei; Chen, Jianshe; Wang, Changhai; Wang, Zhao; Ma, Suna; Wu, Xingwei; Zhang, Ning

    2016-11-01

    Traditional Chinese Medicine (TCM) applied in the clinic as a complementary and alternative therapy has helped improve immunity and reduce side effects and symptomatic treatment in patients with HIV/AIDS. However, the mechanisms of TCM syndromes are not clear. Transcriptomics enables the study of such TCM syndromes. This study compared the messenger RNA (mRNA) expressions of healthy persons and patients with HIV/AIDS who had two common TCM syndromes, qi-yin deficiency and dampness-heat retention, to find the difference in HIV/AIDS with TCM syndromes. Comparison with healthy persons identified 113 mRNAs-41 enhanced and 72 decreased-in the qi-yin deficiency group. Additionally, 76 mRNAs were found in the dampness-heat retention group: 14 increased and 62 decreased. Functional genetic analysis of the mRNAs indicated that two TCM syndromes were correlated with cell apoptosis, immunoinflammatory responses, and lymphocyte activation. Differentially expressed mRNAs in the qi-yin deficiency group were obviously associated with cellular activity, communication, protein localization, cellular ion homeostasis, and regulation of cell motion, whereas mRNAs in the dampness-heat retention group were associated with sequence-specific DNA binding, cellular response to stress, and hemopoietic or lymphoid organ development. These results suggest that the formation of different TCM syndromes in patients with HIV/AIDS were founded on biological transcriptomics, which reveal mechanisms of the formation of these syndromes in HIV/AIDS. Differentially expressed mRNAs in two TCM syndrome groups tended to normalize after TCM intervention, which indicates that TCM might remit symptoms by changing genetic expression.

  8. Lipoprotein(a) and HIV: Allele-Specific Apolipoprotein(a) Levels Predict Carotid Intima-Media Thickness in HIV-Infected Young Women in the Women's Interagency HIV Study.

    Science.gov (United States)

    Enkhmaa, Byambaa; Anuurad, Erdembileg; Zhang, Wei; Li, Chin-Shang; Kaplan, Robert; Lazar, Jason; Merenstein, Dan; Karim, Roksana; Aouizerat, Brad; Cohen, Mardge; Butler, Kenneth; Pahwa, Savita; Ofotokun, Igho; Adimora, Adaora A; Golub, Elizabeth; Berglund, Lars

    2017-05-01

    In the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)-related elevated cardiovascular disease risk remain unclear. The associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima-media thickness were assessed in 150 HIV-infected and 100 HIV-uninfected women in the WIHS (Women's Interagency HIV Study). Linear regression analyses with and without adjustments were used. The cohort was young (mean age, ≈31 years), with the majority being Blacks (≈70%). The prevalence of a small size apo(a) (≤22 Kringle repeats) or a high Lp(a) level (≥30 mg/dL) was similar by HIV status. Total plasma Lp(a) level ( P =0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes ( P =0.022) were significantly associated with carotid artery intima-media thickness in the HIV-infected women only. After accounting for confounders (age, race, smoking, body mass index, blood pressure, hepatitis C virus coinfection, menopause, plasma lipids, treatment status, CD4 + T cell count, and HIV/RNA viral load), the association remained significant for both Lp(a) ( P =0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes ( P =0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with carotid artery intima-media thickness. Lp(a) and allele-specific apo(a) levels predict carotid artery intima-media thickness in HIV-infected young women. Further research is needed to identify underlying mechanisms of an increased Lp(a) atherogenicity in HIV infection. © 2017 American Heart Association, Inc.

  9. HIV-associated lung cancer: survival in an unselected cohort.

    Science.gov (United States)

    Hoffmann, Christian; Kohrs, Fabienne; Sabranski, Michael; Wolf, Eva; Jaeger, Hans; Wyen, Christoph; Siehl, Jan; Baumgarten, Axel; Hensel, Manfred; Jessen, Arne; Schaaf, Bernhard; Vogel, Martin; Bogner, Johannes; Horst, Heinz-August; Stephan, Christoph

    2013-10-01

    Lung cancer is one of the most common non-AIDS-defining malignancies in HIV-infected patients. However, data on clinical outcome and prognostic factors are scarce. This was a national German multicentre, retrospective cohort analysis of all cases of lung cancer seen in HIV-infected individuals from 2000 through 2010. Survival was analyzed with respect to the use of antiretroviral therapy (ART), specific lung cancer therapies, and other potential prognostic factors. A total of 72 patients (mean age 55.5 y, CD4 T-cells 383/μl) were evaluated in this analysis. At time of lung cancer diagnosis, 86% were on ART. Of these, 79% had undetectable HIV-1 RNA (cancer stage of I-IIIA was associated with better overall survival when compared with the advanced stages IIIb/IV (p = 0.0003). Other factors predictive of improved overall survival were better performance status, CD4 T-cells > 200/μl, and a non-intravenous drug use transmission risk for HIV. Currently, most cases of lung cancer occur in the setting of limited immune deficiency and a long-lasting viral suppression. As in HIV-negative cases, the clinical stage of lung cancer is highly predictive of survival, and long-term overall survival can only be achieved at the limited stages. The still high mortality underscores the importance of smoking cessation strategies in HIV-infected patients.

  10. Methamphetamine and HIV-Tat alter murine cardiac DNA methylation and gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Koczor, Christopher A., E-mail: ckoczor@emory.edu; Fields, Earl; Jedrzejczak, Mark J.; Jiao, Zhe; Ludaway, Tomika; Russ, Rodney; Shang, Joan; Torres, Rebecca A.; Lewis, William

    2015-11-01

    This study addresses the individual and combined effects of HIV-1 and methamphetamine (N-methyl-1-phenylpropan-2-amine, METH) on cardiac dysfunction in a transgenic mouse model of HIV/AIDS. METH is abused epidemically and is frequently associated with acquisition of HIV-1 infection or AIDS. We employed microarrays to identify mRNA differences in cardiac left ventricle (LV) gene expression following METH administration (10 d, 3 mg/kg/d, subcutaneously) in C57Bl/6 wild-type littermates (WT) and Tat-expressing transgenic (TG) mice. Arrays identified 880 differentially expressed genes (expression fold change > 1.5, p < 0.05) following METH exposure, Tat expression, or both. Using pathway enrichment analysis, mRNAs encoding polypeptides for calcium signaling and contractility were altered in the LV samples. Correlative DNA methylation analysis revealed significant LV DNA methylation changes following METH exposure and Tat expression. By combining these data sets, 38 gene promoters (27 related to METH, 11 related to Tat) exhibited differences by both methods of analysis. Among those, only the promoter for CACNA1C that encodes L-type calcium channel Cav1.2 displayed DNA methylation changes concordant with its gene expression change. Quantitative PCR verified that Cav1.2 LV mRNA abundance doubled following METH. Correlative immunoblots specific for Cav1.2 revealed a 3.5-fold increase in protein abundance in METH LVs. Data implicate Cav1.2 in calcium dysregulation and hypercontractility in the murine LV exposed to METH. They suggest a pathogenetic role for METH exposure to promote LV dysfunction that outweighs Tat-induced effects. - Highlights: • HIV-1 Tat and methamphetamine (METH) alter cardiac gene expression and epigenetics. • METH impacts gene expression or epigenetics more significantly than Tat expression. • METH alters cardiac mitochondrial function and calcium signaling independent of Tat. • METH alters DNA methylation, expression, and protein abundance of

  11. Methamphetamine and HIV-Tat alter murine cardiac DNA methylation and gene expression

    International Nuclear Information System (INIS)

    Koczor, Christopher A.; Fields, Earl; Jedrzejczak, Mark J.; Jiao, Zhe; Ludaway, Tomika; Russ, Rodney; Shang, Joan; Torres, Rebecca A.; Lewis, William

    2015-01-01

    This study addresses the individual and combined effects of HIV-1 and methamphetamine (N-methyl-1-phenylpropan-2-amine, METH) on cardiac dysfunction in a transgenic mouse model of HIV/AIDS. METH is abused epidemically and is frequently associated with acquisition of HIV-1 infection or AIDS. We employed microarrays to identify mRNA differences in cardiac left ventricle (LV) gene expression following METH administration (10 d, 3 mg/kg/d, subcutaneously) in C57Bl/6 wild-type littermates (WT) and Tat-expressing transgenic (TG) mice. Arrays identified 880 differentially expressed genes (expression fold change > 1.5, p < 0.05) following METH exposure, Tat expression, or both. Using pathway enrichment analysis, mRNAs encoding polypeptides for calcium signaling and contractility were altered in the LV samples. Correlative DNA methylation analysis revealed significant LV DNA methylation changes following METH exposure and Tat expression. By combining these data sets, 38 gene promoters (27 related to METH, 11 related to Tat) exhibited differences by both methods of analysis. Among those, only the promoter for CACNA1C that encodes L-type calcium channel Cav1.2 displayed DNA methylation changes concordant with its gene expression change. Quantitative PCR verified that Cav1.2 LV mRNA abundance doubled following METH. Correlative immunoblots specific for Cav1.2 revealed a 3.5-fold increase in protein abundance in METH LVs. Data implicate Cav1.2 in calcium dysregulation and hypercontractility in the murine LV exposed to METH. They suggest a pathogenetic role for METH exposure to promote LV dysfunction that outweighs Tat-induced effects. - Highlights: • HIV-1 Tat and methamphetamine (METH) alter cardiac gene expression and epigenetics. • METH impacts gene expression or epigenetics more significantly than Tat expression. • METH alters cardiac mitochondrial function and calcium signaling independent of Tat. • METH alters DNA methylation, expression, and protein abundance of

  12. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark.

    Science.gov (United States)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S; Storgaard, Merete; Rönsholt, Frederikke F; Johansen, Isik S; Pedersen, Gitte; Nørregård Nielsen, Lars; Bonde, Jesper; Katzenstein, Terese L; Weis, Nina; Lebech, Anne-Mette

    2017-05-31

    Bacterial vaginosis (BV) has been found to be associated with HIV acquisition and transmission. This is suggested to be due to higher HIV RNA levels in cervicovaginal fluids in women living with HIV (WLWH) with BV, as bacteria associated with BV may induce viral replication and shedding in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. WLWH between 18-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes viridae, and vaginal HIV viral load. Median age of the 150 included women was 41 years; ethnicity was predominantly White (35%) or Black (47%). The majority (96%) was on ART and had undetectable (85%) plasma HIV RNA (<40 copies/mL). BV was diagnosed in 32%. Overall, 11% had detectable vaginal HIV RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies that HIV shedding does not seem to be increased by BV.

  13. Factors Associated with Recent HIV Testing among Heterosexuals at High-Risk for HIV Infection in New York City

    Directory of Open Access Journals (Sweden)

    Marya eGwadz

    2016-04-01

    Full Text Available Background. The CDC recommends persons at high-risk for HIV infection in the United States receive annual HIV testing to foster early HIV diagnosis and timely linkage to health care. Heterosexuals make up a significant proportion of incident HIV infections (>25%, but test for HIV less frequently than those in other risk categories. Yet factors that promote or impede annual HIV testing among heterosexuals are poorly understood. The present study examines individual/attitudinal-, social-, and structural-level factors associated with past-year HIV testing among heterosexuals at high-risk for HIV. Methods. Participants were African American/Black and Hispanic heterosexual adults (N=2307 residing in an urban area with both high poverty and HIV prevalence rates. Participants were recruited by respondent-driven sampling (RDS in 2012-2015 and completed a computerized structured assessment battery covering background factors, multi-level putative facilitators of HIV testing, and HIV testing history. Separate logistic regression analysis for males and females identified factors associated with past-year HIV testing.Results. Participants were mostly male (58%, African American/Black (75%, and 39 years old on average (SD = 12.06 years. Lifetime homelessness (54% and incarceration (62% were common. Half reported past-year HIV testing (50% and 37% engaged in regular, annual HIV testing. Facilitators of HIV testing common to both genders included sexually transmitted infection (STI testing or STI diagnosis, peer norms supporting HIV testing, and HIV testing access. Among women, access to general medical care and extreme poverty further predicted HIV testing, while recent drug use reduced the odds of past-year HIV testing. Among men, past-year HIV testing was also associated with lifetime incarceration and substance use treatment.Conclusions. The present study identified gaps in rates of HIV testing among heterosexuals at high-risk for HIV, and both common and

  14. Facial Emotion Recognition Impairments are Associated with Brain Volume Abnormalities in Individuals with HIV

    Science.gov (United States)

    Clark, Uraina S.; Walker, Keenan A.; Cohen, Ronald A.; Devlin, Kathryn N.; Folkers, Anna M.; Pina, Mathew M.; Tashima, Karen T.

    2015-01-01

    Impaired facial emotion recognition abilities in HIV+ patients are well documented, but little is known about the neural etiology of these difficulties. We examined the relation of facial emotion recognition abilities to regional brain volumes in 44 HIV-positive (HIV+) and 44 HIV-negative control (HC) adults. Volumes of structures implicated in HIV− associated neuropathology and emotion recognition were measured on MRI using an automated segmentation tool. Relative to HC, HIV+ patients demonstrated emotion recognition impairments for fearful expressions, reduced anterior cingulate cortex (ACC) volumes, and increased amygdala volumes. In the HIV+ group, fear recognition impairments correlated significantly with ACC, but not amygdala volumes. ACC reductions were also associated with lower nadir CD4 levels (i.e., greater HIV-disease severity). These findings extend our understanding of the neurobiological substrates underlying an essential social function, facial emotion recognition, in HIV+ individuals and implicate HIV-related ACC atrophy in the impairment of these abilities. PMID:25744868

  15. HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Simone I Richardson

    2018-04-01

    Full Text Available While the induction of broadly neutralizing antibodies (bNAbs is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP, complement deposition (ADCD, cellular cytotoxicity (ADCC and cellular trogocytosis (ADCT were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

  16. The National NeuroAIDS Tissue Consortium brain gene array: two types of HIV-associated neurocognitive impairment.

    Directory of Open Access Journals (Sweden)

    Benjamin B Gelman

    Full Text Available The National NeuroAIDS Tissue Consortium (NNTC performed a brain gene expression array to elucidate pathophysiologies of Human Immunodeficiency Virus type 1 (HIV-1-associated neurocognitive disorders.Twenty-four human subjects in four groups were examined A Uninfected controls; B HIV-1 infected subjects with no substantial neurocognitive impairment (NCI; C Infected with substantial NCI without HIV encephalitis (HIVE; D Infected with substantial NCI and HIVE. RNA from neocortex, white matter, and neostriatum was processed with the Affymetrix® array platform.With HIVE the HIV-1 RNA load in brain tissue was three log(10 units higher than other groups and over 1,900 gene probes were regulated. Interferon response genes (IFRGs, antigen presentation, complement components and CD163 antigen were strongly upregulated. In frontal neocortex downregulated neuronal pathways strongly dominated in HIVE, including GABA receptors, glutamate signaling, synaptic potentiation, axon guidance, clathrin-mediated endocytosis and 14-3-3 protein. Expression was completely different in neuropsychologically impaired subjects without HIVE. They had low brain HIV-1 loads, weak brain immune responses, lacked neuronally expressed changes in neocortex and exhibited upregulation of endothelial cell type transcripts. HIV-1-infected subjects with normal neuropsychological test results had upregulation of neuronal transcripts involved in synaptic transmission of neostriatal circuits.Two patterns of brain gene expression suggest that more than one pathophysiological process occurs in HIV-1-associated neurocognitive impairment. Expression in HIVE suggests that lowering brain HIV-1 replication might improve NCI, whereas NCI without HIVE may not respond in kind; array results suggest that modulation of transvascular signaling is a potentially promising approach. Striking brain regional differences highlighted the likely importance of circuit level disturbances in HIV/AIDS. In

  17. Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lipodystrophy syndrome.

    Directory of Open Access Journals (Sweden)

    Pere Domingo

    Full Text Available BACKGROUND: Uridine has been advocated for the treatment of HIV-1/HAART-associated lipodystrophy (HALS, although its metabolism in HIV-1-infected patients is poorly understood. METHODS: Plasma uridine concentrations were measured in 35 controls and 221 HIV-1-infected patients and fat uridine in 15 controls and 19 patients. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Uridine was measured by a binary gradient-elution HPLC method. Analysis of genes encoding uridine metabolizing enzymes in fat was performed with TaqMan RT-PCR. RESULTS: Median plasma uridine concentrations for HIV-1-infected patients were 3.80 µmol/l (interquartile range: 1.60, and for controls 4.60 µmol/l (IQR: 1.8 (P = 0.0009. In fat, they were of 6.0 (3.67, and 2.8 (4.65 nmol/mg of protein, respectively (P = 0.0118. Patients with a mixed HALS form had a median plasma uridine level of 4.0 (IC95%: 3.40-4.80 whereas in those with isolated lipoatrophy it was 3.25 (2.55-4.15 µmol/l/l (P = 0.0066. The expression of uridine cytidine kinase and uridine phosphorylase genes was significantly decreased in all groups of patients with respect to controls. A higher expression of the mRNAs for concentrative nucleoside transporters was found in HIV-1-infected patients with respect to healthy controls. CONCLUSIONS: HIV-1 infection is associated with a decrease in plasma uridine and a shift of uridine to the adipose tissue compartment. Antiretroviral therapy was not associated with plasma uridine concentrations, but pure lipoatrophic HALS was associated with significantly lower plasma uridine concentrations.

  18. HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers.

    Science.gov (United States)

    Pai, Sara I; Jack Lee, J; Carey, Thomas E; Westra, William H; Ferrone, Soldano; Moore, Charles; Mosunjac, Marina B; Shin, Dong M; Ferris, Robert L

    2018-02-01

    Human immunodeficiency virus (HIV)-infected individuals are at increased risk for developing several non-AIDS related malignancies and are often excluded from cancer immunotherapy regimens. To evaluate the immune competence of this cancer patient population, we evaluated HLA class I antigen presenting machinery (APM) component expression and PD-1:PD-L1 pathway upregulation in HIV(+) and HIV(-) head and neck cancers (HNCs). Sixty-two HIV(+) and 44 matched HIV(-) controls diagnosed with HNC between 1991 and 2011 from five tertiary care referral centers in the United States were identified. HLA class I APM component, PD-1, and PD-L1 expression were analyzed by immunohistochemical staining with monoclonal antibodies (mAbs). Clinical data was abstracted from the medical records. There was no significant difference between the cases and controls in LMP2, TAP1, HLA-A and HLA-B/C, as well as PD-1 and PD-L1 expression. Overall, 62% of all subjects had high PD-1 expression and 82% of the subjects expressed PD-L1 within the tumor microenvironment. LMP2, HLA-A and HLA-B/C expression were significantly associated with moderate to high PD-1 expression in the HIV(+) HNC cases (p = .004, p = .026, and p = .006, respectively) but not in the HIV(-) controls. In addition, HLA-A expression was significantly associated with PD-L1 expression in the HIV(+) HNC cases only (p = .029). HIV-infected individuals diagnosed with HNC do not have any detectable defects in HLA class I APM component expression and in PD-1:PD-L1 pathway activation. Given the current successes of HAART therapy in maintaining immune cell counts, HIV(+) patients diagnosed with cancer may benefit from the recently FDA-approved immune checkpoint blockade therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Predictive value of prostate specific antigen in a European HIV-positive cohort

    DEFF Research Database (Denmark)

    Shepherd, Leah; Borges, Álvaro H; Ravn, Lene

    2016-01-01

    BACKGROUND: It is common practice to use prostate specific antigen (PSA) ≥4.0 ng/ml as a clinical indicator for men at risk of prostate cancer (PCa), however, this is unverified in HIV+ men. We aimed to describe kinetics and predictive value of PSA for PCa in HIV+ men. METHODS: A nested case...... control study of 21 men with PCa and 40 matched-controls within EuroSIDA was conducted. Prospectively stored plasma samples before PCa (or matched date in controls) were measured for the following markers: total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG). Conditional...... logistic regression models investigated associations between markers and PCa. Mixed models were used to describe kinetics. Sensitivity and specificity of using tPSA >4 ng/ml to predict PCa was calculated. Receiver operating characteristic curves were used to identify optimal cutoffs in HIV+ men for total...

  20. Regional gene expression of LOX-1, VCAM-1, and ICAM-1 in aorta of HIV-1 transgenic rats.

    Directory of Open Access Journals (Sweden)

    Anne Mette Fisker Hag

    Full Text Available BACKGROUND: Increased prevalence of atherosclerotic cardiovascular disease in HIV-infected patients has been observed. The cause of this accelerated atherosclerosis is a matter of controversy. As clinical studies are complicated by a multiplicity of risk-factors and a low incidence of hard endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1, vascular cell adhesion molecule-1 (VCAM-1, and intercellular adhesion molecule-1 (ICAM-1 in HIV-1 transgenic (HIV-1Tg rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1 was elevated in the HIV-1Tg rats compared to controls, but the ICAM-1 gene expression profile did not show any differences between the groups. CONCLUSIONS/SIGNIFICANCE: HIV-1Tg rats have gene expression patterns indicating endothelial dysfunction and accelerated atherosclerosis in aorta, suggesting that HIV-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular disease.

  1. DJ1 Expression Downregulates in Neuroblastoma Cells (SK-N-MC Chronically Exposed to HIV-1 and Cocaine.

    Directory of Open Access Journals (Sweden)

    Upal eRoy

    2015-07-01

    Full Text Available Background: HIV-associated neurological disorder (HAND has long been recognized as a consequence of Human Immunodeficiency Virus (HIV infection in the brain. The pathology of HAND gets more complicated with the recreational drug use such as cocaine. Recent studies have suggested multiple genetic influences involved in the pathology of addiction and HAND but only a fraction of the entire genetic risk has been investigated so far. In this regard, role of DJ1 protein (a gene linked to autosomal recessive early-onset Parkinson’s disease in regulating dopamine transmission and reactive oxygen species (ROS production in neuronal cells will be worth investigating in HIV-1 and cocaine exposed microenvironment. Being a very abundant protein in the brain, DJ1 could serve as a potential marker for early detection of HIV-1 and/or cocaine related neurological disorder.Methods: In vitro analysis was done to observe the effect of HIV-1 and/or cocaine on DJ1 protein expression in neuroblastoma cells (SK-N-MC. Gene expression and protein analysis of DJ1 was done on the HIV infected and/or cocaine treated SK-N-MC and compared to untreated cells using real time PCR, Western Blot and flow cytometry.Results: Gene expression and protein analysis indicated that there was a significant decrease in DJ1 expression in SK-N-MC chronically exposed to HIV-1 and/or cocaine.Conclusion: This is the first study to establish that DJ1 expression level in the neuronal cells significantly decreased in presence of HIV-1and/or cocaine indicating oxidative stress level of dopamine neurons.

  2. Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control.

    Directory of Open Access Journals (Sweden)

    Adam R Hersperger

    2010-05-01

    Full Text Available Many immune correlates of CD8(+ T-cell-mediated control of HIV replication, including polyfunctionality, proliferative ability, and inhibitory receptor expression, have been discovered. However, no functional correlates using ex vivo cells have been identified with the known ability to cause the direct elimination of HIV-infected cells. We have recently discovered the ability of human CD8(+ T-cells to rapidly upregulate perforin--an essential molecule for cell-mediated cytotoxicity--following antigen-specific stimulation. Here, we examined perforin expression capability in a large cross-sectional cohort of chronically HIV-infected individuals with varying levels of viral load: elite controllers (n = 35, viremic controllers (n = 29, chronic progressors (n = 27, and viremic nonprogressors (n = 6. Using polychromatic flow cytometry and standard intracellular cytokine staining assays, we measured perforin upregulation, cytokine production, and degranulation following stimulation with overlapping peptide pools encompassing all proteins of HIV. We observed that HIV-specific CD8(+ T-cells from elite controllers consistently display an enhanced ability to express perforin directly ex vivo compared to all other groups. This ability is not restricted to protective HLA-B haplotypes, does not require proliferation or the addition of exogenous factors, is not restored by HAART, and primarily originates from effector CD8(+ T-cells with otherwise limited functional capability. Notably, we found an inverse relationship between HIV-specific perforin expression and viral load. Thus, the capability of HIV-specific CD8(+ T-cells to rapidly express perforin defines a novel correlate of control in HIV infection.

  3. CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients.

    Science.gov (United States)

    Avelino-Silva, Vivian I; Miyaji, Karina T; Hunt, Peter W; Huang, Yong; Simoes, Marisol; Lima, Sheila B; Freire, Marcos S; Caiaffa-Filho, Helio H; Hong, Marisa A; Costa, Dayane Alves; Dias, Juliana Zanatta C; Cerqueira, Natalia B; Nishiya, Anna Shoko; Sabino, Ester Cerdeira; Sartori, Ana M; Kallas, Esper G

    2016-12-01

    HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence vaccine response in this population. We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models. 12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers. HIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio.

  4. HIV- and AIDS-associated cancers.

    Science.gov (United States)

    Carr, Ellen R

    2013-04-01

    One of the most significant world epidemics in history, HIV/AIDS, has been a research priority since its discovery in 1981. This review article provides an update on HIV/AIDS, with a specific focus on the diagnosis and care of patients with HIV- and AIDS-associated cancers.

  5. HIV-associated anal cancer

    OpenAIRE

    Newsom-Davis, T; Bower, M

    2010-01-01

    HIV-associated anal carcinoma, a non-AIDS-defining cancer, is a human papillomavirus-associated malignancy with a spectrum of preinvasive changes. The standardized incidence ratio for anal cancer in patients with HIV/AIDS is 20-50. Algorithms for anal cancer screening include anal cytology followed by high-resolution anoscopy for those with abnormal findings. Outpatient topical treatments for anal intraepithelial neoplasia include infrared coagulation therapy, trichloroacetic acid, and imiqui...

  6. Does message framing predict willingness to participate in a hypothetical HIV vaccine trial: an application of Prospect Theory.

    Science.gov (United States)

    Evangeli, Michael; Kafaar, Zuhayr; Kagee, Ashraf; Swartz, Leslie; Bullemor-Day, Philippa

    2013-01-01

    It is vital that enough participants are willing to participate in clinical trials to test HIV vaccines adequately. It is, therefore, necessary to explore what affects peoples' willingness to participate (WTP) in such trials. Studies have only examined individual factors associated with WTP and not the effect of messages about trial participation on potential participants (e.g., whether losses or gains are emphasized, or whether the outcome is certain or uncertain). This study explores whether the effects of message framing on WTP in a hypothetical HIV vaccine trial are consistent with Prospect Theory. This theory suggests that people are fundamentally risk averse and that (1) under conditions of low risk and high certainty, gain-framed messages will be influential (2) under conditions of high risk and low certainty, loss-framed messages will be influential. This cross-sectional study recruited 283 HIV-negative students from a South African university who were given a questionnaire that contained matched certain gain-framed, certain loss-framed, uncertain gain-framed, and uncertain loss-framed statements based on common barriers and facilitators of WTP. Participants were asked to rate how likely each statement was to result in their participation in a hypothetical preventative HIV vaccine trial. Consistent with Prospect Theory predictions, for certain outcomes, gain-framed messages were more likely to result in WTP than loss-framed messages. Inconsistent with predictions, loss-framed message were not more likely to be related to WTP for uncertain outcomes than gain-framed messages. Older students were less likely to express their WTP across the different message frames. Recruitment for HIV vaccine trials should pay attention to how messages about the trial are presented to potential participants.

  7. Merck Ad5/HIV induces broad innate immune activation that predicts CD8⁺ T-cell responses but is attenuated by preexisting Ad5 immunity.

    Science.gov (United States)

    Zak, Daniel E; Andersen-Nissen, Erica; Peterson, Eric R; Sato, Alicia; Hamilton, M Kristina; Borgerding, Joleen; Krishnamurty, Akshay T; Chang, Joanne T; Adams, Devin J; Hensley, Tiffany R; Salter, Alexander I; Morgan, Cecilia A; Duerr, Ann C; De Rosa, Stephen C; Aderem, Alan; McElrath, M Juliana

    2012-12-11

    To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes. Responses of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5-seropositive subgroups in the Step Study may relate to the lack of appropriate innate activation rather than to increased systemic immune activation. Importantly, patterns of chemoattractant cytokine responses at 24 h and alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were predictive of subsequent induction and magnitude of HIV-specific CD8(+) T-cell responses. This systems approach provides a framework to compare innate responses induced by vectors, as shown here by contrasting the more rapid, robust response to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the findings may permit selection of HIV vaccine candidates eliciting innate immune response profiles more likely to drive HIV protective immunity.

  8. Associations between HIV and schizophrenia and their effect on HIV treatment outcomes

    DEFF Research Database (Denmark)

    Helleberg, Marie; Pedersen, Marianne G; Pedersen, Carsten B

    2015-01-01

    BACKGROUND: Associations between HIV and schizophrenia in people with and without substance use disorders and the effect on timeliness of HIV diagnosis, antiretroviral therapy (ART), and treatment outcomes are poorly understood. We aimed to assess the association between HIV and schizophrenia and...

  9. HIV-1 induces DCIR expression in CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Alexandra A Lambert

    2010-11-01

    Full Text Available The C-type lectin receptor DCIR, which has been shown very recently to act as an attachment factor for HIV-1 in dendritic cells, is expressed predominantly on antigen-presenting cells. However, this concept was recently challenged by the discovery that DCIR can also be detected in CD4(+ T cells found in the synovial tissue from rheumatoid arthritis (RA patients. Given that RA and HIV-1 infections share common features such as a chronic inflammatory condition and polyclonal immune hyperactivation status, we hypothesized that HIV-1 could promote DCIR expression in CD4(+ T cells. We report here that HIV-1 drives DCIR expression in human primary CD4(+ T cells isolated from patients (from both aviremic/treated and viremic/treatment naive persons and cells acutely infected in vitro (seen in both virus-infected and uninfected cells. Soluble factors produced by virus-infected cells are responsible for the noticed DCIR up-regulation on uninfected cells. Infection studies with Vpr- or Nef-deleted viruses revealed that these two viral genes are not contributing to the mechanism of DCIR induction that is seen following acute infection of CD4(+ T cells with HIV-1. Moreover, we report that DCIR is linked to caspase-dependent (induced by a mitochondria-mediated generation of free radicals and -independent intrinsic apoptotic pathways (involving the death effector AIF. Finally, we demonstrate that the higher surface expression of DCIR in CD4(+ T cells is accompanied by an enhancement of virus attachment/entry, replication and transfer. This study shows for the first time that HIV-1 induces DCIR membrane expression in CD4(+ T cells, a process that might promote virus dissemination throughout the infected organism.

  10. CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients

    Science.gov (United States)

    Hunt, Peter W.; Huang, Yong; Simoes, Marisol; Lima, Sheila B.; Freire, Marcos S.; Caiaffa-Filho, Helio H.; Hong, Marisa A.; Costa, Dayane Alves; Dias, Juliana Zanatta C.; Cerqueira, Natalia B.; Nishiya, Anna Shoko; Sabino, Ester Cerdeira; Sartori, Ana M.; Kallas, Esper G.

    2016-01-01

    Background HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation–characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity—may influence vaccine response in this population. Methods We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models. Results 12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV–infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers. Conclusions HIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio. PMID:27941965

  11. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark

    DEFF Research Database (Denmark)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S

    2017-01-01

    in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. METHODS: WLWH between 18......-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes...... RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. CONCLUSION: In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies...

  12. Association between HIV status and Positive Prostate Biopsy in a Study of U.S. Veterans

    Directory of Open Access Journals (Sweden)

    Wayland Hsiao

    2009-01-01

    Full Text Available HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs and corresponding 95% confidence intervals (CI. The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3–11.5. In analyses restricted to prostate cancer patients, HIV-positive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients.

  13. Association between HIV status and Positive Prostate Biopsy in a Study of U.S. Veterans

    Science.gov (United States)

    Hsiao, Wayland; Anastasia, Katrina; Hall, John; Goodman, Michael; Rimland, David; Ritenour, Chad W. M.; Issa, Muta M.

    2009-01-01

    HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs) and corresponding 95% confidence intervals (CI). The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3–11.5). In analyses restricted to prostate cancer patients, HIV-positive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients. PMID:19219374

  14. Prevalence of HIV associated neurocognitive deficit among HIV ...

    African Journals Online (AJOL)

    Background: HIV associated neurocognitive deficit impairs motor activity, neuropsychiatric functioning, daily activity and work activity usually due to the immune suppression effect of the virus. Sub-Saharan region including Ethiopia is the region with the highest burden of HIV. However, a few studies are found on this aspect ...

  15. Polyfunctional HIV-Specific Antibody Responses Are Associated with Spontaneous HIV Control.

    Directory of Open Access Journals (Sweden)

    Margaret E Ackerman

    2016-01-01

    Full Text Available Elite controllers (ECs represent a unique model of a functional cure for HIV-1 infection as these individuals develop HIV-specific immunity able to persistently suppress viremia. Because accumulating evidence suggests that HIV controllers generate antibodies with enhanced capacity to drive antibody-dependent cellular cytotoxicity (ADCC that may contribute to viral containment, we profiled an array of extra-neutralizing antibody effector functions across HIV-infected populations with varying degrees of viral control to define the characteristics of antibodies associated with spontaneous control. While neither the overall magnitude of antibody titer nor individual effector functions were increased in ECs, a more functionally coordinated innate immune-recruiting response was observed. Specifically, ECs demonstrated polyfunctional humoral immune responses able to coordinately recruit ADCC, other NK functions, monocyte and neutrophil phagocytosis, and complement. This functionally coordinated response was associated with qualitatively superior IgG3/IgG1 responses, whereas HIV-specific IgG2/IgG4 responses, prevalent among viremic subjects, were associated with poorer overall antibody activity. Rather than linking viral control to any single activity, this study highlights the critical nature of functionally coordinated antibodies in HIV control and associates this polyfunctionality with preferential induction of potent antibody subclasses, supporting coordinated antibody activity as a goal in strategies directed at an HIV-1 functional cure.

  16. Predictive markers of survival in HIV-seropositive and HIV-seronegative Tanzanian patients with extrapulmonary tuberculosis

    NARCIS (Netherlands)

    Richter, C.; Koelemay, M. J.; Swai, A. B.; Perenboom, R.; Mwakyusa, D. H.; Oosting, J.

    1995-01-01

    Prediction of survival in Tanzanian patients with extrapulmonary tuberculosis (TB). To evaluate the prognostic value of clinical and laboratory parameters on survival in human immunodeficiency virus (HIV) seropositive and HIV seronegative patients with extrapulmonary TB. Over an 8-month period 192

  17. Regional gene expression of LOX-1, VCAM-1, and ICAM-1 in aorta of HIV-1 transgenic rats

    DEFF Research Database (Denmark)

    Hag, Anne Mette Fisker; Kristoffersen, Ulrik Sloth; Pedersen, Sune Folke

    2009-01-01

    endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in HIV-1...... transgenic (HIV-1Tg) rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1......-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular disease....

  18. Expression of HIV gp120 protein increases sensitivity to the rewarding properties of methamphetamine in mice

    Science.gov (United States)

    Kesby, James P.; Hubbard, David T.; Markou, Athina; Semenova, Svetlana

    2012-01-01

    Methamphetamine abuse and human immunodeficiency virus (HIV) infection induce neuropathological changes in corticolimbic brain areas involved in reward and cognitive function. Little is known about the combined effects of methamphetamine and HIV infection on cognitive and reward processes. The HIV/gp120 protein induces neurodegeneration in mice, similar to HIV-induced pathology in humans. We investigated the effects of gp120 expression on associative learning, preference for methamphetamine and non-drug reinforcers, and sensitivity to the conditioned rewarding properties of methamphetamine in transgenic (tg) mice expressing HIV/gp120 protein (gp120-tg). gp120-tg mice learned the operant response for food at the same rate as non-tg mice. In the two-bottle choice procedure with restricted access to drugs, gp120-tg mice exhibited greater preference for methamphetamine and saccharin than non-tg mice, whereas preference for quinine was similar between genotypes. Under conditions of unrestricted access to methamphetamine, the mice exhibited a decreased preference for increasing methamphetamine concentrations. However, male gp120-tg mice showed a decreased preference for methamphetamine at lower concentrations than non-tg male mice. gp120-tg mice developed methamphetamine-induced conditioned place preference at lower methamphetamine doses compared with non-tg mice. No differences in methamphetamine pharmacokinetics were found between genotypes. These results indicate that gp120-tg mice exhibit no deficits in associative learning or reward/motivational function for a natural reinforcer. Interestingly, gp120 expression resulted in increased preference for methamphetamine and a highly palatable non-drug reinforcer (saccharin) and increased sensitivity to methamphetamine-induced conditioned reward. These data suggest that HIV-positive individuals may have increased sensitivity to methamphetamine, leading to high methamphetamine abuse potential in this population. PMID

  19. The association between HIV/AIDS-related knowledge and perception of risk for infection

    DEFF Research Database (Denmark)

    Ndugwa Kabwama, Steven; Berg-Beckhoff, Gabriele

    2015-01-01

    This systematic review tries to elucidate the association between what people know about HIV/AIDS and how they perceive their risk of infection. The initial search for articles yielded 1,595 abstracts, 16 of which met the inclusion criteria. Five studies found a positive correlation, four reported...... a negative correlation and seven found no association between knowledge and risk perception. It was found that the existing psychometrically sound measure of HIV/AIDS risk perception had not been used in any of the studies. The context in which the risk is assessed is pivotal to whether an association...... between knowledge and the perceived risk is found. Biases in judgement such as optimistic bias, psychological distancing, anchoring bias and overconfidence also explain how knowledge may fail to predict risk perception. It was concluded that the association between HIV/AIDS knowledge and risk perception...

  20. Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis.

    Directory of Open Access Journals (Sweden)

    Joseph N Jarvis

    2015-04-01

    Full Text Available Understanding the host immune response during cryptococcal meningitis (CM is of critical importance for the development of immunomodulatory therapies. We profiled the cerebrospinal fluid (CSF immune-response in ninety patients with HIV-associated CM, and examined associations between immune phenotype and clinical outcome. CSF cytokine, chemokine, and macrophage activation marker concentrations were assayed at disease presentation, and associations between these parameters and microbiological and clinical outcomes were examined using principal component analysis (PCA. PCA demonstrated a co-correlated CSF cytokine and chemokine response consisting primarily of Th1, Th2, and Th17-type cytokines. The presence of this CSF cytokine response was associated with evidence of increased macrophage activation, more rapid clearance of Cryptococci from CSF, and survival at 2 weeks. The key components of this protective immune-response were interleukin (IL-6 and interferon-γ, IL-4, IL-10 and IL-17 levels also made a modest positive contribution to the PC1 score. A second component of co-correlated chemokines was identified by PCA, consisting primarily of monocyte chemotactic protein-1 (MCP-1 and macrophage inflammatory protein-1α (MIP-1α. High CSF chemokine concentrations were associated with low peripheral CD4 cell counts and CSF lymphocyte counts and were predictive of immune reconstitution inflammatory syndrome (IRIS. In conclusion CSF cytokine and chemokine profiles predict risk of early mortality and IRIS in HIV-associated CM. We speculate that the presence of even minimal Cryptococcus-specific Th1-type CD4+ T-cell responses lead to increased recruitment of circulating lymphocytes and monocytes into the central nervous system (CNS, more effective activation of CNS macrophages and microglial cells, and faster organism clearance; while high CNS chemokine levels may predispose to over recruitment or inappropriate recruitment of immune cells to the CNS and

  1. HIV-Related Stress and Life Chaos Mediate the Association Between Poverty and Medication Adherence Among People Living with HIV/AIDS.

    Science.gov (United States)

    Kalichman, Seth C; Kalichman, Moira O

    2016-12-01

    HIV treatment depends on high-levels of antiretroviral therapy (ART) adherence, which is severely impeded by poverty. Men and women living with HIV infection (N = 92) completed computerized interviews of demographic and health characteristics, poverty markers, stressful life events, and life chaos, as well as unannounced pill counts to determine prospective medication adherence and medical record chart abstractions for HIV viral load. Poverty markers were associated with both stressors and chaos, and the direct effects of all three factors predicted ART non-adherence. The multiple mediation model showed that accounting for stressors and chaos resulted in a non-significant association between poverty markers and ART adherence. The indirect effect of poverty markers on adherence through life chaos was significant, whereas the indirect effect of poverty markers on adherence through stressors was not significant. Factors that render HIV-related stress and create chaos offer intervention targets that are more amenable to change than poverty itself.

  2. Macaques can predict social outcomes from facial expressions.

    Science.gov (United States)

    Waller, Bridget M; Whitehouse, Jamie; Micheletta, Jérôme

    2016-09-01

    There is widespread acceptance that facial expressions are useful in social interactions, but empirical demonstration of their adaptive function has remained elusive. Here, we investigated whether macaques can use the facial expressions of others to predict the future outcomes of social interaction. Crested macaques (Macaca nigra) were shown an approach between two unknown individuals on a touchscreen and were required to choose between one of two potential social outcomes. The facial expressions of the actors were manipulated in the last frame of the video. One subject reached the experimental stage and accurately predicted different social outcomes depending on which facial expressions the actors displayed. The bared-teeth display (homologue of the human smile) was most strongly associated with predicted friendly outcomes. Contrary to our predictions, screams and threat faces were not associated more with conflict outcomes. Overall, therefore, the presence of any facial expression (compared to neutral) caused the subject to choose friendly outcomes more than negative outcomes. Facial expression in general, therefore, indicated a reduced likelihood of social conflict. The findings dispute traditional theories that view expressions only as indicators of present emotion and instead suggest that expressions form part of complex social interactions where individuals think beyond the present.

  3. Quality of Caregiving is Positively Associated With Neurodevelopment During the First Year of Life Among HIV-Exposed Uninfected Children in Uganda.

    Science.gov (United States)

    Familiar, Itziar; Collins, Shalean M; Sikorskii, Alla; Ruisenor-Escudero, Horacio; Natamba, Barnabas; Bangirana, Paul; Widen, Elizabeth M; Achidri, Daniel; Achola, Harriet; Onen, Daniel; Boivin, Michael; Young, Sera L

    2018-03-01

    We sought to evaluate whether maternal characteristics and infant developmental milieu were predictive of early cognitive development in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HU) infants in Uganda. Longitudinal pregnancy study. Ugandan women (n = 228) were enrolled into the Postnatal Nutrition and Psychosocial Health Outcomes study with a 2:1 HIV-uninfected: infected ratio. Maternal sociodemographic, perceived social support, and depressive symptomatology were assessed. Infant growth and neurocognitive development were assessed at 6 and 12 months of age using Mullen Scales of Early Learning (MSEL). Caldwell Home Observation for Home Environment was used to gauge caregiving quality. Linear mixed-effects models were built to examine the relationships between maternal and infant characteristics with infant MSEL scores by HIV exposure. Two MSEL measures were available for 215 mother-child dyads: 140 infants (65%) were HIV-uninfected (HU), 57 (27%) were HIV-exposed uninfected (HEU) with mothers reporting antiretroviral therapy, and 18 (8%) were HEU with mothers not reporting antiretroviral therapy. HEU had lower MSEL Composite (β = -3.94, P = 0.03) and Gross Motor scores (β = -3.41, P = 0.01) than HU. Home Observation for Home Environment total score was positively associated with MSEL Composite (β = 0.81, P = 0.01), Receptive Language (β = 0.59, P = 0.001), and Expressive Language (β = 0.64, P = 0.01) scores. HIV exposure is associated with lower infant cognitive development scores. Increasing maternal quality of caregiving may improve early cognitive development.

  4. Hiv-Associated Pulmonary Hypertension: Case Report | Shavadia ...

    African Journals Online (AJOL)

    With the advent of highly active antiretroviral therapy, there has been a significant change in the epidemiology of pulmonary disease in HIV/AIDS. The relative prevalence of non-infectious manifestations is likely to rise. HIV associated pulmonary hypertension (HIV-PH), albeit low prevalence, is associated with significant ...

  5. Proteomic analysis of PBMCs: characterization of potential HIV-associated proteins

    Directory of Open Access Journals (Sweden)

    Yin Lin

    2010-03-01

    Full Text Available Abstract Background The human immunodeficiency virus type 1 (HIV-1 pandemic has continued unabated for nearly 30 years. To better understand the influence of virus on host cells, we performed the differential proteome research of peripheral blood mononuclear cells (PBMCs from HIV-positive patients and healthy controls. Results 26 protein spots with more than 1.5-fold difference were detected in two dimensional electrophoresis (2DE gels. 12 unique up-regulated and one down-regulated proteins were identified in HIV-positive patients compared with healthy donors. The mRNA expression of 10 genes was analyzed by real time RT-PCR. It shows that the mRNA expression of talin-1, vinculin and coronin-1C were up-regulated in HIV positive patients and consistent with protein expression. Western blotting analysis confirmed the induction of fragments of vinculin, talin-1 and filamin-A in pooled and most part of individual HIV-positive clinical samples. Bioinformatic analysis showed that a wide host protein network was disrupted in HIV-positive patients. Conclusions Together, this work provided useful information to facilitate further investigation of the underlying mechanism of HIV and host cell protein interactions, and discovered novel potential biomarkers such as fragment of vinculin, filamin-A and talin-1 for anti-HIV research.

  6. HIV impairs opsonic phagocytic clearance of pregnancy-associated malaria parasites.

    Directory of Open Access Journals (Sweden)

    Jessica Keen

    2007-05-01

    Full Text Available BACKGROUND: Primigravid (PG women are at risk for pregnancy-associated malaria (PAM. Multigravid (MG women acquire protection against PAM; however, HIV infection impairs this protective response. Protection against PAM is associated with the production of IgG specific for variant surface antigens (VSA-PAM expressed by chondroitin sulfate A (CSA-adhering parasitized erythrocytes (PEs. We hypothesized that VSA-PAM-specific IgG confers protection by promoting opsonic phagocytosis of PAM isolates and that HIV infection impairs this response. METHODS AND FINDINGS: We assessed the ability of VSA-PAM-specific IgG to promote opsonic phagocytosis of CSA-adhering PEs and the impact of HIV infection on this process. Opsonic phagocytosis assays were performed using the CSA-adherent parasite line CS2 and human and murine macrophages. CS2 PEs were opsonized with plasma or purified IgG subclasses from HIV-negative or HIV-infected PG and MG Kenyan women or sympatric men. Levels of IgG subclasses specific for VSA-PAM were compared in HIV-negative and HIV-infected women by flow cytometry. Plasma from HIV-negative MG women, but not PG women or men, promoted the opsonic phagocytosis of CSA-binding PEs (p < 0.001. This function depended on VSA-PAM-specific plasma IgG1 and IgG3. HIV-infected MG women had significantly lower plasma opsonizing activity (median phagocytic index 46 [interquartile range (IQR 18-195] versus 251 [IQR 93-397], p = 0.006 and levels of VSA-PAM-specific IgG1 (mean fluorescence intensity [MFI] 13 [IQR 11-20] versus 30 [IQR 23-41], p < 0.001 and IgG3 (MFI 17 [IQR 14-23] versus 28 [IQR 23-37], p < 0.001 than their HIV-negative MG counterparts. CONCLUSIONS: Opsonic phagocytosis may represent a novel correlate of protection against PAM. HIV infection may increase the susceptibility of multigravid women to PAM by impairing this clearance mechanism.

  7. CD52 expression on CD4+ T cells in HIV-positive individuals on cART

    DEFF Research Database (Denmark)

    Vojdeman, Fie Juhl; Gaardbo, Julie Christine; Hartling, Hans Jakob

    2018-01-01

    BACKGROUND: Human immune defect virus (HIV) persists in a latent state in quiescent CD4+ T cells preventing eradication of HIV. CD52 is a surface molecule modulated by HIV. We aimed at examining factors related to CD52 expression on CD4+ T cells in HIV-positive individuals and the impact...... of initiation of combination antiretroviral therapy (cART). METHODS: Peripheral blood mononuclear cells (PBMC) from 18 HIV-positive individuals and 10 uninfected age and gender matched controls were examined by flow cytometry for CD38 and CD52 expression on CD4+ T cells. Stimulation assays were performed on 8...... healthy blood donors to determine a cut-off for CD52 expression. RESULTS: All examined CD4+ T cells expressed CD52. However, both CD4+ T cells with higher (CD52++) and with lower CD52 expression (CD52dim) were found in HIV-positive individuals compared to uninfected controls. Two % CD52dim cells defined...

  8. Increased brain-predicted aging in treated HIV disease

    NARCIS (Netherlands)

    Cole, James H; Underwood, Jonathan; Caan, Matthan W A; De Francesco, Davide; van Zoest, Rosan A; Leech, Robert; Wit, Ferdinand W N M; Portegies, Peter; Geurtsen, Gert J; Schmand, Ben A; Schim van der Loeff, Maarten F; Franceschi, Claudio; Sabin, Caroline A; Majoie, Charles B L M; Winston, Alan; Reiss, Peter; Sharp, David J; Kalsbeek, A.

    OBJECTIVE: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. METHODS: A

  9. Increased brain-predicted aging in treated HIV disease

    NARCIS (Netherlands)

    Cole, James H.; Underwood, Jonathan; Caan, Matthan W. A.; de Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W. N. M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B. L. M.; Winston, Alan; Reiss, Peter; Sharp, David J.; Schouten, J.; Kooij, K. W.; Elsenga, B. C.; Janssen, F. R.; Heidenrijk, M.; Schrijver, J. H. N.; Zikkenheiner, W.; van der Valk, M.; Henderiks, A.; Kootstra, N. A.; Harskamp-Holwerda, A. M.; Maurer, I.; Ruiz, M. M. Mangas; Booiman, T.; Girigorie, A. F.; Villaudy, J.; Frankin, E.; Pasternak, A.; Berkhout, B.; van der Kuyl, T.; Stege, J. A. ter; Twennaar, M. Klein; Su, T.; Siteur-van Rijnstra, E.; Weijer, K.; Bisschop, P. H. L. T.; Kalsbeek, A.; Wezel, M.; Visser, I.; Ruhé , H. G.; Tembo, L.; Stott, M.; Prins, M. [= Maria

    2017-01-01

    To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. A large sample of

  10. Cell-cycle and suppressor proteins expression in uterine cervix in HIV/HPV co-infection: comparative study by tissue micro-array (TMA)

    International Nuclear Information System (INIS)

    Nicol, Alcina F; Pirmez, Claude; Pires, Andréa Rodrigues Cordovil; Souza, Simone R de; Nuovo, Gerard J; Grinsztejn, Beatriz; Tristão, Aparecida; Russomano, Fabio B; Velasque, Luciane; Silva, José R Lapa e

    2008-01-01

    The oncoproteins of human papillomavirus (HPVs) directly effect cell-cycle control. We hypothesize that regulatory and cell cycle protein expression might be additionally modified in the cervix of HIV/HPV co-infected women. We analyzed the expression of Rb, p27, VEGF and Elf-1 transcriptor factor by immunohistochemistry in 163 paraffin-embeded cervical samples using Tissue Micro-Array (TMA) and correlated this to HIV-1 and HPV infection. HIV/HPV co-infection was associated with a significant increase in expression (p < 0.001) of VEGF and p27 in both low and high grade CIN when compared to the cervices of women infected by HPV alone. Decreased Rb expression was evident with increased CIN grade in the cervices of women infected with HPV alone (p = 0.003 average of cells/mm 2 in CIN I: 17.9, CIN II/III: 4.8, and tumor 3.9). Rb expression increased 3-fold for both low and high grade CIN with HPV/HIV-1 co-infection compared to HPV infection alone but did not reach statistical significance. There was a significant increase in Elf-1 expression in HPV+/HIV- women with CIN II/III and tumor (average of cells/mm 2 in CIN I: 63.8; CIN II/III: 115.7 and tumor: 112.0, p = 0.005), in comparison to controls. Co-infection of HPV and HIV leads to significant increase in the VEGF and p27 expression when compared to HPV+/HIV-negative infection that could facilitate viral persistence and invasive tumor development

  11. Cell-cycle and suppressor proteins expression in uterine cervix in HIV/HPV co-infection: comparative study by tissue micro-array (TMA).

    Science.gov (United States)

    Nicol, Alcina F; Pires, Andréa Rodrigues Cordovil; de Souza, Simone R; Nuovo, Gerard J; Grinsztejn, Beatriz; Tristão, Aparecida; Russomano, Fabio B; Velasque, Luciane; Lapa e Silva, José R; Pirmez, Claude

    2008-10-07

    The oncoproteins of human papillomavirus (HPVs) directly effect cell-cycle control. We hypothesize that regulatory and cell cycle protein expression might be additionally modified in the cervix of HIV/HPV co-infected women. We analyzed the expression of Rb, p27, VEGF and Elf-1 transcriptor factor by immunohistochemistry in 163 paraffin-embeded cervical samples using Tissue Micro-Array (TMA) and correlated this to HIV-1 and HPV infection. HIV/HPV co-infection was associated with a significant increase in expression (p < 0.001) of VEGF and p27 in both low and high grade CIN when compared to the cervices of women infected by HPV alone. Decreased Rb expression was evident with increased CIN grade in the cervices of women infected with HPV alone (p = 0.003 average of cells/mm2 in CIN I: 17.9, CIN II/III: 4.8, and tumor 3.9). Rb expression increased 3-fold for both low and high grade CIN with HPV/HIV-1 co-infection compared to HPV infection alone but did not reach statistical significance. There was a significant increase in Elf-1 expression in HPV+/HIV- women with CIN II/III and tumor (average of cells/mm2 in CIN I: 63.8; CIN II/III: 115.7 and tumor: 112.0, p = 0.005), in comparison to controls. Co-infection of HPV and HIV leads to significant increase in the VEGF and p27 expression when compared to HPV+/HIV-negative infection that could facilitate viral persistence and invasive tumor development.

  12. Prediction of the Secondary Structure of HIV-1 gp120

    DEFF Research Database (Denmark)

    Hansen, Jan; Lund, Ole; Nielsen, Jens O.

    1996-01-01

    Fourier transform infrared spectroscopy. The predicted secondary structure of gp120 compared well with data from NMR analysis of synthetic peptides from the V3 loop and the C4 region. As a first step towards modeling the tertiary structure of gp120, the predicted secondary structure may guide the design......The secondary structure of HIV-1 gp120 was predicted using multiple alignment and a combination of two independent methods based on neural network and nearest-neighbor algorithms. The methods agreed on the secondary structure for 80% of the residues in BH10 gp120. Six helices were predicted in HIV...

  13. Interleukin-27 is differentially associated with HIV viral load and CD4+ T cell counts in therapy-naive HIV-mono-infected and HIV/HCV-co-infected Chinese.

    Directory of Open Access Journals (Sweden)

    Lai He

    Full Text Available Human Immunodeficiency Virus (HIV infection and the resultant Acquired Immunodeficiency Syndrome (AIDS epidemic are major global health challenges; hepatitis C virus (HCV co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27, a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.

  14. Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors.

    Directory of Open Access Journals (Sweden)

    Esther D Quakkelaar

    Full Text Available Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses in vitro from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs, RNA expression arrays, HIV gag expression and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells in vitro. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines.

  15. Changes in the topology of gene expression networks by human immunodeficiency virus type 1 (HIV-1) integration in macrophages.

    Science.gov (United States)

    Soto-Girón, María Juliana; García-Vallejo, Felipe

    2012-01-01

    One key step of human immunodeficiency virus type 1 (HIV-1) infection is the integration of its viral cDNA. This process is mediated through complex networks of host-virus interactions that alter several normal cell functions of the host. To study the complexity of disturbances in cell gene expression networks by HIV-1 integration, we constructed a network of human macrophage genes located close to chromatin regions rich in proviruses. To perform the network analysis, we selected 28 genes previously identified as the target of cDNA integration and their transcriptional profiles were obtained from GEO Profiles (NCBI). A total of 2770 interactions among the 28 genes located around the HIV-1 proviruses in human macrophages formed a highly dense main network connected to five sub-networks. The overall network was significantly enriched by genes associated with signal transduction, cellular communication and regulatory processes. To simulate the effects of HIV-1 integration in infected macrophages, five genes with the most number of interaction in the normal network were turned off by putting in zero the correspondent expression values. The HIV-1 infected network showed changes in its topology and alteration in the macrophage functions reflected in a re-programming of biosynthetic and general metabolic process. Understanding the complex virus-host interactions that occur during HIV-1 integration, may provided valuable genomic information to develop new antiviral treatments focusing on the management of some specific gene expression networks associated with viral integration. This is the first gene network which describes the human macrophages genes interactions related with HIV-1 integration. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. RRE-dependent HIV-1 Env RNA effects on Gag protein expression, assembly and release

    International Nuclear Information System (INIS)

    López, Claudia S.; Sloan, Rachel; Cylinder, Isabel; Kozak, Susan L.; Kabat, David; Barklis, Eric

    2014-01-01

    The HIV-1 Gag proteins are translated from the full-length HIV-1 viral RNA (vRNA), whereas the envelope (Env) protein is translated from incompletely spliced Env mRNAs. Nuclear export of vRNAs and Env mRNAs is mediated by the Rev accessory protein which binds to the rev-responsive element (RRE) present on these RNAs. Evidence has shown there is a direct or indirect interaction between the Gag protein, and the cytoplasmic tail (CT) of the Env protein. Our current work shows that env gene expression impacts HIV-1 Gag expression and function in two ways. At the protein level, full-length Env expression altered Gag protein expression, while Env CT-deletion proteins did not. At the RNA level, RRE-containing Env mRNA expression reduced Gag expression, processing, and virus particle release from cells. Our results support models in which Gag is influenced by the Env CT, and Env mRNAs compete with vRNAs for nuclear export. - Highlights: • At the protein level, full-length HIV-1 Env alters Gag protein expression. • HIV-1 Env RNA expression reduces Gag levels and virus release. • Env RNA effects on Gag are dependent on the RRE. • RRE-containing Env RNAs compete with vRNAs for nuclear export

  17. Inhibition of HIV Expression and Integration in Macrophages by Methylglyoxal-Bis-Guanylhydrazone.

    Science.gov (United States)

    Jin, Xia; McGrath, Michael S; Xu, Hua

    2015-11-01

    Macrophages are a target for infection with HIV and represent one of the viral reservoirs that are relatively resistant to current antiretroviral drugs. Here we demonstrate that methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine analog and potent S-adenosylmethionine decarboxylase inhibitor, decreases HIV expression in monocytes and macrophages. MGBG is selectively concentrated by these cells through a mechanism consistent with active transport by the polyamine transporter. Using a macrophage-tropic reporter virus tagged with the enhanced green fluorescent protein, we demonstrate that MGBG decreases the frequency of HIV-infected cells. The effect is dose dependent and correlates with the production of HIV p24 in culture supernatants. This anti-HIV effect was further confirmed using three macrophage-tropic primary HIV isolates. Viral life cycle mapping studies show that MGBG inhibits HIV DNA integration into the cellular DNA in both monocytes and macrophages. Our work demonstrates for the first time the selective concentration of MGBG by monocytes/macrophages, leading to the inhibition of HIV-1 expression and a reduction in proviral load within macrophage cultures. These results suggest that MGBG may be useful in adjunctive macrophage-targeted therapy for HIV infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. HIV-1 with multiple CCR5/CXCR4 chimeric receptor use is predictive of immunological failure in infected children.

    Science.gov (United States)

    Cavarelli, Mariangela; Karlsson, Ingrid; Zanchetta, Marisa; Antonsson, Liselotte; Plebani, Anna; Giaquinto, Carlo; Fenyö, Eva Maria; De Rossi, Anita; Scarlatti, Gabriella

    2008-09-29

    HIV-1 R5 viruses are characterized by a large phenotypic variation, that is reflected by the mode of coreceptor use. The ability of R5 HIV-1 to infect target cells expressing chimeric receptors between CCR5 and CXCR4 (R5(broad) viruses), was shown to correlate with disease stage in HIV-1 infected adults. Here, we ask the question whether phenotypic variation of R5 viruses could play a role also in mother-to-child transmission (MTCT) of HIV-1 and pediatric disease progression. Viral isolates obtained from a total of 59 HIV-1 seropositive women (24 transmitting and 35 non transmitting) and 28 infected newborn children, were used to infect U87.CD4 cells expressing wild type or six different CCR5/CXCR4 chimeric receptors. HIV-1 isolates obtained from newborn infants had predominantly R5(narrow) phenotype (n = 20), but R5(broad) and R5X4 viruses were also found in seven and one case, respectively. The presence of R5(broad) and R5X4 phenotypes correlated significantly with a severe decline of the CD4+ T cells (CDC stage 3) or death within 2 years of age. Forty-three percent of the maternal R5 isolates displayed an R5(broad) phenotype, however, the presence of the R5(broad) virus was not predictive for MTCT of HIV-1. Of interest, while only 1 of 5 mothers with an R5X4 virus transmitted the dualtropic virus, 5 of 6 mothers carrying R5(broad) viruses transmitted viruses with a similar broad chimeric coreceptor usage. Thus, the maternal R5(broad) phenotype was largely preserved during transmission and could be predictive of the phenotype of the newborn's viral variant. Our results show that R5(broad) viruses are not hampered in transmission. When transmitted, immunological failure occurs earlier than in children infected with HIV-1 of R5(narrow) phenotype. We believe that this finding is of utmost relevance for therapeutic interventions in pediatric HIV-1 infection.

  19. Sex Differences in Emotional and Behavioral Responses to HIV+ individuals’ Expression of Distress

    NARCIS (Netherlands)

    A.E.R. Bos (Arjan); A.J. Dijker (Anton); W. Koomen (Willem)

    2007-01-01

    textabstractTwo studies examined the influence of HIV+ individual’s expression of distress on perceivers’ emotional and behavioral reactions. In Study 1 (N = 224), HIV+ individuals’ expression of distress was experimentally manipulated by means of vignettes. Men and women reacted differently when

  20. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

    Science.gov (United States)

    Verma, Meghna; Erwin, Samantha; Abedi, Vida; Hontecillas, Raquel; Hoops, Stefan; Leber, Andrew; Bassaganya-Riera, Josep; Ciupe, Stanca M

    2017-01-01

    Human immunodeficiency virus (HIV)-infected patients are at an increased risk of co-infection with human papilloma virus (HPV), and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1) cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

  1. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

    Directory of Open Access Journals (Sweden)

    Meghna Verma

    Full Text Available Human immunodeficiency virus (HIV-infected patients are at an increased risk of co-infection with human papilloma virus (HPV, and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1 cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

  2. HIV-1 transgene expression in rats causes oxidant stress and alveolar epithelial barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Jacob Barbara A

    2009-02-01

    Full Text Available Abstract Background HIV-infected individuals are at increased risk for acute and chronic airway disease even though there is no evidence that the virus can infect the lung epithelium. Although HIV-related proteins including gp120 and Tat can directly cause oxidant stress and cellular dysfunction, their effects in the lung are unknown. The goal of this study was to determine the effects of HIV-1 transgene expression in rats on alveolar epithelial barrier function. Alveolar epithelial barrier function was assessed by determining lung liquid clearance in vivo and alveolar epithelial monolayer permeability in vitro. Oxidant stress in the alveolar space was determined by measuring the glutathione redox couple by high performance liquid chromatography, and the expression and membrane localization of key tight junction proteins were assessed. Finally, the direct effects of the HIV-related proteins gp120 and Tat on alveolar epithelial barrier formation and tight junction protein expression were determined. Results HIV-1 transgene expression caused oxidant stress within the alveolar space and impaired epithelial barrier function even though there was no evidence of overt inflammation within the airways. The expression and membrane localization of the tight junction proteins zonula occludens-1 and occludin were decreased in alveolar epithelial cells from HIV-1 transgenic rats. Further, treating alveolar epithelial monolayers from wild type rats in vitro with recombinant gp120 or Tat for 24 hours reproduced many of the effects on zonula occludens-1 and occludin expression and membrane localization. Conclusion Taken together, these data indicate that HIV-related proteins cause oxidant stress and alter the expression of critical tight junction proteins in the alveolar epithelium, resulting in barrier dysfunction.

  3. Low expression of IL-18 and IL-18 receptor in human skeletal muscle is associated with systemic and intramuscular lipid metabolism-Role of HIV lipodystrophy

    DEFF Research Database (Denmark)

    Lindegaard, Birgitte; Hvid, Thine; Wolsk Mygind, Helene

    2018-01-01

    receptor (R) expression would be altered in patients with HIV-lipodystrophy. DESIGN AND METHODS: Twenty-three HIV-infected patients with LD and 15 age-matched healthy controls were included in a cross-sectional study. Biopsies from the vastus lateralis muscle were obtained and IL-18 and IL-18R m......-18 mRNA is expressed in human skeletal muscle but a role for IL-18 in muscle has not been identified. Patients with HIV-infection and lipodystrophy (LD) are characterized by lipid and glucose disturbances and increased levels of circulating IL-18. We hypothesized that skeletal muscle IL-18 and IL-18......RNA expression were measured by real-time PCR and sphingolipids (ceramides, sphingosine, sphingosine-1-Phosphate, sphinganine) were measured by HPLC. Insulin resistance was assessed by HOMA and the insulin response during an OGTT. RESULTS: Patients with HIV-LD had a 60% and 54% lower level of muscular IL-18...

  4. Associations between HIV-RNA-based indicators and virological and clinical outcomes

    DEFF Research Database (Denmark)

    Laut, Kamilla G; Shepherd, Leah C; Pedersen, Court

    2016-01-01

    OBJECTIVES: To evaluate and compare the performance of six HIV-RNA-based quality of care indicators for predicting short-term and long-term outcomes. DESIGN: Multinational cohort study. METHODS: We included EuroSIDA patients on antiretroviral therapy (ART) with at least three viral load measureme......OBJECTIVES: To evaluate and compare the performance of six HIV-RNA-based quality of care indicators for predicting short-term and long-term outcomes. DESIGN: Multinational cohort study. METHODS: We included EuroSIDA patients on antiretroviral therapy (ART) with at least three viral load...... measurements after baseline (the latest of 01/01/2001 or entry into EuroSIDA). Using multivariate Poisson regression, we modelled the association between short-term (resistance, triple-class failure) and long-term (all-cause mortality, any AIDS/non-AIDS clinical event) outcomes and the indicators: viraemia...

  5. Correlates of HIV stigma in HIV-positive women.

    Science.gov (United States)

    Wagner, Anne C; Hart, Trevor A; Mohammed, Saira; Ivanova, Elena; Wong, Joanna; Loutfy, Mona R

    2010-06-01

    We examined the variables associated with HIV stigma in HIV-positive women currently living in Ontario, Canada. Based on previous literature, we predicted that variables of social marginalization (e.g., ethnicity, income, education), medical variables (e.g., higher CD4 count, lower viral load), and increased psychological distress would be associated with higher perceived HIV stigma among HIV-positive women. One hundred fifty-nine HIV-positive women between the ages of 18 and 52 in Ontario completed self-report measures of the aforementioned variables. Women were recruited through 28 AIDS service organizations, eight HIV clinics, and two community health centers. In multiple regression analyses, for women born in Canada, lower educational level and higher anxiety were associated with higher HIV stigma. For women born outside of Canada, having been judged by a physician in Canada for trying to become pregnant was associated with higher HIV stigma. For HIV-positive women born outside of Canada, negative judgment by a physician regarding intentions to become pregnant should be addressed to reduce perceived HIV stigma and vice versa. Health care providers should be trained in the provision of sensitive and effective health care for women living with HIV, especially when providing reproductive health care.

  6. HIV-1 Tat C-mediated regulation of tumor necrosis factor receptor-associated factor-3 by microRNA 32 in human microglia

    Directory of Open Access Journals (Sweden)

    Mishra Ritu

    2012-06-01

    Full Text Available Abstract Background HIV-1 Tat protein is known to be associated with neuroinflammation, a condition that develops in almost half of patients infected with HIV-1. HIV-1 Tat can alter glial neuroprotective functions, leading to neurotoxicity within the CNS. HIV-1 Tat is known to be secreted from productively infected cells and can affect neighboring uninfected cells by modulating cellular gene expression in a bystander fashion. Methods We were interested to study whether exogenous exposure to HIV-1 Tat-C protein perturbs the microRNA (miRNA expression profile of human microglial cells, leading to altered protein expression. We used protein expression and purification, miRNA overexpression, miRNA knockdown, transfection, site-directed mutagenesis, real-time PCR, luciferase assay and western blotting techniques to perform our study. Results HIV-1 Tat-C treatment of human microglial cells resulted in a dose-dependent increase in miR-32 expression. We found that tumor necrosis factor-receptor–associated factor 3 TRAF3 is a direct target for miR-32, and overexpression of miR-32 in CHME3 cells decreased TRAF3 both at the mRNA and the protein level. Recovery of TRAF3 protein expression after transfection of anti-miR-32 and the results of the luciferase reporter assay provided direct evidence of TRAF3 regulation by miR-32. We found that the regulation of interferon regulatory factor 3 (IRF3 and IRF7 is controlled by cellular levels of TRAF3 protein in microglial cells, as after overexpression of miR-32 and application of anti-miR-32, expression levels of IRF3 and IRF7 were inversely regulated by expression levels of TRAF3. Thus, our results suggest a novel miRNA mediated mechanism for regulation of TRAF3 in human microglial cells exposed to HIV-1 Tat C protein. These results may help to elucidate the detrimental neuroinflammatory consequences of HIV-1 Tat C protein in bystander fashion. Conclusion HIV-1 Tat protein can modulate TRAF3 expression through

  7. The predictive nature of transcript expression levels on protein expression in adult human brain.

    Science.gov (United States)

    Bauernfeind, Amy L; Babbitt, Courtney C

    2017-04-24

    Next generation sequencing methods are the gold standard for evaluating expression of the transcriptome. When determining the biological implications of such studies, the assumption is often made that transcript expression levels correspond to protein levels in a meaningful way. However, the strength of the overall correlation between transcript and protein expression is inconsistent, particularly in brain samples. Following high-throughput transcriptomic (RNA-Seq) and proteomic (liquid chromatography coupled with tandem mass spectrometry) analyses of adult human brain samples, we compared the correlation in the expression of transcripts and proteins that support various biological processes, molecular functions, and that are located in different areas of the cell. Although most categories of transcripts have extremely weak predictive value for the expression of their associated proteins (R 2 values of < 10%), transcripts coding for protein kinases and membrane-associated proteins, including those that are part of receptors or ion transporters, are among those that are most predictive of downstream protein expression levels. The predictive value of transcript expression for corresponding proteins is variable in human brain samples, reflecting the complex regulation of protein expression. However, we found that transcriptomic analyses are appropriate for assessing the expression levels of certain classes of proteins, including those that modify proteins, such as kinases and phosphatases, regulate metabolic and synaptic activity, or are associated with a cellular membrane. These findings can be used to guide the interpretation of gene expression results from primate brain samples.

  8. CD4+ and CD8+ T cell activation are associated with HIV DNA in resting CD4+ T cells.

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    Leslie R Cockerham

    Full Text Available The association between the host immune environment and the size of the HIV reservoir during effective antiretroviral therapy is not clear. Progress has also been limited by the lack of a well-accepted assay for quantifying HIV during therapy. We examined the association between multiple measurements of HIV and T cell activation (as defined by markers including CD38, HLA-DR, CCR5 and PD-1 in 30 antiretroviral-treated HIV-infected adults. We found a consistent association between the frequency of CD4+ and CD8+ T cells expressing HLA-DR and the frequency of resting CD4+ T cells containing HIV DNA. This study highlights the need to further examine this relationship and to better characterize the biology of markers commonly used in HIV studies. These results may also have implications for reactivation strategies.

  9. The effects of HIV-1 regulatory TAT protein expression on brain reward function, response to psychostimulants and delay-dependent memory in mice.

    Science.gov (United States)

    Kesby, James P; Markou, Athina; Semenova, Svetlana

    2016-10-01

    Depression and psychostimulant abuse are common comorbidities among humans with immunodeficiency virus (HIV) disease. The HIV regulatory protein TAT is one of multiple HIV-related proteins associated with HIV-induced neurotoxicity. TAT-induced dysfunction of dopamine and serotonin systems in corticolimbic brain areas may result in impaired reward function, thus, contributing to depressive symptoms and psychostimulant abuse. Transgenic mice with doxycycline-induced TAT protein expression in the brain (TAT+, TAT- control) show neuropathology resembling brain abnormalities in HIV+ humans. We evaluated brain reward function in response to TAT expression, nicotine and methamphetamine administration in TAT+ and TAT- mice using the intracranial self-stimulation procedure. We evaluated the brain dopamine and serotonin systems with high-performance liquid chromatography. The effects of TAT expression on delay-dependent working memory in TAT+ and TAT- mice using the operant delayed nonmatch-to-position task were also assessed. During doxycycline administration, reward thresholds were elevated by 20% in TAT+ mice compared with TAT- mice. After the termination of doxycycline treatment, thresholds of TAT+ mice remained significantly higher than those of TAT- mice and this was associated with changes in mesolimbic serotonin and dopamine levels. TAT+ mice showed a greater methamphetamine-induced threshold lowering compared with TAT- mice. TAT expression did not alter delay-dependent working memory. These results indicate that TAT expression in mice leads to reward deficits, a core symptom of depression, and a greater sensitivity to methamphetamine-induced reward enhancement. Our findings suggest that the TAT protein may contribute to increased depressive-like symptoms and continued methamphetamine use in HIV-positive individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV

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    Yue Chen

    2016-11-01

    Full Text Available Abstract Background Infection with human immunodeficiency virus (HIV influences the outcome and natural disease progression of hepatitis C virus (HCV infection. While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop chronic HCV infection, 20–46% of mono- and co-infected subjects spontaneously clear HCV infection. The mechanism underlying viral clearance is not clearly understood. Analysis of differential cellular gene expression (mRNA between HIV-infected patients with persistent HCV infection or spontaneous clearance could provide a unique opportunity to decipher the mechanism of HCV clearance. Methods Plasma RNA from HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV was sequenced using Ion Torrent technology. The sequencing results were analyzed to identify transcripts that are associated with HCV clearance by measuring differential gene expression in HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV. Results We have identified plasma mRNA, the levels of which are significantly elevated (at least 5 fold, False Discovery Rate (FDR <0.05 before HCV infection in subjects who cleared HCV compared to those who remained chronically infected. Upon further analysis of these differentially expressed genes, before and after HCV infection, we found that before HCV infection 12 genes were uniquely upregulated in the clearance group compared to the chronically infected group. Importantly, a number of these 12 genes and their upstream regulators (such as CCL3, IL17D, LBP, SOCS3, NFKBIL1, IRF are associated with innate immune response functions. Conclusions These results suggest that subjects who spontaneously clear HCV may express these unique genes associated with innate immune functions.

  11. Significant association between perceived HIV related stigma and late presentation for HIV/AIDS care in low and middle-income countries: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hailay Abrha Gesesew

    Full Text Available Late presentation for human immunodeficiency virus (HIV care is a major impediment for the success of antiretroviral therapy (ART outcomes. The role that stigma plays as a potential barrier to timely diagnosis and treatment of HIV among people living with HIV/AIDS (acquired immunodeficiency syndrome is ambivalent. This review aimed to assess the best available evidence regarding the association between perceived HIV related stigma and time to present for HIV/AIDS care.Quantitative studies conducted in English language between 2002 and 2016 that evaluated the association between HIV related stigma and late presentation for HIV care were sought across four major databases. This review considered studies that included the following outcome: 'late HIV testing', 'late HIV diagnosis' and 'late presentation for HIV care after testing'. Data were extracted using a standardized Joanna Briggs Institute (JBI data extraction tool. Meta- analysis was undertaken using Revman-5 software. I2 and chi-square test were used to assess heterogeneity. Summary statistics were expressed as pooled odds ratio with 95% confidence intervals and corresponding p-value.Ten studies from low- and middle- income countries met the search criteria, including six (6 and four (4 case control studies and cross-sectional studies respectively. The total sample size in the included studies was 3,788 participants. Half (5 of the studies reported a significant association between stigma and late presentation for HIV care. The meta-analytical association showed that people who perceived high HIV related stigma had two times more probability of late presentation for HIV care than who perceived low stigma (pooled odds ratio = 2.4; 95%CI: 1.6-3.6, I2 = 79%.High perceptions of HIV related stigma influenced timely presentation for HIV care. In order to avoid late HIV care presentation due the fear of stigma among patients, health professionals should play a key role in informing and counselling

  12. Reduced Expression of Siglec-7, NKG2A, and CD57 on Terminally Differentiated CD56-CD16+ Natural Killer Cell Subset Is Associated with Natural Killer Cell Dysfunction in Chronic HIV-1 Clade C Infection.

    Science.gov (United States)

    Zulu, Michael Z; Naidoo, Kewreshini K; Mncube, Zenele; Jaggernath, Manjeetha; Goulder, Philip J R; Ndung'u, Thumbi; Altfeld, Marcus; Thobakgale, Christina F

    2017-12-01

    HIV-1 viremia has been shown to induce several phenotypic and functional abnormalities in natural killer (NK) cells. To assess immune defects associated with HIV viremia, we examined NK cell function, differentiation status, and phenotypic alterations based on expression of inhibitory and activating receptors on NK cells in HIV-1 subtype C chronically infected participants from Durban, South Africa. NK cell phenotypic profiles were characterized by assessing sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7), NKG2A, and NKG2C markers on frozen peripheral blood mononuclear cells from viremic, antiretroviral therapy (ART)-naive HIV-1 chronically infected participants (n = 23), HIV-1 chronically infected participants who had been on combination antiretroviral therapy (cART) for at least 12 months (n = 23) compared with healthy donors (n = 23). NK cell differentiation was assessed by measurement of killer immunoglobulin receptor (KIR) and NKG2A expression; CD57 and CD107a measurements were carried out in HIV viremic and healthy donors. All phenotypic and functional assessments were analyzed by using multicolor flow cytometry. HIV-1-infected participants displayed greater frequencies of the CD56 - CD16 + (CD56negative) NK cell subset compared with healthy donors (p < .0001). Downregulation of Siglec-7 and NKG2A and upregulation of NKG2C were more pronounced in the CD56negative NK cell subset of viremic participants. The CD56negative subset demonstrated a differentiated (KIR + NKG2A - ) phenotype with reduced CD57 expression and lower degranulation capacity in HIV-1-infected participants compared with healthy donors. HIV-1 infection induces the expansion of the CD56negative NK cell subset marked by altered receptor expression profiles that are indicative of impaired function and may explain the overall NK cell dysfunction observed in chronic HIV-1 infection.

  13. HIV-associated neurocognitive disorders

    Directory of Open Access Journals (Sweden)

    Zahir Vally

    2011-12-01

    Full Text Available HIV infection is associated with disturbances in brain function referred to as HIV-associated neurocognitive disorders (HAND. This literature review outlines the recently revised diagnostic criteria for the range of HAND from the earliest to the more advanced stages: (i asymptomatic neurocognitive impairment; (ii mild neurocognitive disorder; and (iii HIV-associated dementia. Relevant literature is also reviewed regarding the differential impact upon component cognitive domains known to be affected in HAND, which in turn should ideally be targeted during clinical and neuropsychological assessments: psychomotor and information processing speed, learning and memory, attention and working memory, speech and language, executive functioning and visuospatial functioning. A discussion outlining the neuropsychological tools used in the diagnostic screening of HAND is also included. The central mechanisms of HAND appear to revolve primarily around psychomotor slowing and cognitive control over mental operations, possibly reflecting the influence of disrupted fronto-striatal circuits on distributed neural networks critical to cognitive functions. The accurate assessment and diagnosis of HAND depends on meeting the need for statistically sound neuropsychological assessment techniques that may be used confidently in assessing South African populations, as well as the development of relevant norms for comparison of test performance data.

  14. HIV Prevalence and Risks Associated with HIV Infection among Transgender Individuals in Cambodia.

    Directory of Open Access Journals (Sweden)

    Amy Weissman

    Full Text Available Recognizing transgender individuals have a high risk of HIV acquisition, and to inform policies and programming, we conducted an HIV prevalence and risk behaviors survey among transgender individuals in Cambodia.Cross-sectional survey using a respondent driven sampling method with self-administered audio-computer assisted interviews. HIV testing was performed prior to the questionnaire with results available immediately after. Eligible participants were ≥18 years, identified as male at birth and self-identified/expressed as a different gender, and reported having sex with at least one male partner in past year. From six major urban centers of Cambodia, 891 transgender individuals were recruited.The majority of the 891 participants self-identified as third gender or female (94.5%, were young (median age 23, IQR [20-27], had secondary education or higher (80.5%, not married (89.7%, and employed (90.2%. The majority had first sex before 18 years (66.8%, with a male (79.9%, 37.9% having been paid or paying for this first sex. The rate of HIV positivity among participants was found to be 4.15%. Consistent condom use with male and female partners was low with all partner types, but particularly low with male partners when paying for sex (20.3%. The majority of participants reported having experienced discrimination in their lifetime (54.8% and 30.3% had been assaulted. Multivariate analysis revealed that older age (adjusted OR = 14.73 [4.20, 51.67] for age 35-44 and adjusted OR = 7.63 [2.55, 22.81] for age 30-34, only having a primary school education or no schooling at all (adjusted OR = 2.62 [1.18, 5.80], being a resident of Siem Reap (adjusted OR = 7.44 [2.37, 23.29], receiving payment at first sex (adjusted OR = 2.26 [1.00, 5.11], having sex during/after using drugs (adjusted OR = 2.90 [1.09, 7.73], inconsistent condom use during last anal sex (adjusted OR = 3.84 [1.58, 9.33], and reporting low self-esteem (adjusted OR = 3.25 [1.35, 7.85] were

  15. Current questions in HIV-associated lung cancer.

    Science.gov (United States)

    Shcherba, Marina; Shuter, Jonathan; Haigentz, Missak

    2013-09-01

    In this review, we explore current questions regarding risk factors contributing to frequent and early onset of lung cancer among populations with HIV infection, treatment, and outcomes of lung cancer in HIV-infected patients as well as challenges in a newly evolving era of lung cancer screening. Lung cancer, seen in three-fold excess in HIV-infected populations, has become the most common non-AIDS defining malignancy in the highly active antiretroviral therapy era. HIV-associated lung cancer appears to be associated with young age at diagnosis, cigarette smoking, advanced stage at presentation, and a more aggressive clinical course. There is no unified explanation for these observations, and aside from traditional risk factors, HIV-related immunosuppression and biological differences might play a role. In addition to smoking cessation interventions, screening and early cancer detection in HIV-infected populations are of high clinical importance, although evidence supporting lung cancer screening in this particularly high-risk subset is currently lacking, as are prospective studies of lung cancer therapy. There is an urgent need for prospective clinical trials in HIV-associated lung cancer to improve understanding of lung cancer pathogenesis and to optimize patient care. Several clinical trials are in progress to address questions in cancer biology, screening, and treatment for this significant cause of mortality in persons with HIV infection.

  16. HIV-1-negative female sex workers sustain high cervical IFNɛ, low immune activation, and low expression of HIV-1-required host genes.

    Science.gov (United States)

    Abdulhaqq, S A; Zorrilla, C; Kang, G; Yin, X; Tamayo, V; Seaton, K E; Joseph, J; Garced, S; Tomaras, G D; Linn, K A; Foulkes, A S; Azzoni, L; VerMilyea, M; Coutifaris, C; Kossenkov, A V; Showe, L; Kraiselburd, E N; Li, Q; Montaner, L J

    2016-07-01

    Sex workers practicing in high HIV endemic areas have been extensively targeted to test anti-HIV prophylactic strategies. We hypothesize that in women with high levels of genital exposure to semen changes in cervico-vaginal mucosal and/or systemic immune activation will contribute to a decreased susceptibility to HIV-1 infection. To address this question, we assessed sexual activity and immune activation status (in peripheral blood), as well as cellular infiltrates and gene expression in ectocervical mucosa biopsies in female sex workers (FSWs; n=50), as compared with control women (CG; n=32). FSWs had low-to-absent HIV-1-specific immune responses with significantly lower CD38 expression on circulating CD4(+) or CD8(+) T-cells (both: PHIV-1 integration and replication. A correlative relationship between semen exposure and elevated type-1 IFN expression in FSWs was also established. Overall, our data suggest that long-term condomless sex work can result in multiple changes within the cervico-vaginal compartment that would contribute to sustaining a lower susceptibility for HIV-1 infection in the absence of HIV-specific responses.

  17. Inefficient HIV-1 trans infection of CD4+ T cells by macrophages from HIV-1 nonprogressors is associated with altered membrane cholesterol and DC-SIGN.

    Science.gov (United States)

    DeLucia, Diana C; Rinaldo, Charles R; Rappocciolo, Giovanna

    2018-04-11

    Professional antigen presenting cells (APC: myeloid dendritic cells (DC) and macrophages (MΦ); B lymphocytes) mediate highly efficient HIV-1 infection of CD4 + T cells, termed trans infection, that could contribute to HIV-1 pathogenesis. We have previously shown that lower cholesterol content in DC and B lymphocytes is associated with a lack of HIV-1 trans infection in HIV-1 infected nonprogressors (NP). Here we assessed whether HIV-1 trans infection mediated by another major APC, MΦ, is deficient in NP due to altered cholesterol metabolism. When comparing healthy HIV-1 seronegatives (SN), rapid progressors (PR), and NP, we found that monocyte-derived MΦ from NP did not mediate HIV-1 trans infection of autologous CD4 + T cells, in contrast to efficient trans infection mediated by SN and PR MΦ. MΦ trans infection efficiency was directly associated with the number of DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)-expressing MΦ. Significantly fewer NP MΦ expressed DC-SIGN. Unesterified (free) cholesterol in MΦ cell membranes and lipid rafting was significantly lower in NP than PR, as well as virus internalization in early endosomes. Furthermore, simvastatin (SIMV), decreased the subpopulation of DC-SIGN + MΦ, as well as MΦ cis and trans infection. Notably, SIMV decreased cell membrane cholesterol and led to lipid raft dissociation, effectively mimicking the incompetent APC trans infection environment characteristic of NP. Our data support that DC-SIGN and membrane cholesterol are central to MΦ trans infection, and a lack of these limits HIV-1 disease progression. Targeting the ability of MΦ to drive HIV-1 dissemination in trans could enhance HIV-1 therapeutic strategies. IMPORTANCE Despite the success of combination anti-retroviral therapy, neither a vaccine nor a cure for HIV infection has been developed, demonstrating a need for novel prophylactic and therapeutic strategies. Here we show that efficiency of macrophage (M

  18. A predominance of R5-like HIV genotypes in vaginal secretions is associated with elevated plasma HIV-1 RNA levels and the absence of anti-retroviral therapy

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    Lacour Nedra

    2008-07-01

    Full Text Available Abstract HIV expressed in genital secretions provides the inoculum from which transmitting variants are selected, both in sexual transmission and mother-to-infant transmission during partuition. Characterization of HIV levels and genotypes found in vaginal secretions and the impact of anti-retroviral therapy (ART on this virus can provide valuable insight for the prevention of HIV transmission. Vaginal HIV was evaluated in a cohort of 43 women attending a New Orleans HIV outpatient clinic. Predominant vaginal genotypes were characterized as R5- or X4-like by heteroduplex tracking analyses of the envelope V3 region. Most women (67.4% shed R5-like genotypes in vaginal secretions which was associated with elevated plasma HIV levels (≥ 10,000 copies HIV-RNA/mL and absence of ART. Because R5-like genotypes are more frequently associated with transmission, these observations suggest that the majority of women shedding HIV in genital secretions present a transmission risk. The levels of vaginal virus were similar between both groups, but shedding of X4-like genotypes was associated with lower plasma viral loads and the use of ART, suggesting that ART use may impact the genotypes of virus found in the female genital compartment.

  19. What's in a Name? AIDS Dementia Complex, HIV-associated ...

    African Journals Online (AJOL)

    Key words: HIV; AIDS; HIV-associated dementia (HAD); HIV-associated neurocognitive disorder (HAND) .... increased survival a mixed picture is becoming more common. ... alternating sequence and memory recall of the four objects.

  20. Cortisol patterns are associated with T cell activation in HIV.

    Directory of Open Access Journals (Sweden)

    Sarah Patterson

    Full Text Available The level of T cell activation in untreated HIV disease is strongly and independently associated with risk of immunologic and clinical progression. The factors that influence the level of activation, however, are not fully defined. Since endogenous glucocorticoids are important in regulating inflammation, we sought to determine whether less optimal diurnal cortisol patterns are associated with greater T cell activation.We studied 128 HIV-infected adults who were not on treatment and had a CD4(+ T cell count above 250 cells/µl. We assessed T cell activation by CD38 expression using flow cytometry, and diurnal cortisol was assessed with salivary measurements.Lower waking cortisol levels correlated with greater T cell immune activation, measured by CD38 mean fluorescent intensity, on CD4(+ T cells (r = -0.26, p = 0.006. Participants with lower waking cortisol also showed a trend toward greater activation on CD8(+ T cells (r = -0.17, p = 0.08. A greater diurnal decline in cortisol, usually considered a healthy pattern, correlated with less CD4(+ (r = 0.24, p = 0.018 and CD8(+ (r = 0.24, p = 0.017 activation.These data suggest that the hypothalamic-pituitary-adrenal (HPA axis contributes to the regulation of T cell activation in HIV. This may represent an important pathway through which psychological states and the HPA axis influence progression of HIV.

  1. Association of HIV diversity and survival in HIV-infected Ugandan infants.

    Directory of Open Access Journals (Sweden)

    Maria M James

    2011-04-01

    Full Text Available The level of viral diversity in an HIV-infected individual can change during the course of HIV infection, reflecting mutagenesis during viral replication and selection of viral variants by immune and other selective pressures. Differences in the level of viral diversity in HIV-infected infants may reflect differences in viral dynamics, immune responses, or other factors that may also influence HIV disease progression. We used a novel high resolution melting (HRM assay to measure HIV diversity in Ugandan infants and examined the relationship between diversity and survival through 5 years of age.Plasma samples were obtained from 31 HIV-infected infants (HIVNET 012 trial. The HRM assay was used to measure diversity in two regions in the gag gene (Gag1 and Gag2 and one region in the pol gene (Pol.HRM scores in all three regions increased with age from 6-8 weeks to 12-18 months (for Gag1: P = 0.005; for Gag2: P = 0.006; for Pol: P = 0.016. Higher HRM scores at 6-8 weeks of age (scores above the 75(th percentile were associated with an increased risk of death by 5 years of age (for Pol: P = 0.005; for Gag1/Gag2 (mean of two scores: P = 0.003; for Gag1/Gag2/Pol (mean of three scores: P = 0.002. We did not find an association between HRM scores and other clinical and laboratory variables.Genetic diversity in HIV gag and pol measured using the HRM assay was typically low near birth and increased over time. Higher HIV diversity in these regions at 6-8 weeks of age was associated with a significantly increased risk of death by 5 years of age.

  2. Mechanisms Underlying HIV-Associated Noninfectious Lung Disease.

    Science.gov (United States)

    Presti, Rachel M; Flores, Sonia C; Palmer, Brent E; Atkinson, Jeffrey J; Lesko, Catherine R; Lau, Bryan; Fontenot, Andrew P; Roman, Jesse; McDyer, John F; Twigg, Homer L

    2017-11-01

    Pulmonary disease remains a primary source of morbidity and mortality in persons living with HIV (PLWH), although the advent of potent combination antiretroviral therapy has resulted in a shift from predominantly infectious to noninfectious pulmonary complications. PLWH are at high risk for COPD, pulmonary hypertension, and lung cancer even in the era of combination antiretroviral therapy. The underlying mechanisms of this are incompletely understood, but recent research in both human and animal models suggests that oxidative stress, expression of matrix metalloproteinases, and genetic instability may result in lung damage, which predisposes PLWH to these conditions. Some of the factors that drive these processes include tobacco and other substance use, direct HIV infection and expression of specific HIV proteins, inflammation, and shifts in the microbiome toward pathogenic and opportunistic organisms. Further studies are needed to understand the relative importance of these factors to the development of lung disease in PLWH. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  3. MR brain volumetric measurements are predictive of neurobehavioral impairment in the HIV-1 transgenic rat.

    Science.gov (United States)

    Casas, Rafael; Muthusamy, Siva; Wakim, Paul G; Sinharay, Sanhita; Lentz, Margaret R; Reid, William C; Hammoud, Dima A

    2018-01-01

    HIV infection is known to be associated with brain volume loss, even in optimally treated patients. In this study, we assessed whether dynamic brain volume changes over time are predictive of neurobehavorial performance in the HIV-1 transgenic (Tg) rat, a model of treated HIV-positive patients. Cross-sectional brain MRI imaging was first performed comparing Tg and wild type (WT) rats at 3 and 19 months of age. Longitudinal MRI and neurobehavioral testing of another group of Tg and WT rats was then performed from 5 to 23 weeks of age. Whole brain and subregional image segmentation was used to assess the rate of brain growth over time. We used repeated-measures mixed models to assess differences in brain volumes and to establish how predictive the volume differences are of specific neurobehavioral deficits. Cross-sectional imaging showed smaller whole brain volumes in Tg compared to WT rats at 3 and at 19 months of age. Longitudinally, Tg brain volumes were smaller than age-matched WT rats at all time points, starting as early as 5 weeks of age. The Tg striatal growth rate delay between 5 and 9 weeks of age was greater than that of the whole brain. Striatal volume in combination with genotype was the most predictive of rota-rod scores and in combination with genotype and age was the most predictive of total exploratory activity scores in the Tg rats. The disproportionately delayed striatal growth compared to whole brain between 5 and 9 weeks of age and the role of striatal volume in predicting neurobehavioral deficits suggest an important role of the dopaminergic system in HIV associated neuropathology. This might explain problems with motor coordination and executive decisions in this animal model. Smaller brain and subregional volumes and neurobehavioral deficits were seen as early as 5 weeks of age, suggesting an early brain insult in the Tg rat. Neuroprotective therapy testing in this model should thus target this early stage of development, before brain

  4. Predictive Validity And Usefulness Of Visual Scanning Task In Hiv ...

    African Journals Online (AJOL)

    The visual scanning task is a useful screening tool for brain damage in HIV/AIDS by inference from impairment of visual information processing and disturbances in perceptual mental strategies. There is progressive neuro-cognitive decline as the disease worsens. Keywords: brain, cognition, HIV/AIDS, predictive validity, ...

  5. Unchanged Levels of Soluble CD14 and IL-6 Over Time Predict Serious Non-AIDS Events in HIV-1-Infected People

    Science.gov (United States)

    Sunil, Meena; Nigalye, Maitreyee; Somasunderam, Anoma; Martinez, Maria Laura; Yu, Xiaoying; Arduino, Roberto C.; Bell, Tanvir K.

    2016-01-01

    Abstract HIV-1-infected persons have increased risk of serious non-AIDS events (SNAEs) despite suppressive antiretroviral therapy. Increased circulating levels of soluble CD14 (sCD14), soluble CD163 (sCD163), and interleukin-6 (IL-6) at a single time point have been associated with SNAEs. However, whether changes in these biomarker levels predict SNAEs in HIV-1-infected persons is unknown. We hypothesized that greater decreases in inflammatory biomarkers would be associated with fewer SNAEs. We identified 39 patients with SNAEs, including major cardiovascular events, end stage renal disease, decompensated cirrhosis, non-AIDS-defining malignancies, and death of unknown cause, and age- and sex-matched HIV-1-infected controls. sCD14, sCD163, and IL-6 were measured at study enrollment (T1) and proximal to the event (T2) or equivalent duration in matched controls. Over ∼34 months, unchanged rather than decreasing levels of sCD14 and IL-6 predicted SNAEs. Older age and current illicit substance abuse, but not HCV coinfection, were associated with SNAEs. In a multivariate analysis, older age, illicit substance use, and unchanged IL-6 levels remained significantly associated with SNAEs. Thus, the trajectories of sCD14 and IL-6 levels predict SNAEs. Interventions to decrease illicit substance use may decrease the risk of SNAEs in HIV-1-infected persons. PMID:27344921

  6. Expression of affordable microbicides to combat the spread of HIV pandemic

    CSIR Research Space (South Africa)

    Mawela, K

    2010-09-01

    Full Text Available activation, normal T expressed and secreted) show anti-HIV activity through their ability to block the HIV coreceptor CCR5 (Figure 1), and a number of N-terminally modified analogues of these proteins with much higher antiviral potency have been developed...

  7. Increased CD56(bright) NK cells in HIV-HCV co-infection and HCV mono-infection are associated with distinctive alterations of their phenotype.

    Science.gov (United States)

    Bhardwaj, Suvercha; Ahmad, Fareed; Wedemeyer, Heiner; Cornberg, Marcus; Schulze Zur Wiesch, Julian; van Lunzen, Jan; Sarin, Shiv K; Schmidt, Reinhold E; Meyer-Olson, Dirk

    2016-04-18

    HIV-HCV co-infection is associated with accelerated progression to hepatic fibrosis, cirrhosis and hepatocellular carcinoma than HCV mono-infection. The contribution of innate immunity during HIV-HCV co-infection has been a relatively under-investigated area. Natural killer (NK) cells are pivotal sentinels of innate immunity against viruses and tumour cells. In this study we evaluated the effect of HIV-HCV co-infection on peripheral blood NK cell subsets with emphasis on the phenotype of CD56(bright) NK cells. Sixty patients were included in the study; HIV mono-infected (n = 12), HCV mono-infected (n = 15), HCV-HIV co-infected (n = 21) and healthy controls (n = 16). PBMCs were isolated and immunophenotyping of NK cells was performed by flowcytometry. We observed an expansion of CD56(bright) NK cell subset in HIV-HCV co-infection as compared to healthy controls and HIV mono-infected group. All the infected groups had an upregulated expression of the activating receptor NKG2D on CD56(bright) NK cells in comparison to healthy controls while not differing amongst themselves. The expression of NKp46 in HIV-HCV co-infected group was significantly upregulated as compared to both HIV as well as HCV mono-infections while NKp30 expression in the HIV-HCV co-infected group significantly differed as compared to HIV mono-infection. The CD56(bright) NK cell subset was activated in HIV-HCV co-infection as assessed by the expression of CD69 as compared to healthy controls but was significantly downregulated in comparison to HIV mono-infection. CD95 expression on CD56(bright) NK cells followed the same pattern where there was an increased expression of CD95 in HIV mono-infection and HIV-HCV co-infection as compared to healthy controls. In contrast to CD69 expression, CD95 expression in HCV mono-infection was decreased when compared to HIV mono-infection and HIV-HCV co-infection. Finally, expression of CXCR3 on CD56(bright) NK cells was increased in HIV-HCV co-infection in comparison

  8. Cloning, Expression and Purification of the Recombinant HIV-1 Tat-Nef Fusion Protein in Prokaryotic Expression System

    OpenAIRE

    Somayeh Kadkhodayan; Shiva Irani; Seyed Mehdi Sadat; Fatemeh Fotouhi; Azam Bolhassani

    2016-01-01

    Abstract Background: Nef is one of the HIV-1 critical proteins, because it is essential for viral replication and AIDS disease progression and induction of immune response against it can partially inhibit viral infection. Moreover, a domain of the HIV-1 Trans-Activator of Transcription (Tat, 48-60 aa) could act as a cell penetrating peptide (CPP). In current study, cloning and expression of Tat-Nef fusion protein was performed in E. coli for the first time. The protein expression was confi...

  9. Design and expression of a short peptide as an HIV detection probe

    Energy Technology Data Exchange (ETDEWEB)

    Lines, Jamie A.; Yu, Zhiqiang; Dedkova, Larisa M.; Chen, Shengxi, E-mail: shengxi.chen.1@asu.edu

    2014-01-03

    Highlights: •We designed a short fusion peptide (FP-50) for in vivo expression. •This peptide is a very promising component for detection of gp120 protein. •The detectable level is about 20–200 times lower than previously published methods. •It is a novel probe to detect HIV-1 gp120 during early stages of HIV infection. -- Abstract: To explore a low-cost novel probe for HIV detection, we designed and prepared a 50-amino acid-length short fusion peptide (FP-50) via Escherichia coli in vivo expression. It was employed as a novel probe to detect HIV-1 gp120 protein. The detectable level of gp120 protein using the FP-50 peptide was approximately 20–200 times lower than previously published methods that used a pair of monoclonal antibodies. Thus, this short peptide is a very promising component for detection of gp120 protein during early stages of HIV infection.

  10. Predicting substance abuse among youth with, or at high risk for, HIV

    NARCIS (Netherlands)

    Huba, GJ; Melchoir, LA; Greenberg, B; Trevithick, L; Feudo, R; Tierney, S; Sturdevant, M; Hodgins, A; Remafedi, G; Woods, ER; Wallace, M; Schneir, A; Kawata, AK; Brady, RE; Singer, B; Marconi, K; Wright, E; Panter, AT

    This article describes data from 4,111 males and 4,085 females participating in 10 HIV/AIDS service demonstration projects. The sample was diverse in age, gender, ethnicity, HIV status, and risk for HIV transmission. Logistic regression was used to determine the attributes that best predict

  11. High level of soluble HLA-G in the female genital tract of Beninese commercial sex workers is associated with HIV-1 infection.

    Science.gov (United States)

    Thibodeau, Valérie; Lajoie, Julie; Labbé, Annie-Claude; Zannou, Marcel D; Fowke, Keith R; Alary, Michel; Poudrier, Johanne; Roger, Michel

    2011-01-01

    Most HIV infections are transmitted across mucosal epithelium. Understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, are of fundamental importance. HLA-G is a powerful modulator of the immune response. The aim of this study was to investigate whether soluble HLA-G (sHLA-G) expression in the female genital tract is associated with HIV-1 infection. Genital levels of sHLA-G were determined in 52 HIV-1-uninfected and 44 antiretroviral naïve HIV-1-infected female commercial sex workers (CSWs), as well as 71 HIV-1-uninfected non-CSW women at low risk of exposure, recruited in Cotonou, Benin. HIV-1-infected CSWs had higher genital levels of sHLA-G compared with those in both the HIV-1-uninfected CSW (P = 0.009) and non-CSW groups (P = 0.0006). The presence of bacterial vaginosis (P = 0.008), and HLA-G*01:01:02 genotype (P = 0.002) were associated with higher genital levels of sHLA-G in the HIV-1-infected CSWs, whereas the HLA-G*01:04:04 genotype was also associated with higher genital level of sHLA-G in the overall population (P = 0.038). When adjustment was made for all significant variables, the increased expression of sHLA-G in the genital mucosa remained significantly associated with both HIV-1 infection (P = 0.02) and bacterial vaginosis (P = 0.03). This study demonstrates that high level of sHLA-G in the genital mucosa is independently associated with both HIV-1 infection and bacterial vaginosis.

  12. Dual-mixed HIV-1 coreceptor tropism and HIV-associated neurocognitive deficits.

    Science.gov (United States)

    Morris, Sheldon R; Woods, Steven Paul; Deutsch, Reena; Little, Susan J; Wagner, Gabriel; Morgan, Erin E; Heaton, Robert K; Letendre, Scott L; Grant, Igor; Smith, Davey M

    2013-10-01

    HIV coreceptor usage of CXCR4 (X4) is associated with decreased CD4+ T-cell counts and accelerated disease progression, but the role of X4 tropism in HIV-associated neurocognitive disorders (HAND) has not previously been described. This longitudinal study evaluated data on 197 visits from 72 recently HIV-infected persons who had undergone up to four sequential neurocognitive assessments over a median of 160 days (IQR, 138–192). Phenotypic tropism testing (Trofile ES, Monogram, Biosciences) was performed on stored blood samples. Multivariable mixed model repeated measures regression was used to determine the association between HAND and dual-mixed (DM) viral tropism, estimated duration of infection (EDI), HIV RNA, CD4 count, and problematic methamphetamine use. Six subjects (8.3 %) had DM at their first neurocognitive assessment and four converted to DM in subsequent sampling (for total of 10 DM) at a median EDI of 10.1 months (IQR, 7.2–12.2). There were 44 (61.1 %) subjects who demonstrated HAND on at least one study visit. HAND was associated with DM tropism (odds ratio, 4.4; 95 % CI, 0.9–20.5) and shorter EDI (odds ratio 1.1 per month earlier; 95 % CI, 1.0–1.2). This study found that recency of HIV-1 infection and the development of DM tropism may be associated with HAND in the relatively early stage of infection. Together, these data suggest that viral interaction with cellular receptors may play an important role in the early manifestation of HAND.

  13. HIV-1 with multiple CCR5/CXCR4 chimeric receptor use is predictive of immunological failure in infected children.

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    Mariangela Cavarelli

    Full Text Available BACKGROUND: HIV-1 R5 viruses are characterized by a large phenotypic variation, that is reflected by the mode of coreceptor use. The ability of R5 HIV-1 to infect target cells expressing chimeric receptors between CCR5 and CXCR4 (R5(broad viruses, was shown to correlate with disease stage in HIV-1 infected adults. Here, we ask the question whether phenotypic variation of R5 viruses could play a role also in mother-to-child transmission (MTCT of HIV-1 and pediatric disease progression. METHODOLOGY/PRINCIPAL FINDINGS: Viral isolates obtained from a total of 59 HIV-1 seropositive women (24 transmitting and 35 non transmitting and 28 infected newborn children, were used to infect U87.CD4 cells expressing wild type or six different CCR5/CXCR4 chimeric receptors. HIV-1 isolates obtained from newborn infants had predominantly R5(narrow phenotype (n = 20, but R5(broad and R5X4 viruses were also found in seven and one case, respectively. The presence of R5(broad and R5X4 phenotypes correlated significantly with a severe decline of the CD4+ T cells (CDC stage 3 or death within 2 years of age. Forty-three percent of the maternal R5 isolates displayed an R5(broad phenotype, however, the presence of the R5(broad virus was not predictive for MTCT of HIV-1. Of interest, while only 1 of 5 mothers with an R5X4 virus transmitted the dualtropic virus, 5 of 6 mothers carrying R5(broad viruses transmitted viruses with a similar broad chimeric coreceptor usage. Thus, the maternal R5(broad phenotype was largely preserved during transmission and could be predictive of the phenotype of the newborn's viral variant. CONCLUSIONS/SIGNIFICANCE: Our results show that R5(broad viruses are not hampered in transmission. When transmitted, immunological failure occurs earlier than in children infected with HIV-1 of R5(narrow phenotype. We believe that this finding is of utmost relevance for therapeutic interventions in pediatric HIV-1 infection.

  14. Clinicopathologic and gene expression parameters predict liver cancer prognosis

    International Nuclear Information System (INIS)

    Hao, Ke; Zhong, Hua; Greenawalt, Danielle; Ferguson, Mark D; Ng, Irene O; Sham, Pak C; Poon, Ronnie T; Molony, Cliona; Schadt, Eric E; Dai, Hongyue; Luk, John M; Lamb, John; Zhang, Chunsheng; Xie, Tao; Wang, Kai; Zhang, Bin; Chudin, Eugene; Lee, Nikki P; Mao, Mao

    2011-01-01

    The prognosis of hepatocellular carcinoma (HCC) varies following surgical resection and the large variation remains largely unexplained. Studies have revealed the ability of clinicopathologic parameters and gene expression to predict HCC prognosis. However, there has been little systematic effort to compare the performance of these two types of predictors or combine them in a comprehensive model. Tumor and adjacent non-tumor liver tissues were collected from 272 ethnic Chinese HCC patients who received curative surgery. We combined clinicopathologic parameters and gene expression data (from both tissue types) in predicting HCC prognosis. Cross-validation and independent studies were employed to assess prediction. HCC prognosis was significantly associated with six clinicopathologic parameters, which can partition the patients into good- and poor-prognosis groups. Within each group, gene expression data further divide patients into distinct prognostic subgroups. Our predictive genes significantly overlap with previously published gene sets predictive of prognosis. Moreover, the predictive genes were enriched for genes that underwent normal-to-tumor gene network transformation. Previously documented liver eSNPs underlying the HCC predictive gene signatures were enriched for SNPs that associated with HCC prognosis, providing support that these genes are involved in key processes of tumorigenesis. When applied individually, clinicopathologic parameters and gene expression offered similar predictive power for HCC prognosis. In contrast, a combination of the two types of data dramatically improved the power to predict HCC prognosis. Our results also provided a framework for understanding the impact of gene expression on the processes of tumorigenesis and clinical outcome

  15. Metabolically active CD4+ T cells expressing Glut1 and OX40 preferentially harbor HIV during in vitro infection.

    Science.gov (United States)

    Palmer, Clovis S; Duette, Gabriel A; Wagner, Marc C E; Henstridge, Darren C; Saleh, Suah; Pereira, Candida; Zhou, Jingling; Simar, David; Lewin, Sharon R; Ostrowski, Matias; McCune, Joseph M; Crowe, Suzanne M

    2017-10-01

    High glucose transporter 1 (Glut1) surface expression is associated with increased glycolytic activity in activated CD4+ T cells. Phosphatidylinositide 3-kinases (PI3K) activation measured by p-Akt and OX40 is elevated in CD4+Glut1+ T cells from HIV+ subjects. TCR engagement of CD4+Glut1+ T cells from HIV+ subjects demonstrates hyperresponsive PI3K-mammalian target of rapamycin signaling. High basal Glut1 and OX40 on CD4+ T cells from combination antiretroviral therapy (cART)-treated HIV+ patients represent a sufficiently metabolically active state permissive for HIV infection in vitro without external stimuli. The majority of CD4+OX40+ T cells express Glut1, thus OX40 rather than Glut1 itself may facilitate HIV infection. Furthermore, infection of CD4+ T cells is limited by p110γ PI3K inhibition. Modulating glucose metabolism may limit cellular activation and prevent residual HIV replication in 'virologically suppressed' cART-treated HIV+ persons. © 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  16. Identification of Genes Whose Expression Profile Is Associated with Non-Progression towards AIDS Using eQTLs

    Science.gov (United States)

    Le Clerc, Sigrid; van Manen, Daniëlle; Coulonges, Cédric; Ulveling, Damien; Laville, Vincent; Labib, Taoufik; Taing, Lieng; Delaneau, Olivier; Montes, Matthieu; Schuitemaker, Hanneke; Zagury, Jean-François

    2015-01-01

    Background Many genome-wide association studies have been performed on progression towards the acquired immune deficiency syndrome (AIDS) and they mainly identified associations within the HLA loci. In this study, we demonstrate that the integration of biological information, namely gene expression data, can enhance the sensitivity of genetic studies to unravel new genetic associations relevant to AIDS. Methods We collated the biological information compiled from three databases of expression quantitative trait loci (eQTLs) involved in cells of the immune system. We derived a list of single nucleotide polymorphisms (SNPs) that are functional in that they correlate with differential expression of genes in at least two of the databases. We tested the association of those SNPs with AIDS progression in two cohorts, GRIV and ACS. Tests on permuted phenotypes of the GRIV and ACS cohorts or on randomised sets of equivalent SNPs allowed us to assess the statistical robustness of this method and to estimate the true positive rate. Results Eight genes were identified with high confidence (p = 0.001, rate of true positives 75%). Some of those genes had previously been linked with HIV infection. Notably, ENTPD4 belongs to the same family as CD39, whose expression has already been associated with AIDS progression; while DNAJB12 is part of the HSP90 pathway, which is involved in the control of HIV latency. Our study also drew our attention to lesser-known functions such as mitochondrial ribosomal proteins and a zinc finger protein, ZFP57, which could be central to the effectiveness of HIV infection. Interestingly, for six out of those eight genes, down-regulation is associated with non-progression, which makes them appealing targets to develop drugs against HIV. PMID:26367535

  17. Identification of Genes Whose Expression Profile Is Associated with Non-Progression towards AIDS Using eQTLs.

    Directory of Open Access Journals (Sweden)

    Jean-Louis Spadoni

    Full Text Available Many genome-wide association studies have been performed on progression towards the acquired immune deficiency syndrome (AIDS and they mainly identified associations within the HLA loci. In this study, we demonstrate that the integration of biological information, namely gene expression data, can enhance the sensitivity of genetic studies to unravel new genetic associations relevant to AIDS.We collated the biological information compiled from three databases of expression quantitative trait loci (eQTLs involved in cells of the immune system. We derived a list of single nucleotide polymorphisms (SNPs that are functional in that they correlate with differential expression of genes in at least two of the databases. We tested the association of those SNPs with AIDS progression in two cohorts, GRIV and ACS. Tests on permuted phenotypes of the GRIV and ACS cohorts or on randomised sets of equivalent SNPs allowed us to assess the statistical robustness of this method and to estimate the true positive rate.Eight genes were identified with high confidence (p = 0.001, rate of true positives 75%. Some of those genes had previously been linked with HIV infection. Notably, ENTPD4 belongs to the same family as CD39, whose expression has already been associated with AIDS progression; while DNAJB12 is part of the HSP90 pathway, which is involved in the control of HIV latency. Our study also drew our attention to lesser-known functions such as mitochondrial ribosomal proteins and a zinc finger protein, ZFP57, which could be central to the effectiveness of HIV infection. Interestingly, for six out of those eight genes, down-regulation is associated with non-progression, which makes them appealing targets to develop drugs against HIV.

  18. In situ aromatase expression in primary tumor is associated with estrogen receptor expression but is not predictive of response to endocrine therapy in advanced breast cancer

    International Nuclear Information System (INIS)

    Lykkesfeldt, Anne E; Henriksen, Katrine L; Rasmussen, Birgitte B; Sasano, Hironobu; Evans, Dean B; Møller, Susanne; Ejlertsen, Bent; Mouridsen, Henning T

    2009-01-01

    New, third-generation aromatase inhibitors (AIs) have proven comparable or superior to the anti-estrogen tamoxifen for treatment of estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer. AIs suppress total body and intratumoral estrogen levels. It is unclear whether in situ carcinoma cell aromatization is the primary source of estrogen production for tumor growth and whether the aromatase expression is predictive of response to endocrine therapy. Due to methodological difficulties in the determination of the aromatase protein, COX-2, an enzyme involved in the synthesis of aromatase, has been suggested as a surrogate marker for aromatase expression. Primary tumor material was retrospectively collected from 88 patients who participated in a randomized clinical trial comparing the AI letrozole to the anti-estrogen tamoxifen for first-line treatment of advanced breast cancer. Semi-quantitative immunohistochemical (IHC) analysis was performed for ER, PR, COX-2 and aromatase using Tissue Microarrays (TMAs). Aromatase was also analyzed using whole sections (WS). Kappa analysis was applied to compare association of protein expression levels. Univariate Wilcoxon analysis and the Cox-analysis were performed to evaluate time to progression (TTP) in relation to marker expression. Aromatase expression was associated with ER, but not with PR or COX-2 expression in carcinoma cells. Measurements of aromatase in WS were not comparable to results from TMAs. Expression of COX-2 and aromatase did not predict response to endocrine therapy. Aromatase in combination with high PR expression may select letrozole treated patients with a longer TTP. TMAs are not suitable for IHC analysis of in situ aromatase expression and we did not find COX-2 expression in carcinoma cells to be a surrogate marker for aromatase. In situ aromatase expression in tumor cells is associated with ER expression and may thus point towards good prognosis. Aromatase expression in cancer

  19. Secretory leukocyte protease inhibitor expression and high-risk HPV infection in anal lesions of HIV positive patients

    Science.gov (United States)

    NUOVO, Gerard J.; GRINSZTEJN, Beatriz; FRIEDMAN, Ruth K.; VELOSO, Valdiléa G.; CUNHA, Cynthia B.; COUTINHO, José R.; VIANNA-ANDRADE, Cecilia; OLIVEIRA, Nathalia S.; WOODHAM, Andrew W.; DA SILVA, Diane M.; KAST, W. Martin

    2016-01-01

    Objective The aim of the current study was to evaluate secretory leukocyte protease inhibitor (SLPI) expression in anal biopsies from HIV-positive (HIV+) individuals, and compare that to anal intraepithelial neoplasia (AIN) diagnoses and human papillomavirus (HPV) status. Design This is a cross-sectional study of a cohort of 54 HIV+ (31 males and 23 females) from an AIDS clinic in Rio de Janeiro, Brazil. Methods The study material consisted of anorectal tissue biopsies obtained from HIV+ subjects, which were used to construct tissue microarray paraffin blocks for immunohistochemical analysis of SLPI expression. Biopsies were evaluated by an expert pathologist and classified as low-grade anal intraepithelial neoplasia (AIN1), high-grade anal intraepithelial neoplasia (AIN2/3), or normal squamous epithelium. Additionally, DNA from the biopsies was extracted and analyzed for the presence of low- or high-risk HPV DNA. Results Histologically normal squamous epithelium from the anorectal region showed strong positive SLPI staining in 17/20 (85%) samples. In comparison, 9/17 (53%) dysplastic squamous epithelial samples from AIN1 patients showed strong SLPI staining, and only 5/17 (29%) samples from AIN2-3 patients exhibited strong SPLI staining, which both were significantly fewer than those from normal tissue (p=0.005). Furthermore, there was a significantly higher proportion of samples in which oncogenic high-risk HPV genotypes were detected in low SLPI expressing tissues than that in tissues with high SLPI expression (p=0.040). Conclusion Taken together these results suggest that low SLPI expression is associated with high-risk HPV infections in the development of AIN. PMID:27149102

  20. Research progress of HIV-associated myelopathy

    Directory of Open Access Journals (Sweden)

    Kun HONG

    2016-08-01

    Full Text Available The wide usage of highly active antiretroviral therapy (HAART leads to reduction of the occurence rate of focal or diffuse neurological damage caused by human immunodeficiency virus (HIV infection, which prominently improves the living quality of HIV-infected patients. Despite this progress, about 70% of HIV-infected patients develop neurological complications. Although neurological disease typically occurs in the advanced stage of the disease or after severe damage of immune functions, it may also occur during early stage of the infection. HIV-associated myelopathy is a common complication of immunodeficiency syndrome and its typical pathological appearence is vacuolar degeneration. In many patients the clinical manifestations of vacuolar myelopathy are in fact limited to non-specific sphincter or sexual dysfunction, and may remain completely asymptomatic. Even when motor and sensory symptoms become evident, the diagnosis is often complicated by a concomitant peripheral neuropathy. The purpose of this study is to summarize pathogenesis, clinical manifestations, pathological features, diagnosis and treatment of HIV-associated myelopathy. DOI: 10.3969/j.issn.1672-6731.2016.08.004

  1. Significant association between perceived HIV related stigma and late presentation for HIV/AIDS care in low and middle-income countries: A systematic review and meta-analysis

    Science.gov (United States)

    Gesesew, Hailay Abrha; Tesfay Gebremedhin, Amanuel; Demissie, Tariku Dejene; Kerie, Mirkuzie Woldie; Sudhakar, Morankar; Mwanri, Lillian

    2017-01-01

    Background Late presentation for human immunodeficiency virus (HIV) care is a major impediment for the success of antiretroviral therapy (ART) outcomes. The role that stigma plays as a potential barrier to timely diagnosis and treatment of HIV among people living with HIV/AIDS (acquired immunodeficiency syndrome) is ambivalent. This review aimed to assess the best available evidence regarding the association between perceived HIV related stigma and time to present for HIV/AIDS care. Methods Quantitative studies conducted in English language between 2002 and 2016 that evaluated the association between HIV related stigma and late presentation for HIV care were sought across four major databases. This review considered studies that included the following outcome: ‘late HIV testing’, ‘late HIV diagnosis’ and ‘late presentation for HIV care after testing’. Data were extracted using a standardized Joanna Briggs Institute (JBI) data extraction tool. Meta- analysis was undertaken using Revman-5 software. I2 and chi-square test were used to assess heterogeneity. Summary statistics were expressed as pooled odds ratio with 95% confidence intervals and corresponding p-value. Results Ten studies from low- and middle- income countries met the search criteria, including six (6) and four (4) case control studies and cross-sectional studies respectively. The total sample size in the included studies was 3,788 participants. Half (5) of the studies reported a significant association between stigma and late presentation for HIV care. The meta-analytical association showed that people who perceived high HIV related stigma had two times more probability of late presentation for HIV care than who perceived low stigma (pooled odds ratio = 2.4; 95%CI: 1.6–3.6, I2 = 79%). Conclusions High perceptions of HIV related stigma influenced timely presentation for HIV care. In order to avoid late HIV care presentation due the fear of stigma among patients, health professionals should

  2. Motor function declines over time in human immunodeficiency virus and is associated with cerebrovascular disease, while HIV-associated neurocognitive disorder remains stable.

    Science.gov (United States)

    M Elicer, Isabel; Byrd, Desiree; Clark, Uraina S; Morgello, Susan; Robinson-Papp, Jessica

    2018-04-25

    HIV-associated neurocognitive disorders (HAND) remain prevalent in the combined antiretroviral therapy (CART) era, especially the milder forms. Despite these milder phenotypes, we have shown that motor abnormalities persist and have quantified them with the HIV Dementia Motor Scale (HDMS). Our objectives were to replicate, in an independent sample, our prior findings that the HDMS is associated with cognitive impairment in HIV, while adding consideration of age-associated comorbidities such as cerebrovascular disease, and to examine the longitudinal trajectories of cognitive and motor dysfunction. We included all participants enrolled in the Manhattan HIV Brain Bank (MHBB) from January 2007 to May 2017 who had complete baseline data (N = 164). MHBB participants undergo standardized longitudinal assessments including documentation of comorbidities and medications, blood work, the HDMS, and neurocognitive testing. We found that motor dysfunction, cognitive impairment, and cerebrovascular disease were significantly associated with each other at baseline. Cerebrovascular disease independently predicted cognitive impairment in a multivariable model. Longitudinal analysis in a subset of 78 participants with ≥ 4 years of follow-up showed a stable cognition but declining motor function. We conclude that the HDMS is a valid measurement of motor dysfunction in HIV-infected patients and is associated with cognitive impairment and the presence of cerebrovascular disease. Cognitive impairment is mild and stable in CART-treated HIV; however, motor function declines over time, which may be related to the accrual of comorbidities such as cerebrovascular disease. Further research should examine the mechanisms underlying motor dysfunction in HIV and its clinical impact.

  3. Early initiation of highly active antiretroviral therapy fails to reverse immunovirological abnormalities in gut-associated lymphoid tissue induced by acute HIV infection.

    Science.gov (United States)

    Tincati, Camilla; Biasin, Mara; Bandera, Alessandra; Violin, Michela; Marchetti, Giulia; Piacentini, Luca; Vago, Gian Luca; Balotta, Claudia; Moroni, Mauro; Franzetti, Fabio; Clerici, Mario; Gori, Andrea

    2009-01-01

    During the acute phase of HIV infection, large CD4+ T-cell depletion occurs in the gastrointestinal tract. The kinetics of CD4+ T-cell decrease and highly active antiretroviral therapy (HAART)-mediated immune reconstitution were evaluated. Rectosigmoid colonic (RSC) biopsies and blood samples of nine patients with acute HIV infection were collected. CD4+ T-cell count, HIV RNA, intracellular HIV DNA and messenger RNA cytokine expression were evaluated before and after 6 months of HAART. All nine patients presented symptomatic retroviral infection. Early HAART was associated with a sustained and comparable reduction of HIV RNA in plasma, peripheral blood mononuclear cells (PBMCs) and RSC biopsies. HIV DNA decreased in PBMCs, but was only marginally reduced in RSC biopsies. Comparisons between reduction rates of HIV DNA in these two compartments confirmed that HIV DNA clearance was less efficient in RSC biopsies compared with PBMCs. Assessment of immunological profiles in PBMCs and RSC biopsies showed that the T-helper (Th)1-like/Th2-like ratio was sharply decreased in RSC biopsies and increased in PBMCs throughout the study period. A persistent Th2-like profile was detected in RSC biopsies. Efficient clearing of HIV DNA observed in PBMCs correlated with the establishment of a more favourable Th1-like profile. A less efficient clearance of intracellular HIV DNA following early introduction of HAART is associated with persistent immunological impairment in gut-associated lymphoid tissue (GALT), which is reflected by the skewed expression of cytokines in this reservoir. The present study shows that early initiation of HAART, in the short-term, is not effective in containing the establishment of HIV infection and in reversing associated immunological GALT abnormalities.

  4. Increased CDK5 expression in HIV encephalitis contributes to neurodegeneration via tau phosphorylation and is reversed with Roscovitine.

    Science.gov (United States)

    Patrick, Christina; Crews, Leslie; Desplats, Paula; Dumaop, Wilmar; Rockenstein, Edward; Achim, Cristian L; Everall, Ian P; Masliah, Eliezer

    2011-04-01

    Recent treatments with highly active antiretroviral therapy (HAART) regimens have been shown to improve general clinical status in patients with human immunodeficiency virus (HIV) infection; however, the prevalence of cognitive alterations and neurodegeneration has remained the same or has increased. These deficits are more pronounced in the subset of HIV patients with the inflammatory condition known as HIV encephalitis (HIVE). Activation of signaling pathways such as GSK3β and CDK5 has been implicated in the mechanisms of HIV neurotoxicity; however, the downstream mediators of these effects are unclear. The present study investigated the involvement of CDK5 and tau phosphorylation in the mechanisms of neurodegeneration in HIVE. In the frontal cortex of patients with HIVE, increased levels of CDK5 and p35 expression were associated with abnormal tau phosphorylation. Similarly, transgenic mice engineered to express the HIV protein gp120 exhibited increased brain levels of CDK5 and p35, alterations in tau phosphorylation, and dendritic degeneration. In contrast, genetic knockdown of CDK5 or treatment with the CDK5 inhibitor roscovitine improved behavioral performance in the water maze test and reduced neurodegeneration, abnormal tau phosphorylation, and astrogliosis in gp120 transgenic mice. These findings indicate that abnormal CDK5 activation contributes to the neurodegenerative process in HIVE via abnormal tau phosphorylation; thus, reducing CDK5 might ameliorate the cognitive impairments associated with HIVE. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  5. CCR5 Gene Disruption via Lentiviral Vectors Expressing Cas9 and Single Guided RNA Renders Cells Resistant to HIV-1 Infection

    Science.gov (United States)

    Liu, Jingjing; Zhang, Di; Kimata, Jason T.; Zhou, Paul

    2014-01-01

    CCR5, a coreceptor for HIV-1 entry, is a major target for drug and genetic intervention against HIV-1. Genetic intervention strategies have knocked down CCR5 expression levels by shRNA or disrupted the CCR5 gene using zinc finger nucleases (ZFN) or Transcription activator-like effector nuclease (TALEN). In the present study, we silenced CCR5 via CRISPR associated protein 9 (Cas9) and single guided RNAs (sgRNAs). We constructed lentiviral vectors expressing Cas9 and CCR5 sgRNAs. We show that a single round transduction of lentiviral vectors expressing Cas9 and CCR5 sgRNAs into HIV-1 susceptible human CD4+ cells yields high frequencies of CCR5 gene disruption. CCR5 gene-disrupted cells are not only resistant to R5-tropic HIV-1, including transmitted/founder (T/F) HIV-1 isolates, but also have selective advantage over CCR5 gene-undisrupted cells during R5-tropic HIV-1 infection. Importantly, using T7 endonuclease I assay we did not detect genome mutations at potential off-target sites that are highly homologous to these CCR5 sgRNAs in stably transduced cells even at 84 days post transduction. Thus we conclude that silencing of CCR5 via Cas9 and CCR5-specific sgRNAs could be a viable alternative strategy for engineering resistance against HIV-1. PMID:25541967

  6. High proportion of PD-1-expressing CD4+ T cells in adipose tissue constitutes an immunomodulatory microenvironment that may support HIV persistence.

    Science.gov (United States)

    Damouche, Abderaouf; Pourcher, Guillaume; Pourcher, Valérie; Benoist, Stéphane; Busson, Elodie; Lataillade, Jean-Jacques; Le Van, Mélanie; Lazure, Thierry; Adam, Julien; Favier, Benoit; Vaslin, Bruno; Müller-Trutwin, Michaela; Lambotte, Olivier; Bourgeois, Christine

    2017-12-01

    We and others have demonstrated that adipose tissue is a reservoir for HIV. Evaluation of the mechanisms responsible for viral persistence may lead to ways of reducing these reservoirs. Here, we evaluated the immune characteristics of adipose tissue in HIV-infected patients receiving antiretroviral therapy (ART) and in non-HIV-infected patients. We notably sought to determine whether adipose tissue's intrinsic properties and/or HIV induced alteration of the tissue environment may favour viral persistence. ART-controlled HIV infection was associated with a difference in the CD4/CD8 T-cell ratio and an elevated proportion of Treg cells in subcutaneous adipose tissue. No changes in Th1, Th2 and Th17 cell proportions or activation markers expression on T cell (Ki-67, HLA-DR) could be detected, and the percentage of CD69-expressing resident memory CD4 + T cells was not affected. Overall, our results indicate that adipose-tissue-resident CD4 + T cells are not extensively activated during HIV infection. PD-1 was expressed by a high proportion of tissue-resident memory CD4 + T cells in both HIV-infected patients and non-HIV-infected patients. Our findings suggest that adipose tissue's intrinsic immunomodulatory properties may limit immune activation and thus may strongly contribute to viral persistence. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Histone deacetylase inhibitor romidepsin induces HIV expression in CD4 T cells from patients on suppressive antiretroviral therapy at concentrations achieved by clinical dosing.

    Directory of Open Access Journals (Sweden)

    Datsen George Wei

    2014-04-01

    Full Text Available Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD, a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM compared with vorinostat (VOR; EC50 = 3,950 nM and other histone deacetylase (HDAC inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM. The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART, a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 µM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART.

  8. Class 1-Selective Histone Deacetylase (HDAC) Inhibitors Enhance HIV Latency Reversal while Preserving the Activity of HDAC Isoforms Necessary for Maximal HIV Gene Expression.

    Science.gov (United States)

    Zaikos, Thomas D; Painter, Mark M; Sebastian Kettinger, Nadia T; Terry, Valeri H; Collins, Kathleen L

    2018-03-15

    Combinations of drugs that affect distinct mechanisms of HIV latency aim to induce robust latency reversal leading to cytopathicity and elimination of the persistent HIV reservoir. Thus far, attempts have focused on combinations of protein kinase C (PKC) agonists and pan-histone deacetylase inhibitors (HDIs) despite the knowledge that HIV gene expression is regulated by class 1 histone deacetylases. We hypothesized that class 1-selective HDIs would promote more robust HIV latency reversal in combination with a PKC agonist than pan-HDIs because they preserve the activity of proviral factors regulated by non-class 1 histone deacetylases. Here, we show that class 1-selective agents used alone or with the PKC agonist bryostatin-1 induced more HIV protein expression per infected cell. In addition, the combination of entinostat and bryostatin-1 induced viral outgrowth, whereas bryostatin-1 combinations with pan-HDIs did not. When class 1-selective HDIs were used in combination with pan-HDIs, the amount of viral protein expression and virus outgrowth resembled that of pan-HDIs alone, suggesting that pan-HDIs inhibit robust gene expression induced by class 1-selective HDIs. Consistent with this, pan-HDI-containing combinations reduced the activity of NF-κB and Hsp90, two cellular factors necessary for potent HIV protein expression, but did not significantly reduce overall cell viability. An assessment of viral clearance from in vitro cultures indicated that maximal protein expression induced by class 1-selective HDI treatment was crucial for reservoir clearance. These findings elucidate the limitations of current approaches and provide a path toward more effective strategies to eliminate the HIV reservoir. IMPORTANCE Despite effective antiretroviral therapy, HIV evades eradication in a latent form that is not affected by currently available drug regimens. Pharmacologic latency reversal that leads to death of cellular reservoirs has been proposed as a strategy for

  9. Temporal expression of HIV-1 envelope proteins in baculovirus-infected insect cells: Implications for glycosylation and CD4 binding

    International Nuclear Information System (INIS)

    Murphy, C.I.; Lennick, M.; Lehar, S.M.; Beltz, G.A.; Young, E.

    1990-01-01

    Three different human immunodeficiency virus type I (HIV-1) envelope derived recombinant proteins and the full length human CD4 polypeptide were expressed in Spodoptera frugiperda (Sf9) cells. DNA constructs encoding CD4, gp120, gp160, and gp160 delta were cloned into the baculovirus expression vector pVL941 or a derivative and used to generate recombinant viruses in a cotransfection with DNA from Autographa californica nuclear polyhedrosis virus (AcMNPV). Western blotting of cell extracts of the recombinant HIV-1 proteins showed that for each construct two major bands specifically reacted with anti-HIV-1 envelope antiserum. These bands corresponded to glycosylated and nonglycosylated versions of the HIV proteins as determined by 3H-mannose labeling and tunicamycin treatment of infected cells. A time course of HIV envelope expression revealed that at early times post-infection (24 hours) the proteins were fully glycosylated and soluble in nonionic detergents. However, at later times postinfection (48 hours), expression levels of recombinant protein reached a maximum but most of the increase was due to a rise in the level of the nonglycosylated species, which was largely insoluble in nonionic detergents. Thus, it appears that Sf9 cells cannot process large amounts of glycosylated recombinant proteins efficiently. As a measure of biological activity, the CD4 binding ability of both glycosylated and nonglycosylated recombinant HIV envelope proteins was tested in a coimmunoprecipitation assay. The results showed that CD4 and the glycosylated versions of recombinant gp120 or gp160 delta specifically associated with one another in this analysis. Nonglycosylated gp120 or gp160 delta proteins from tunicamycin-treated cultures did immunoprecipitate with anti-HIV-1 antiserum but did not interact with CD4

  10. Collaborative activities and treatment outcomes in patients with HIV-associated tuberculosis in Viet Nam.

    Science.gov (United States)

    Huyen, T T T; Nhung, N V; Shewade, H D; Hoa, N B; Harries, A D

    2016-03-21

    The National Tuberculosis (TB) Programme in Viet Nam and Ho Chi Minh City (HCMC). To determine 1) at national level between 2011 and 2013, the relationship between human immunodeficiency virus (HIV) testing, uptake of TB-HIV interventions and adverse treatment outcomes among TB-HIV patients; and 2) in HCMC in 2013, patient characteristics associated with adverse outcomes. An ecological study reviewing aggregate nationwide data and a retrospective cohort review in HCMC. Nationwide, from 2011 to 2013, HIV testing increased in TB patients from 58% to 68% and antiretroviral therapy (ART) increased in TB-HIV patients from 54% to 63%. Adverse treatment outcomes in TB-HIV patients increased from 24% to 27%, largely due to transfer out (5-9% increase) and death. The Northern and Highland regions showed poor uptake of TB-HIV interventions. In HCMC, 303 (27%) of 1110 TB-HIV patients had adverse outcomes, with higher risks observed in those with previously treated TB, those diagnosed as HIV-positive before TB onset and those never placed on cotrimoxazole or ART. Despite improving HIV testing rates and TB-HIV interventions, adverse outcomes in TB-HIV patients remain at about 26%. Characteristics predicting higher risk of adverse outcomes must be addressed if Viet Nam wishes to end the TB epidemic by 2030.

  11. The effects of multiple UV exposures on HIV-LTR (long terminal repeat) expression

    International Nuclear Information System (INIS)

    Schreck, S.; Milton, J.; Panozzo, J.; Libertin, C.R.; Woloschak, G.E.; Loyola Univ., Maywood, IL

    1995-01-01

    Previous studies have shown that cellular stress agents such as UV radiation induce transcription from the long terminal repeat (LTR) of the human immunodeficiency virus (HIV). Using HeLa cells stably transfected with the HIV-LTR sequence, which transcriptionally drives the chloramphenicol acetyl transferase (CAT) reporter gene, we examined the effects of multiple exposures to UVC (254 nm) on HIV-LTR-CAT expression. Low doses (≤ 5 J m -2 ) had no effect on CAT expression, but up to 29-fold induction was observed with 10 J m -2 when cells were harvested 48 h after completion of the exposure. Little difference was noted in induction levels when cells were exposed to one 25 J m -2 dose, viable cells were harvested at 24 h, 48 h or 72 h, and cell lysates were assayed for CAT expression. Two sequential 12.5 J m -2 exposures, given 24 h apart, resulted in an additive effect on CAT expression; these two exposures produced CAT activity equivalent to that induced following a single 25 J m -2 dose. Our data suggest that HIV-LTR requires a specific threshold UV dose in order to elicit induction; a maximal induction dose is also evident; exposures higher than this maximal dose contribute no more to HIV-LTR induction in viable cells. (author)

  12. HIV-1 Reservoir Association with Immune Activation

    Directory of Open Access Journals (Sweden)

    Alejandro Vallejo

    2015-09-01

    Full Text Available In this issue of EBioMedicine, Ruggiero and colleagues describe immune activation biomarkers associated with the size of the HIV reservoir in a carefully designed cross-sectional study. The cohort consists of a homogeneous sample of HIV-1-infected patients with long-term plasma HIV-1 RNA suppression under antiretroviral treatment (ART. It is crucial to explore the potential utility of biomarkers that are easier (less labor intensive, less expensive to measure than integrated HIV DNA load, in order to quickly and accurately quantify cellular reservoirs of HIV.

  13. HIV Genome-Wide Protein Associations: a Review of 30 Years of Research

    Science.gov (United States)

    2016-01-01

    SUMMARY The HIV genome encodes a small number of viral proteins (i.e., 16), invariably establishing cooperative associations among HIV proteins and between HIV and host proteins, to invade host cells and hijack their internal machineries. As a known example, the HIV envelope glycoprotein GP120 is closely associated with GP41 for viral entry. From a genome-wide perspective, a hypothesis can be worked out to determine whether 16 HIV proteins could develop 120 possible pairwise associations either by physical interactions or by functional associations mediated via HIV or host molecules. Here, we present the first systematic review of experimental evidence on HIV genome-wide protein associations using a large body of publications accumulated over the past 3 decades. Of 120 possible pairwise associations between 16 HIV proteins, at least 34 physical interactions and 17 functional associations have been identified. To achieve efficient viral replication and infection, HIV protein associations play essential roles (e.g., cleavage, inhibition, and activation) during the HIV life cycle. In either a dispensable or an indispensable manner, each HIV protein collaborates with another viral protein to accomplish specific activities that precisely take place at the proper stages of the HIV life cycle. In addition, HIV genome-wide protein associations have an impact on anti-HIV inhibitors due to the extensive cross talk between drug-inhibited proteins and other HIV proteins. Overall, this study presents for the first time a comprehensive overview of HIV genome-wide protein associations, highlighting meticulous collaborations between all viral proteins during the HIV life cycle. PMID:27357278

  14. Construction of Nef-positive doxycycline-dependent HIV-1 variants using bicistronic expression elements

    Energy Technology Data Exchange (ETDEWEB)

    Velden, Yme U. van der; Kleibeuker, Wendy; Harwig, Alex; Klaver, Bep; Siteur-van Rijnstra, Esther; Frankin, Esmay; Berkhout, Ben; Das, Atze T., E-mail: a.t.das@amc.uva.nl

    2016-01-15

    Conditionally replicating HIV-1 variants that can be switched on and off at will are attractive tools for HIV research. We previously developed a genetically modified HIV-1 variant that replicates exclusively when doxycycline (dox) is administered. The nef gene in this HIV-rtTA variant was replaced with the gene encoding the dox-dependent rtTA transcriptional activator. Because loss of Nef expression compromises virus replication in primary cells and precludes studies on Nef function, we tested different approaches to restore Nef production in HIV-rtTA. Strategies that involved translation via an EMCV or synthetic internal ribosome entry site (IRES) failed because these elements were incompatible with efficient virus replication. Fusion protein approaches with the FMDV 2A peptide and human ubiquitin were successful and resulted in genetically-stable Nef-expressing HIV-rtTA strains that replicate more efficiently in primary T-cells and human immune system (HIS) mice than Nef-deficient variants, thus confirming the positive effect of Nef on in vivo virus replication. - Highlights: • Different approaches to encode additional proteins in the HIV-1 genome were tested. • IRES translation elements are incompatible with efficient HIV-1 replication. • Ubiquitin and 2A fusion protein approaches allow efficient HIV-1 replication. • Doxycycline-controlled HIV-1 variants that encode all viral proteins were developed. • Nef stimulates HIV-rtTA replication in primary cells and human immune system mice.

  15. Illness Representations of HIV Positive Patients Are Associated with Virologic Success.

    Science.gov (United States)

    Leone, Daniela; Borghi, Lidia; Lamiani, Giulia; Barlascini, Luca; Bini, Teresa; d'Arminio Monforte, Antonella; Vegni, Elena

    2016-01-01

    Introduction: It is important for HIV positive patients to be engaged in their care and be adherent to treatment in order to reduce disease progression and mortality. Studies found that illness representations influence adherence through the mediating role of coping behaviors. However, no study has ever tested if patient engagement to the visits mediate the relationship between illness perceptions and adherence. This study aimed to explore illness representations of HIV positive patients and test the hypothesis that illness representations predict adherence through the mediating role of a component of behavioral engagement. Methods: HIV-positive patients treated with highly active antiretroviral therapy (HAART) for at least one year and presenting to a check-up visit were eligible to participate in the study. Patients completed the Illness Perception Questionnaire-Revised. Behavioral engagement was measured based on the patients' clinical attendance to the check-up visits; adherence to HAART was measured by viral load. Undetectable viral load or HIV-RNA perception that the disease does not have serious consequences on patient's life and the prevalence of negative emotions toward HIV were associated with virologic success. On the contrary, the patient's perception that the disease has serious consequences on his/her life and the prevalence of positive emotions were associated with virologic failure. This model showed good fit indexes (CFI = 1; TLI = 1; RMSEA = 0.00; and WRMSR = 0.309). Discussion: Results do not support the mediating role of behavioral engagement in the relationship between illness representations and adherence. As perception of serious consequences coupled with positive emotions are directly associated with virologic failure, clinicians should take them into account to promote treatment adherence.

  16. Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis.

    Science.gov (United States)

    Pembroke, Thomas; Deschenes, Marc; Lebouché, Bertrand; Benmassaoud, Amine; Sewitch, Maida; Ghali, Peter; Wong, Philip; Halme, Alex; Vuille-Lessard, Elise; Pexos, Costa; Klein, Marina B; Sebastiani, Giada

    2017-10-01

    Hepatic steatosis (HS) seems common in patients infected with human immunodeficiency virus (HIV). However, the relative effect of HIV, as well as hepatitis C virus (HCV) in those co-infected, and the influence of HS on liver fibrosis progression are unclear. The LIVEr disease in HIV (LIVEHIV) is a Canadian prospective cohort study using transient elastography and associated controlled attenuation parameter (CAP) to screen for HS and liver fibrosis, in unselected HIV-infected adults. HS progression was defined as development of any grade HS (CAP ⩾248dB/m), or transition to severe HS (CAP >292dB/m), for those with any grade HS at baseline. Fibrosis progression was defined as development of significant liver fibrosis (liver stiffness measurement [LSM] >7.1kPa), or transition to cirrhosis (LSM >12.5kPa) for those with significant liver fibrosis at baseline. Cox regression analysis was used to assess predictors of HS and fibrosis progression. A prospective cohort study was conducted, which included 726 HIV-infected patients (22.7% HCV co-infected). Prevalence of any grade HS did not differ between HIV mono-infected and HIV/HCV co-infected patients (36.1% vs. 38.6%, respectively). 313 patients were followed for a median of 15.4 (interquartile range 8.5-23.0) months. The rate of HS progression was 37.8 (95% confidence interval [CI] 29.2-49.0) and 21.9 (95% CI 15.6-30.7) per 100 person-years in HIV mono-infection and HIV/HCV co-infection, respectively. HCV co-infection was an independent negative predictor of HS progression (adjusted hazard ratio [aHR] 0.50, 95% CI 0.28-0.89). HS predicted liver fibrosis progression in HIV mono-infection (aHR 4.18, 95% CI 1.21-14.5), but not in HIV/HCV co-infection. HS progresses faster and is associated with liver fibrosis progression in HIV mono-infection but not in HIV/HCV co-infection. Lay summary: Fatty liver is the most frequent liver disease in Western countries. People living with HIV seem at high risk of fatty liver due to

  17. Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells.

    Science.gov (United States)

    Arnold, Kelly B; Burgener, Adam; Birse, Kenzie; Romas, Laura; Dunphy, Laura J; Shahabi, Kamnoosh; Abou, Max; Westmacott, Garrett R; McCorrister, Stuart; Kwatampora, Jessie; Nyanga, Billy; Kimani, Joshua; Masson, Lindi; Liebenberg, Lenine J; Abdool Karim, Salim S; Passmore, Jo-Ann S; Lauffenburger, Douglas A; Kaul, Rupert; McKinnon, Lyle R

    2016-01-01

    Elevated inflammatory cytokines (EMCs) at mucosal surfaces have been associated with HIV susceptibility, but the underlying mechanisms remain unclear. We characterized the soluble mucosal proteome associated with elevated cytokine expression in the female reproductive tract. A scoring system was devised based on the elevation (upper quartile) of at least three of seven inflammatory cytokines in cervicovaginal lavage. Using this score, HIV-uninfected Kenyan women were classified as either having EMC (n=28) or not (n=68). Of 455 proteins quantified in proteomic analyses, 53 were associated with EMC (5% false discovery rate threshold). EMCs were associated with proteases, cell motility, and actin cytoskeletal pathways, whereas protease inhibitor, epidermal cell differentiation, and cornified envelope pathways were decreased. Multivariate analysis identified an optimal signature of 16 proteins that distinguished the EMC group with 88% accuracy. Three proteins in this signature were neutrophil-associated proteases that correlated with many cytokines, especially GM-CSF (granulocyte-macrophage colony-stimulating factor), IL-1β (interleukin-1β), MIP-3α (macrophage inflammatory protein-3α), IL-17, and IL-8. Gene set enrichment analyses implicated activated immune cells; we verified experimentally that EMC women had an increased frequency of endocervical CD4(+) T cells. These data reveal strong linkages between mucosal cytokines, barrier function, proteases, and immune cell movement, and propose these as potential mechanisms that increase risk of HIV acquisition.

  18. Interferon-inducible protein 10 (IP-10) is associated with viremia of early HIV-1 infection in Korean patients.

    Science.gov (United States)

    Lee, SoYong; Chung, Yoon-Seok; Yoon, Cheol-Hee; Shin, YoungHyun; Kim, SeungHyun; Choi, Byeong-Sun; Kim, Sung Soon

    2015-05-01

    Cytokines/chemokines play key roles in modulating disease progression in human immunodeficiency virus (HIV) infection. Although it is known that early HIV-1 infection is associated with increased production of proinflammatory cytokines, the relationship between cytokine levels and HIV-1 pathogenesis is not clear. The concentrations of 18 cytokines/chemokines in 30 HIV-1 negative and 208 HIV-1 positive plasma samples from Korean patients were measured by the Luminex system. Early HIV-1 infection was classified according to the Fiebig stage (FS) based on the characteristics of the patients infected with HIV-1. Concentrations of interleukin-12 (IL-12), interferon-inducible protein-10 (IP-10), macrophage inflammatory protein-1α (MIP-1α) and regulated upon activation, normal T cells expressed and secreted (RANTES) were increased significantly during the early stage of HIV-1 infection (FS II-IV) compared with the HIV-1-negative group. Of these cytokines, an elevated level of IP-10 was the only factor to be correlated positively with a higher viral load during the early stages of HIV-1 infection (FS II-IV) in Koreans (R = 0.52, P IP-10 may be an indicator for HIV-1 viremia and associated closely with viral replication in patients with early HIV-1 infection. © 2015 Wiley Periodicals, Inc.

  19. Inhibition of HIV-1 Integrase gene expression by 10-23 DNAzyme

    Indian Academy of Sciences (India)

    We have designed three novel DNAzymes, DIN54, DIN116, and DIN152, against HIV-1 Integrase gene using Mfold software and evaluated them for target site cleavage activity on the in vitro transcribed mRNA. All DNAzymes were tested for its inhibition of expression of HIV Integrase protein in the transiently transfected cell ...

  20. Non-Cationic Proteins Are Associated with HIV Neutralizing Activity in Genital Secretions of Female Sex Workers.

    Science.gov (United States)

    Birse, Kenzie D M; Cole, Amy L; Hirbod, Taha; McKinnon, Lyle; Ball, Terry B; Westmacott, Garrett R; Kimani, Joshua; Plummer, Frank; Cole, Alexander M; Burgener, Adam; Broliden, Kristina

    2015-01-01

    Cationic proteins found in cervicovaginal secretions (CVS) are known to contribute to the early antiviral immune response against HIV-infection in vitro. We here aimed to define additional antiviral factors that are over-expressed in CVS from female sex workers at high risk of infection. CVS were collected from Kenyan HIV-seronegative (n = 34) and HIV-seropositive (n = 12) female sex workers, and were compared with those from HIV-seronegative low-risk women (n = 12). The highly exposed seronegative (HESN) sex workers were further divided into those with less (n = 22) or more (n = 12) than three years of documented sex work. Cationic protein-depleted CVS were assessed for HIV-neutralizing activity by a PBMC-based HIV-neutralizing assay, and then characterized by proteomics. HIV neutralizing activity was detected in all unprocessed CVS, however only CVS from the female sex worker groups maintained its HIV neutralizing activity after cationic protein-depletion. Differentially abundant proteins were identified in the cationic protein-depleted secretions including 26, 42, and 11 in the HESN>3 yr, HESNHIV-positive groups, respectively. Gene ontology placed these proteins into functional categories including proteolysis, oxidation-reduction, and epidermal development. The proteins identified in this study include proteins previously associated with the HESN phenotype in other cohorts as well as novel proteins not yet associated with anti-HIV activities. While cationic proteins appear to contribute to the majority of the intrinsic HIV neutralizing activity in the CVS of low-risk women, a broader range of non-cationic proteins were associated with HIV neutralizing activity in HESN and HIV-positive female sex workers. These results indicate that novel protein factors found in CVS of women with high-risk sexual practices may have inherent antiviral activity, or are involved in other aspects of anti-HIV host defense, and warrant further exploration into their mode of action.

  1. Mucosal Blood Group Antigen Expression Profiles and HIV Infections: A Study among Female Sex Workers in Kenya.

    Directory of Open Access Journals (Sweden)

    Nadia Musimbi Chanzu

    Full Text Available The ABO blood group antigens are carbohydrate moieties expressed on human red blood cells however; these antigens can also be expressed on some other cells particularly the surface of epithelial cells and may be found in mucosal secretions. In many human populations 80% secrete ABO antigens (termed 'secretors' while 20% do not (termed 'non-secretors'. Furthermore, there are disease conditions that are associated with secretor status.To investigate correlations between secretor status and HIV infection among female sex workers in Nairobi, Kenya.This cross-sectional study recruited 280 female sex workers aged 18-65 years from the Pumwani Majengo cohort, Kenya. Blood typing was determined by serological techniques using monoclonal antibodies to the ABO blood group antigens. Secretor phenotyping was determined using anti-H specific lectins specific to salivary, vaginal and cervical blood group H antigen using the agglutination inhibition technique and correlated to individual HIV sero-status. Participants were additionally screened for Bacterial vaginosis, Neisseria gonorrhoea and Trichomonas vaginalis.Out of the 280 participants, 212 (75.7% were secretors and 68 (24.3% were non-secretors. The incidence of all infections: HIV, Bacterial vaginosis, Neisseria gonorrhoea and Trichomonas vaginalis was higher among secretors compared to non-secretors. However, this difference was only statistically significant for HIV infection incidence rates: HIV infected secretors (83.7% versus HIV un-infected secretors (71.8% (p = 0.029 Based on ABO phenotype stratification, the incidence of HIV infection was higher among blood group A secretors (26/52 = 50%, in comparison to B (12/39 = 33.3%: p = 0.066, AB (3/9 = 33.3%: p = 0.355, and O secretors (36/112 = 32.1%: p = 0.028.This is the first report to document the variable expression of the ABH blood group antigens profiling secretor and non-secretor phenotypes in the female genital tract among a high-risk population

  2. Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia

    Directory of Open Access Journals (Sweden)

    Hammond Robert R

    2004-05-01

    Full Text Available Abstract HIV-1-associated dementia remains a common subacute to chronic central nervous system degeneration in adult and pediatric HIV-1 infected populations. A number of viral and host factors have been implicated including the HIV-1 120 kDa envelope glycoprotein (gp120. In human post-mortem studies using confocal scanning laser microscopy for microtubule-associated protein 2 and synaptophysin, neuronal dendritic pathology correlated with dementia. In the present study, primary human CNS cultures exposed to HIV-1 gp120 at 4 weeks in vitro suffered gliosis and dendritic damage analogous to that described in association with HIV-1-associated dementia.

  3. Identification of a 251 gene expression signature that can accurately detect M. tuberculosis in patients with and without HIV co-infection.

    Directory of Open Access Journals (Sweden)

    Noor Dawany

    Full Text Available BACKGROUND: Co-infection with tuberculosis (TB is the leading cause of death in HIV-infected individuals. However, diagnosis of TB, especially in the presence of an HIV co-infection, can be limiting due to the high inaccuracy associated with the use of conventional diagnostic methods. Here we report a gene signature that can identify a tuberculosis infection in patients co-infected with HIV as well as in the absence of HIV. METHODS: We analyzed global gene expression data from peripheral blood mononuclear cell (PBMC samples of patients that were either mono-infected with HIV or co-infected with HIV/TB and used support vector machines to identify a gene signature that can distinguish between the two classes. We then validated our results using publically available gene expression data from patients mono-infected with TB. RESULTS: Our analysis successfully identified a 251-gene signature that accurately distinguishes patients co-infected with HIV/TB from those infected with HIV only, with an overall accuracy of 81.4% (sensitivity = 76.2%, specificity = 86.4%. Furthermore, we show that our 251-gene signature can also accurately distinguish patients with active TB in the absence of an HIV infection from both patients with a latent TB infection and healthy controls (88.9-94.7% accuracy; 69.2-90% sensitivity and 90.3-100% specificity. We also demonstrate that the expression levels of the 251-gene signature diminish as a correlate of the length of TB treatment. CONCLUSIONS: A 251-gene signature is described to (a detect TB in the presence or absence of an HIV co-infection, and (b assess response to treatment following anti-TB therapy.

  4. Proteomic profiling of pretreatment serum from HIV-infected patients identifies candidate markers predictive of lymphoma development

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Ludvigsen, Maja; Bendix, Knud

    2016-01-01

    . Differentially expressed proteins were identified by liquid chromatography-tandem mass spectrometry. A tissue microarray, containing diagnostic HIV-lymphoma tissue samples (N = 40), was used to investigate immunohistochemical expression of markers in tumoural lesions. RESULTS: Fourteen differentially expressed...... protein spots were detected. Using principal components analysis, spots containing immunoglobulin J chain, apolipoprotein A-I, procollagen C-endopeptidase enhancer-1 and complement C4-A were associated with lymphoma development (P ... with subsequent lymphoma compared with patients without subsequent lymphoma. In the tissue microarray, amyloid A was widely expressed, and high expression showed a tendency towards inferior outcome (log-rank 0.073). CONCLUSION: We identified several differentially expressed protein spots present already...

  5. Cloning, Expression and Purification of the Recombinant HIV-1 Tat-Nef Fusion Protein in Prokaryotic Expression System

    Directory of Open Access Journals (Sweden)

    Somayeh Kadkhodayan

    2016-07-01

    Full Text Available Abstract Background: Nef is one of the HIV-1 critical proteins, because it is essential for viral replication and AIDS disease progression and induction of immune response against it can partially inhibit viral infection. Moreover, a domain of the HIV-1 Trans-Activator of Transcription (Tat, 48-60 aa could act as a cell penetrating peptide (CPP. In current study, cloning and expression of Tat-Nef fusion protein was performed in E. coli for the first time. The protein expression was confirmed by western blot analysis and was purified using reverse staining method. Materials and Methods: In this experimental study, primarily, cloning of Tat-Nef fusion gene was done in pGEX6p2 expression vector. Then, the expression of Tat-Nef recombinat protein in E.coli BL21 (DE3 strain was performed by using IPTG inducer. The protein expression was confirmed by SDS-PAGE and western blotting using anti-Nef monoclonal antibody. Then, the recombinant fusion protein was purified from gel using reverse staining method. Results: The results of PCR analysis and enzyme digestion showed a clear band of ~ 726 bp in agarose gel indicating the correct Tat-Nef fusion cloning in pGEX6p2 prokaryotic expression vector. In addition, a 54 kDa band of Tat-Nef on SDS-PAGE revealed Tat-Nef protein expression that western blot analysis using anti-Nef monoclonal antibody confirmed it. Conclusion: The purified Tat-Nef recombinant fusion protein will be used as an antigen for protein vaccine design against HIV infection.

  6. An efficient procedure for the expression and purification of HIV-1 protease from inclusion bodies.

    Science.gov (United States)

    Nguyen, Hong-Loan Thi; Nguyen, Thuy Thi; Vu, Quy Thi; Le, Hang Thi; Pham, Yen; Trinh, Phuong Le; Bui, Thuan Phuong; Phan, Tuan-Nghia

    2015-12-01

    Several studies have focused on HIV-1 protease for developing drugs for treating AIDS. Recombinant HIV-1 protease is used to screen new drugs from synthetic compounds or natural substances. However, large-scale expression and purification of this enzyme is difficult mainly because of its low expression and solubility. In this study, we constructed 9 recombinant plasmids containing a sequence encoding HIV-1 protease along with different fusion tags and examined the expression of the enzyme from these plasmids. Of the 9 plasmids, pET32a(+) plasmid containing the HIV-1 protease-encoding sequence along with sequences encoding an autocleavage site GTVSFNF at the N-terminus and TEV plus 6× His tag at the C-terminus showed the highest expression of the enzyme and was selected for further analysis. The recombinant protein was isolated from inclusion bodies by using 2 tandem Q- and Ni-Sepharose columns. SDS-PAGE of the obtained HIV-1 protease produced a single band of approximately 13 kDa. The enzyme was recovered efficiently (4 mg protein/L of cell culture) and had high specific activity of 1190 nmol min(-1) mg(-1) at an optimal pH of 4.7 and optimal temperature of 37 °C. This procedure for expressing and purifying HIV-1 protease is now being scaled up to produce the enzyme on a large scale for its application. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Polymorphisms in DC-SIGN and L-SIGN genes are associated with HIV-1 vertical transmission in a Northeastern Brazilian population.

    Science.gov (United States)

    da Silva, Ronaldo Celerino; Segat, Ludovica; Zanin, Valentina; Arraes, Luiz Claudio; Crovella, Sergio

    2012-11-01

    DC-SIGN and L-SIGN are receptors expressed on specialized macrophages in decidua, (Hofbauer and placental capillary endothelial cells), known to interact with several pathogens, including HIV-1. To disclose the possible involvement of these molecules in the susceptibility to HIV vertical transmission, we analyzed DC-SIGN and L-SIGN gene single nucleotide polymorphisms (SNPs) in 192 HIV-1 positive children and 58 HIV-1 negative children all born to HIV-1 positive mothers, as well as 96 healthy uninfected children not exposed to HIV-1, all from Northeast Brazil. The frequency of three SNPs in the DC-SIGN promoter (-139G>A, -201G>T and -336A>G) were significantly different when comparing HIV positive children with HIV-1 exposed uninfected children, indicating an association with susceptibility to HIV-1 vertical transmission. This genetic association suggests that DC-SIGN molecule may play a role in susceptibility to HIV-1 infection through vertical transmission. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  8. Expression Profiles of Ligands for Activating Natural Killer Cell Receptors on HIV Infected and Uninfected CD4⁺ T Cells.

    Science.gov (United States)

    Tremblay-McLean, Alexandra; Bruneau, Julie; Lebouché, Bertrand; Lisovsky, Irene; Song, Rujun; Bernard, Nicole F

    2017-10-12

    Natural Killer (NK) cell responses to HIV-infected CD4 T cells (iCD4) depend on the integration of signals received through inhibitory (iNKR) and activating NK receptors (aNKR). iCD4 activate NK cells to inhibit HIV replication. HIV infection-dependent changes in the human leukocyte antigen (HLA) ligands for iNKR on iCD4 are well documented. By contrast, less is known regarding the HIV infection related changes in ligands for aNKR on iCD4. We examined the aNKR ligand profiles HIV p24⁺ HIV iCD4s that maintained cell surface CD4 (iCD4⁺), did not maintain CD4 (iCD4 - ) and uninfected CD4 (unCD4) T cells for expression of unique long (UL)-16 binding proteins-1 (ULBP-1), ULBP-2/5/6, ULBP-3, major histocompatibility complex (MHC) class 1-related (MIC)-A, MIC-B, CD48, CD80, CD86, CD112, CD155, Intercellular adhesion molecule (ICAM)-1, ICAM-2, HLA-E, HLA-F, HLA-A2, HLA-C, and the ligands to NKp30, NKp44, NKp46, and killer immunoglobulin-like receptor 3DS1 (KIR3DS1) by flow cytometry on CD4 T cells from 17 HIV-1 seronegative donors activated and infected with HIV. iCD4⁺ cells had higher expression of aNKR ligands than did unCD4. However, the expression of aNKR ligands on iCD4 where CD4 was downregulated (iCD4 - ) was similar to (ULBP-1, ULBP-2/5/6, ULBP-3, MIC-A, CD48, CD80, CD86 and CD155) or significantly lower than (MIC-B, CD112 and ICAM-2) what was observed on unCD4. Thus, HIV infection can be associated with increased expression of aNKR ligands or either baseline or lower than baseline levels of aNKR ligands, concomitantly with the HIV-mediated downregulation of cell surface CD4 on infected cells.

  9. Cardiovascular risk prediction in HIV-infected patients: comparing the Framingham, atherosclerotic cardiovascular disease risk score (ASCVD), Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) risk prediction models.

    Science.gov (United States)

    Krikke, M; Hoogeveen, R C; Hoepelman, A I M; Visseren, F L J; Arends, J E

    2016-04-01

    The aim of the study was to compare the predictions of five popular cardiovascular disease (CVD) risk prediction models, namely the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, the Framingham Heart Study (FHS) coronary heart disease (FHS-CHD) and general CVD (FHS-CVD) models, the American Heart Association (AHA) atherosclerotic cardiovascular disease risk score (ASCVD) model and the Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) model. A cross-sectional design was used to compare the cumulative CVD risk predictions of the models. Furthermore, the predictions of the general CVD models were compared with those of the HIV-specific D:A:D model using three categories ( 20%) to categorize the risk and to determine the degree to which patients were categorized similarly or in a higher/lower category. A total of 997 HIV-infected patients were included in the study: 81% were male and they had a median age of 46 [interquartile range (IQR) 40-52] years, a known duration of HIV infection of 6.8 (IQR 3.7-10.9) years, and a median time on ART of 6.4 (IQR 3.0-11.5) years. The D:A:D, ASCVD and SCORE-NL models gave a lower cumulative CVD risk, compared with that of the FHS-CVD and FHS-CHD models. Comparing the general CVD models with the D:A:D model, the FHS-CVD and FHS-CHD models only classified 65% and 79% of patients, respectively, in the same category as did the D:A:D model. However, for the ASCVD and SCORE-NL models, this percentage was 89% and 87%, respectively. Furthermore, FHS-CVD and FHS-CHD attributed a higher CVD risk to 33% and 16% of patients, respectively, while this percentage was D:A:D, ASCVD and SCORE-NL models. This could have consequences regarding overtreatment, drug-related adverse events and drug-drug interactions. © 2015 British HIV Association.

  10. Engineering and Validation of a Vector for Concomitant Expression of Rare Transfer RNA (tRNA and HIV-1 nef Genes in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Siti Aisyah Mualif

    Full Text Available Relative ease in handling and manipulation of Escherichia coli strains make them primary candidate to express proteins heterologously. Overexpression of heterologous genes that contain codons infrequently used by E. coli is related with difficulties such as mRNA instability, early termination of transcription and/or translation, deletions and/or misincorporation, and cell growth inhibition. These codon bias -associated problems are addressed by co-expressing ColE1-compatible, rare tRNA expressing helper plasmids. However, this approach has inadequacies, which we have addressed by engineering an expression vector that concomitantly expresses the heterologous protein of interest, and rare tRNA genes in E. coli. The expression vector contains three (argU, ileY, leuW rare tRNA genes and a useful multiple cloning site for easy in-frame cloning. To maintain the overall size of the parental plasmid vector, the rare tRNA genes replaced the non-essential DNA segments in the vector. The cloned gene is expressed under the control of T7 promoter and resulting recombinant protein has a C-terminal 6His tag for IMAC-mediated purification. We have evaluated the usefulness of this expression vector by expressing three HIV-1 genes namely HIV-1 p27 (nef, HIV-1 p24 (ca, and HIV-1 vif in NiCo21(DE3 E.coli and demonstrated the advantages of using expression vector that concomitantly expresses rare tRNA and heterologous genes.

  11. Factors associated with HIV testing and condom use in Mozambique: implications for programs.

    Science.gov (United States)

    Agha, Sohail

    2012-09-05

    To identify predictors of HIV testing and condom use in Mozambique. Nationally representative survey data collected in Mozambique in 2009 was analyzed. Logistic regression analysis was used for two outcomes: HIV testing and condom use. Women at a higher risk of HIV were less likely to be tested for HIV than women at a lower risk: compared to married women, HIV testing was lower among never married women (OR = 0.37, CI: 0.25-0.54); compared to women with one lifetime partner, HIV testing was lower among women with four or more lifetime partners (OR = 0.62, CI: 0.47-0.83). Large wealth differentials were observed: compared to the poorest women, HIV testing was higher among the wealthiest women (OR = 3.03, CI: 1.96-4.68). Perceived quality of health services was an important predictor of HIV testing: HIV testing was higher among women who rated health services as being of very good quality (OR = 2.12, CI: 1.49-3.00). Type of sexual partner was the strongest predictor of condom use: condom use was higher among men who reported last sex with a girlfriend (OR = 9.75, CI: 6.81-13.97) or a casual partner (OR = 11.05, CI: 7.21-16.94). Being tested for HIV during the last two years was the only programmatic variable that predicted condom use. Interestingly, being tested for HIV more than two years ago was not associated with condom use. Frequent mass media exposure was neither associated with HIV testing nor with condom use. The focus of HIV testing should shift from married women (routinely tested during antenatal care visits) to unmarried women and women with multiple sexual partners. Financial barriers to HIV testing appear to be substantial. Since HIV testing is done without a fee being charged, these barriers are presumably related to the cost of transportation to static health facilities. Mechanisms should be developed to cover the cost of transportation to health facilities. Substantially increasing community-based counseling is one way of reducing the cost of

  12. Factors associated with HIV testing and condom use in Mozambique: implications for programs

    Directory of Open Access Journals (Sweden)

    Agha Sohail

    2012-09-01

    Full Text Available Abstract Background To identify predictors of HIV testing and condom use in Mozambique. Methods Nationally representative survey data collected in Mozambique in 2009 was analyzed. Logistic regression analysis was used for two outcomes: HIV testing and condom use. Results Women at a higher risk of HIV were less likely to be tested for HIV than women at a lower risk: compared to married women, HIV testing was lower among never married women (OR = 0.37, CI: 0.25-0.54; compared to women with one lifetime partner, HIV testing was lower among women with four or more lifetime partners (OR = 0.62, CI: 0.47-0.83. Large wealth differentials were observed: compared to the poorest women, HIV testing was higher among the wealthiest women (OR = 3.03, CI: 1.96-4.68. Perceived quality of health services was an important predictor of HIV testing: HIV testing was higher among women who rated health services as being of very good quality (OR = 2.12, CI: 1.49-3.00. Type of sexual partner was the strongest predictor of condom use: condom use was higher among men who reported last sex with a girlfriend (OR = 9.75, CI: 6.81-13.97 or a casual partner (OR = 11.05, CI: 7.21-16.94. Being tested for HIV during the last two years was the only programmatic variable that predicted condom use. Interestingly, being tested for HIV more than two years ago was not associated with condom use. Frequent mass media exposure was neither associated with HIV testing nor with condom use. Conclusions The focus of HIV testing should shift from married women (routinely tested during antenatal care visits to unmarried women and women with multiple sexual partners. Financial barriers to HIV testing appear to be substantial. Since HIV testing is done without a fee being charged, these barriers are presumably related to the cost of transportation to static health facilities. Mechanisms should be developed to cover the cost of transportation to health facilities

  13. Raising awareness of HIV-related stigma and its associated ...

    African Journals Online (AJOL)

    HIV Aids will remain a problem for a long time. Many people with HIV/AIDS still live in fear of discovery because of the prevalent stigma and its associated prejudice and discrimination. This article examines how HIV-related stigma and its associated prejudice and discrimination can be addressed in a classroom ± in the field ...

  14. Variable context Markov chains for HIV protease cleavage site prediction.

    Science.gov (United States)

    Oğul, Hasan

    2009-06-01

    Deciphering the knowledge of HIV protease specificity and developing computational tools for detecting its cleavage sites in protein polypeptide chain are very desirable for designing efficient and specific chemical inhibitors to prevent acquired immunodeficiency syndrome. In this study, we developed a generative model based on a generalization of variable order Markov chains (VOMC) for peptide sequences and adapted the model for prediction of their cleavability by certain proteases. The new method, called variable context Markov chains (VCMC), attempts to identify the context equivalence based on the evolutionary similarities between individual amino acids. It was applied for HIV-1 protease cleavage site prediction problem and shown to outperform existing methods in terms of prediction accuracy on a common dataset. In general, the method is a promising tool for prediction of cleavage sites of all proteases and encouraged to be used for any kind of peptide classification problem as well.

  15. Interactive Effects of Morphine on HIV Infection: Role in HIV-Associated Neurocognitive Disorder

    Directory of Open Access Journals (Sweden)

    Pichili Vijaya Bhaskar Reddy

    2012-01-01

    Full Text Available HIV epidemic continues to be a severe public health problem and concern within USA and across the globe with about 33 million people infected with HIV. The frequency of drug abuse among HIV infected patients is rapidly increasing and is another major issue since injection drug users are at a greater risk of developing HIV associated neurocognitive dysfunctions compared to non-drug users infected with HIV. Brain is a major target for many of the recreational drugs and HIV. Evidences suggest that opiate drug abuse is a risk factor in HIV infection, neural dysfunction and progression to AIDS. The information available on the role of morphine as a cofactor in the neuropathogenesis of HIV is scanty. This review summarizes the results that help in understanding the role of morphine use in HIV infection and neural dysfunction. Studies show that morphine enhances HIV-1 infection by suppressing IL-8, downregulating chemokines with reciprocal upregulation of HIV coreceptors. Morphine also activates MAPK signaling and downregulates cAMP response element-binding protein (CREB. Better understanding on the role of morphine in HIV infection and mechanisms through which morphine mediates its effects may help in devising novel therapeutic strategies against HIV-1 infection in opiate using HIV-infected population.

  16. Social Network Characteristics Moderate the Association Between Stigmatizing Attributions About HIV and Non-adherence Among Black Americans Living with HIV: a Longitudinal Assessment.

    Science.gov (United States)

    Bogart, Laura M; Wagner, Glenn J; Green, Harold D; Mutchler, Matt G; Klein, David J; McDavitt, Bryce

    2015-12-01

    Stigma may contribute to HIV-related disparities among HIV-positive Black Americans. We examined whether social network characteristics moderate stigma's effects. At baseline and 6 months post-baseline, 147 HIV-positive Black Americans on antiretroviral treatment completed egocentric social network assessments, from which we derived a structural social support capacity measure (i.e., ability to leverage support from the network, represented by the average interaction frequency between the participant and each alter). Stigma was operationalized with an indicator of whether any social network member had expressed stigmatizing attributions of blame or responsibility about HIV. Daily medication adherence was monitored electronically. In a multivariate regression, baseline stigma was significantly related to decreased adherence over time. The association between stigma and non-adherence was attenuated among participants who increased the frequency of their interactions with alters over time. Well-connected social networks have the potential to buffer the effects of stigma.

  17. Factors related to HIV-associated neurocognitive impairment differ with age.

    Science.gov (United States)

    Fogel, Gary B; Lamers, Susanna L; Levine, Andrew J; Valdes-Sueiras, Miguel; McGrath, Michael S; Shapshak, Paul; Singer, Elyse J

    2015-02-01

    Over 50% of HIV-infected (HIV+) persons are expected to be over age 50 by 2015. The pathogenic effects of HIV, particularly in cases of long-term infection, may intersect with those of age-related illnesses and prolonged exposure to combined antiretroviral therapy (cART). One potential outcome is an increased prevalence of neurocognitive impairment in older HIV+ individuals, as well as an altered presentation of HIV-associated neurocognitive disorders (HANDs). In this study, we employed stepwise regression to examine 24 features sometimes associated with HAND in 40 older (55-73 years of age) and 30 younger (32-50 years of age) HIV+, cART-treated participants without significant central nervous system confounds. The features most effective in generating a true assessment of the likelihood of HAND diagnosis differed between older and younger cohorts, with the younger cohort containing features associated with drug abuse that were correlated to HAND and the older cohort containing features that were associated with lipid disorders mildly associated with HAND. As the HIV-infected population grows and the demographics of the epidemic change, it is increasingly important to re-evaluate features associated with neurocognitive impairment. Here, we have identified features, routinely collected in primary care settings, that provide more accurate diagnostic value than a neurocognitive screening measure among younger and older HIV individuals.

  18. Diagnosis of Oral Lesions associated with HIV/AIDS | Hamza ...

    African Journals Online (AJOL)

    HIV has a lipid envelope that has specific glycoproteins that attach to CD4 protein on cell surface. Cells which express CD4 protein are at risk of infection with HIV including CD4 lymphocytes, monocytes, macrophages, microglial cells, and langerhan's cells in skin. Disturbances in number and function of CD4 cells lead to ...

  19. Is arterial stiffness in HIV-infected individuals associated with HIV-related factors?

    International Nuclear Information System (INIS)

    Monteiro, P.; Miranda-Filho, D.B.; Bandeira, F.; Lacerda, H.R.; Chaves, H.; Albuquerque, M.F.P.M.; Montarroyos, U.R.; Ximenes, R.A.A.

    2012-01-01

    We investigated the association between pulse wave velocity (PWV) and HIV infection, antiretroviral treatment-related characteristics, viral load, immune status, and metabolic changes in a cross-sectional study nested in a cohort of HIV/AIDS patients who have been followed for metabolic and cardiovascular changes since 2007. The study included patients recruited from the cohort (N = 261) and a comparison group (N = 82) of uninfected individuals, all enrolled from April to November 2009. Aortic stiffness was estimated using the carotid-femoral PWV (Complior-Artech, Paris, France). The groups were similar with respect to age, metabolic syndrome, diabetes mellitus, Framingham score, and use of antihypertensive and hypolipidemic medications. Hypertension was more frequent among the controls. Individuals with HIV had higher triglyceride, glucose and HDL cholesterol levels. Among individuals with HIV/AIDS, those with a nadir CD4 + T-cell count <200 cells/mm 3 had a higher PWV (P = 0.01). There was no statistically significant difference when subjects were stratified by gender. Heart rate, age, male gender, and blood pressure were independently correlated with PWV. Nadir CD4 + T-cell count did not remain in the final model. There was no significance difference in PWV between HIV-infected individuals and uninfected controls. PWV was correlated with age, gender, and blood pressure across the entire population and among those infected with HIV. We recommend cohort studies to further explore the association between inflammation related to HIV infection and/or immune reconstitution and antiretroviral use and PWV

  20. HIV/AIDS and professional freedom of expression in Japan.

    Science.gov (United States)

    Matsuda, Masami

    2002-07-01

    A senior physician with a government role in Japan made a widely reported and misleading statement about Thailand's policy on HIV/AIDS patients. He claimed that in Thailand the policy is to spend public money on the prevention of HIV infection while allowing AIDS patients to die untreated. The author, a community nursing specialist in Japan with first-hand knowledge of HIV/AIDS policy in Thailand, thought that this statement would influence attitudes negatively in Japan. However, speaking out about this misrepresentation of the facts carried certain risks. Although freedom of expression is valued in Japan, in practice it is not easy to contradict senior medical professionals. The author uses his experience of this difficult professional situation to teach nurses how to approach speaking out in the public interest.

  1. Unpolarized release of vaccinia virus and HIV antigen by colchicine treatment enhances intranasal HIV antigen expression and mucosal humoral responses.

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    Yan Zhang

    Full Text Available The induction of a strong mucosal immune response is essential to building successful HIV vaccines. Highly attenuated recombinant HIV vaccinia virus can be administered mucosally, but even high doses of immunization have been found unable to induce strong mucosal antibody responses. In order to solve this problem, we studied the interactions of recombinant HIV vaccinia virus Tiantan strain (rVTT-gagpol in mucosal epithelial cells (specifically Caco-2 cell layers and in BALB/c mice. We evaluated the impact of this virus on HIV antigen delivery and specific immune responses. The results demonstrated that rVTT-gagpol was able to infect Caco-2 cell layers and both the nasal and lung epithelia in BALB/c mice. The progeny viruses and expressed p24 were released mainly from apical surfaces. In BALB/c mice, the infection was limited to the respiratory system and was not observed in the blood. This showed that polarized distribution limited antigen delivery into the whole body and thus limited immune response. To see if this could be improved upon, we stimulated unpolarized budding of the virus and HIV antigens by treating both Caco-2 cells and BALB/c mice with colchicine. We found that, in BALB/c mice, the degree of infection and antigen expression in the epithelia went up. As a result, specific immune responses increased correspondingly. Together, these data suggest that polarized budding limits antigen delivery and immune responses, but unpolarized distribution can increase antigen expression and delivery and thus enhance specific immune responses. This conclusion can be used to optimize mucosal HIV vaccine strategies.

  2. National Institute on Drug Abuse symposium report: drugs of abuse, dopamine, and HIV-associated neurocognitive disorders/HIV-associated dementia.

    Science.gov (United States)

    Purohit, Vishnudutt; Rapaka, Rao; Frankenheim, Jerry; Avila, Albert; Sorensen, Roger; Rutter, Joni

    2013-04-01

    The National Institute on Drug Abuse organized a symposium on drugs of abuse, dopamine, and HIV-associated neurocognitive disorders (HAND)/HIV-associated dementia (HAD) in Rockville, Maryland, October 4, 2011. The purpose of this symposium was to evaluate the potential role of dopamine in the potentiation of HAND/HAD by drugs of abuse. A summary of the symposium has been presented in this report.

  3. Post-traumatic stress is associated with verbal learning, memory, and psychomotor speed in HIV-infected and HIV-uninfected women.

    Science.gov (United States)

    Rubin, Leah H; Pyra, Maria; Cook, Judith A; Weber, Kathleen M; Cohen, Mardge H; Martin, Eileen; Valcour, Victor; Milam, Joel; Anastos, Kathryn; Young, Mary A; Alden, Christine; Gustafson, Deborah R; Maki, Pauline M

    2016-04-01

    The prevalence of post-traumatic stress disorder (PTSD) is higher among HIV-infected (HIV+) women compared with HIV-uninfected (HIV-) women, and deficits in episodic memory are a common feature of both PTSD and HIV infection. We investigated the association between a probable PTSD diagnosis using the PTSD Checklist-Civilian (PCL-C) version and verbal learning and memory using the Hopkins Verbal Learning Test in 1004 HIV+ and 496 at-risk HIV- women. HIV infection was not associated with a probable PTSD diagnosis (17% HIV+, 16% HIV-; p = 0.49) but was associated with lower verbal learning (p memory scores (p memory (p < 0.01) and psychomotor speed (p < 0.001). The particular pattern of cognitive correlates of probable PTSD varied depending on exposure to sexual abuse and/or violence, with exposure to either being associated with a greater number of cognitive domains and a worse cognitive profile. A statistical interaction between HIV serostatus and PTSD was observed on the fine motor skills domain (p = 0.03). Among women with probable PTSD, HIV- women performed worse than HIV+ women on fine motor skills (p = 0.01), but among women without probable PTSD, there was no significant difference in performance between the groups (p = 0.59). These findings underscore the importance of considering mental health factors as correlates to cognitive deficits in women with HIV.

  4. The association of perceived stress and verbal memory is greater in HIV-infected versus HIV-uninfected women.

    Science.gov (United States)

    Rubin, Leah H; Cook, Judith A; Weber, Kathleen M; Cohen, Mardge H; Martin, Eileen; Valcour, Victor; Milam, Joel; Anastos, Kathryn; Young, Mary A; Alden, Christine; Gustafson, Deborah R; Maki, Pauline M

    2015-08-01

    In contrast to findings from cohorts comprised primarily of HIV-infected men, verbal memory deficits are the largest cognitive deficit found in HIV-infected women from the Women's Interagency HIV Study (WIHS), and this deficit is not explained by depressive symptoms or substance abuse. HIV-infected women may be at greater risk for verbal memory deficits due to a higher prevalence of cognitive risk factors such as high psychosocial stress and lower socioeconomic status. Here, we investigate the association between perceived stress using the Perceived Stress Scale (PSS-10) and verbal memory performance using the Hopkins Verbal Learning Test (HVLT) in 1009 HIV-infected and 496 at-risk HIV-uninfected WIHS participants. Participants completed a comprehensive neuropsychological test battery which yielded seven cognitive domain scores, including a primary outcome of verbal memory. HIV infection was not associated with a higher prevalence of high perceived stress (i.e., PSS-10 score in the top tertile) but was associated with worse performance on verbal learning (p memory (p stress was associated with poorer performance in those cognitive domains (p's stress interaction was found only for the verbal memory domain (p = 0.02); among HIV-infected women only, high stress was associated with lower performance (p's memory measure in particular. These findings suggest that high levels of perceived stress contribute to the deficits in verbal memory observed in WIHS women.

  5. Association of Internalized and Social Network Level HIV Stigma With High-Risk Condomless Sex Among HIV-Positive African American Men

    OpenAIRE

    Wagner, Glenn J.; Bogart, Laura M.; Klein, David J.; Green, Harold D.; Mutchler, Matt G.; McDavitt, Bryce; Hilliard, Charles

    2015-01-01

    We examined whether internalized HIV stigma and perceived HIV stigma from social network members (alters), including the most popular and most similar alter, predicted condomless intercourse with negative or unknown HIV status partners among 125 African American HIV-positive men. In a prospective, observational study, participants were administered surveys at baseline and months 6 and 12, with measures including sexual behavior, internalized HIV stigma, and an egocentric social network assess...

  6. Association between depressive symptoms, CD4 count and HIV viral suppression among HIV-HCV co-infected people.

    Science.gov (United States)

    Aibibula, Wusiman; Cox, Joseph; Hamelin, Anne-Marie; Moodie, Erica E M; Anema, Aranka; Klein, Marina B; Brassard, Paul

    2018-05-01

    Depressive symptoms are associated with poor HIV viral control and immune recovery among people living with HIV. However, no prior studies assessed this association exclusively among people co-infected with HIV-hepatitis C virus (HCV). While people with HIV only and those with HIV-HCV co-infection share many characteristics, co-infected people may become more susceptible to the effects of depressive symptoms on health outcomes. We assessed this association exclusively among people co-infected with HIV-HCV in Canada using data from the Food Security & HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC). Stabilized inverse probability weighted marginal structural model was used to account for potential time-varying confounders. A total of 725 participants were enrolled between 2012 and 2015. At baseline, 52% of participants reported depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count was 466 (IQR 300-665). People experiencing depressive symptoms had 1.32 times (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had comparable CD4 count to people who did not experience depressive symptoms (fold change of CD4 = 0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a risk factor for incomplete short-term HIV viral suppression among people co-infected with HIV-HCV. Therefore, depressive symptoms screening and related counseling may improve HIV related health outcomes and reduce HIV transmission.

  7. Predicting Bevirimat resistance of HIV-1 from genotype

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    Hoffmann Daniel

    2010-01-01

    Full Text Available Abstract Background Maturation inhibitors are a new class of antiretroviral drugs. Bevirimat (BVM was the first substance in this class of inhibitors entering clinical trials. While the inhibitory function of BVM is well established, the molecular mechanisms of action and resistance are not well understood. It is known that mutations in the regions CS p24/p2 and p2 can cause phenotypic resistance to BVM. We have investigated a set of p24/p2 sequences of HIV-1 of known phenotypic resistance to BVM to test whether BVM resistance can be predicted from sequence, and to identify possible molecular mechanisms of BVM resistance in HIV-1. Results We used artificial neural networks and random forests with different descriptors for the prediction of BVM resistance. Random forests with hydrophobicity as descriptor performed best and classified the sequences with an area under the Receiver Operating Characteristics (ROC curve of 0.93 ± 0.001. For the collected data we find that p2 sequence positions 369 to 376 have the highest impact on resistance, with positions 370 and 372 being particularly important. These findings are in partial agreement with other recent studies. Apart from the complex machine learning models we derived a number of simple rules that predict BVM resistance from sequence with surprising accuracy. According to computational predictions based on the data set used, cleavage sites are usually not shifted by resistance mutations. However, we found that resistance mutations could shorten and weaken the α-helix in p2, which hints at a possible resistance mechanism. Conclusions We found that BVM resistance of HIV-1 can be predicted well from the sequence of the p2 peptide, which may prove useful for personalized therapy if maturation inhibitors reach clinical practice. Results of secondary structure analysis are compatible with a possible route to BVM resistance in which mutations weaken a six-helix bundle discovered in recent experiments

  8. Associations of hormonal contraceptive use with measures of HIV disease progression and antiretroviral therapy effectiveness.

    Science.gov (United States)

    Whiteman, Maura K; Jeng, Gary; Samarina, Anna; Akatova, Natalia; Martirosyan, Margarita; Kissin, Dmitry M; Curtis, Kathryn M; Marchbanks, Polly A; Hillis, Susan D; Mandel, Michele G; Jamieson, Denise J

    2016-01-01

    To examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness. A prospective cohort study of women with prevalent HIV infection in St. Petersburg, Russia, was conducted. After contraceptive counseling, participants chose to use combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male condoms for pregnancy prevention. Among participants not using ART at enrollment, we used multivariate Cox regression to assess the association between current (time-varying) contraceptive use and disease progression, measured by the primary composite outcome of CD4 decline to contraceptive method. During a total of 5233 months follow-up among participants not using ART with enrollment CD4 ≥350 cells/mm(3) (n=315), 97 experienced disease progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) 0.56-1.48] nor DMPA (aHR 1.28, 95% CI 0.71-2.31) was associated with a statistically significant increased risk for disease progression compared with use of nonhormonal methods (IUD or condoms). Among participants using ART at enrollment (n=77), we found no statistically significant differences in the predicted mean changes in CD4 cell count comparing current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods. Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Published by Elsevier Inc.

  9. Expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.

    Directory of Open Access Journals (Sweden)

    Birgitte Lindegaard

    Full Text Available BACKGROUND: Fibroblast growth factor (FGF-21 is a novel regulator of glucose and lipid metabolism. Recently, increased FGF-21 mRNA expression in muscle was found in patients with type 2 diabetes, but the role for FGF-21 in muscle is not well understood. Patients with HIV-infection and lipodystrophy are characterised by various degree of lipid-driven insulin resistance. We hypothesized that muscle FGF-21 mRNA would be altered in HIV patients with lipodystrophy. DESIGN: Twenty-five HIV-infected men with lipodystrophy (LD and 15 age-matched healthy controls, received an oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp (50 mU/m2/min combined with 6,6-H2 glucose infusion. Muscle biopsies were obtained and FGF-21 mRNA and glycogen synthase (GS activity were measured. RESULTS: Subjects with HIV were insulin resistant compared with non-HIV subjects. Compared to controls, HIV subjects demonstrated a twofold increase of plasma FGF-21 from 70.4±56.8 pg/ml vs 109.1±71.8 pg/ml, respectively (p = 0.04 and an eight-fold increase in muscular FGF-21 mRNA expression (p = 0.001. Muscle FGF-21 mRNA correlated inversely with the rate of disappearance of glucose during insulin clamp (r = -0.54, p = 0.0009, and the GS fractional velocity in muscle (r = -0.39, p = 0.03, and directly with fasting insulin (r = 0.50, p = 0.0022, HOMA-IR (r = 0.47, p = 0.004, triglycerides (r = 0.60. P = 0.0001, waist-to-hip ratio (r = 0.51, p = 0.0001 and limb fat mass (-0.46, p = 0.004, but not to plasma FGF-21. CONCLUSION: FGF-21 mRNA is increased in skeletal muscle in HIV patients and correlates to whole-body (primarily reflecting muscle insulin resistance, but not to plasma FGF-21. Those findings add to the evidence that FGF-21 is a myokine and may suggest that muscle FGF-21 is working in a local manner.

  10. Ecological association between HIV and concurrency point ...

    African Journals Online (AJOL)

    Ecological association between HIV and concurrency point-prevalence in South Africa's ethnic groups. Chris Kenyon. Abstract. HIV prevalence between different ethnic groups within South Africa exhibits considerable variation. Numerous authors believe that elevated sexual partner concurrency rates are important in the ...

  11. Association of Internalized and Social Network Level HIV Stigma With High-Risk Condomless Sex Among HIV-Positive African American Men.

    Science.gov (United States)

    Wagner, Glenn J; Bogart, Laura M; Klein, David J; Green, Harold D; Mutchler, Matt G; McDavitt, Bryce; Hilliard, Charles

    2016-08-01

    We examined whether internalized HIV stigma and perceived HIV stigma from social network members (alters), including the most popular and most similar alter, predicted condomless intercourse with negative or unknown HIV status partners among 125 African American HIV-positive men. In a prospective, observational study, participants were administered surveys at baseline and months 6 and 12, with measures including sexual behavior, internalized HIV stigma, and an egocentric social network assessment that included several measures of perceived HIV stigma among alters. In longitudinal multivariable models comparing the relative predictive value of internalized stigma versus various measures of alter stigma, significant predictors of having had condomless intercourse included greater internalized HIV stigma (in all models), the perception that a popular (well-connected) alter or alter most like the participant agrees with an HIV stigma belief, and the interaction of network density with having any alter that agrees with a stigma belief. The interaction indicated that the protective effect of greater density (connectedness between alters) in terms of reduced risk behavior dissipated in the presence of perceived alter stigma. These findings call for interventions that help people living with HIV to cope with their diagnosis and reduce stigma, and inform the targets of social network-based and peer-driven HIV prevention interventions.

  12. Liver stiffness is not associated with short- and long-term plasma HIV RNA replication in immunocompetent patients with HIV infection and with HIV/HCV coinfection

    Science.gov (United States)

    Parisi, Saverio Giuseppe; Basso, Monica; Mengoli, Carlo; Scaggiante, Renzo; Andreis, Samantha; Franzetti, Marzia Maria; Cattelan, Anna Maria; Zago, Daniela; Cruciani, Mario; Andreoni, Massimo; Piovesan, Sara; Palù, Giorgio; Alberti, Alfredo

    2017-01-01

    Background Human immunodeficiency virus (HIV) may be directly responsible for liver damage but there are contrasting data regarding the influence of detectable plasma viremia. We analyzed the influence of plasma HIV RNA (pHIV) detectability and of other clinical and viro-immunological variables on liver stiffness (LS) measurement in adult immunocompetent HIV-monoinfected patients and in patients coinfected with hepatitis C virus (HCV). Methods Logistic regression analysis was performed using the value of LS>7.1 kPa as the dependent variable. A linear regression model was applied using LS measurement after log10 transformation (lkpa) as the dependent variable and we analyzed the predicted values versus the observed lkpa values; pHIV was classified as detectable or undetectable in the 12- and 36-month study periods before LS measurement. Results We studied 251 patients (178 with HIV monoinfection), most of whom were on antiviral treatment; 36-month study time was available for 154 subjects. The mean CD4+ cell count was 634 cells/mm3 in HIV-monoinfected patients and 606 cells/mm3 in coinfected patients. No difference in LS was found between patients with detectable or undetectable pHIV in either the 12- or the 36-month study period before transient elastography. The mean LS was higher in HIV/HCV coinfected patients (P<0.0001) than in the HIV-monoinfected subjects; lkpa was positively correlated with HCV coinfection (P<0.0001) and aspartate aminotransferase levels (P<0.0001). Detectable pHIV failed to reach significance. Eight HIV-monoinfected patients had a predicted LS measurement lower than the observed one, while eight patients had the opposite result. Conclusion LS was not correlated with ongoing HIV replication during the 12- and 36-month study periods in immunocompetent HIV-monoinfected and HIV/HCV-coinfected patients. PMID:28845109

  13. Is arterial stiffness in HIV-infected individuals associated with HIV-related factors?

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    Monteiro, P. [Serviço de Doenças Infecciosas, Faculdade de Medicina, Universidade de Pernambuco, Recife, PE (Brazil); Miranda-Filho, D.B. [Departamento de Medicina Clínica, Faculdade de Medicina, Universidade de Pernambuco, Recife, PE (Brazil); Bandeira, F. [Serviço de Endocrinologia, Faculdade de Medicina, Universidade de Pernambuco, Recife, PE (Brazil); Lacerda, H.R. [Departamento de Medicina Clínica, Faculdade de Medicina, Universidade de Pernambuco, Recife, PE (Brazil); Departamento de Medicina Tropical, Faculdade de Medicina, Universidade Federal de Pernambuco, Recife, PE (Brazil); Chaves, H. [Departamento de Cardiologia, Faculdade de Medicina, Universidade Federal de Pernambuco, Recife, PE (Brazil); Albuquerque, M.F.P.M. [Centro de Pesquisa Aggeu Magalhães,FIOCRUZ, Recife, PE (Brazil); Montarroyos, U.R. [Departamento de Medicina Tropical, Faculdade de Medicina, Universidade Federal de Pernambuco, Recife, PE (Brazil); Ximenes, R.A.A. [Departamento de Medicina Clínica, Faculdade de Medicina, Universidade de Pernambuco, Recife, PE (Brazil); Departamento de Medicina Tropical, Faculdade de Medicina, Universidade Federal de Pernambuco, Recife, PE (Brazil)

    2012-07-13

    We investigated the association between pulse wave velocity (PWV) and HIV infection, antiretroviral treatment-related characteristics, viral load, immune status, and metabolic changes in a cross-sectional study nested in a cohort of HIV/AIDS patients who have been followed for metabolic and cardiovascular changes since 2007. The study included patients recruited from the cohort (N = 261) and a comparison group (N = 82) of uninfected individuals, all enrolled from April to November 2009. Aortic stiffness was estimated using the carotid-femoral PWV (Complior-Artech, Paris, France). The groups were similar with respect to age, metabolic syndrome, diabetes mellitus, Framingham score, and use of antihypertensive and hypolipidemic medications. Hypertension was more frequent among the controls. Individuals with HIV had higher triglyceride, glucose and HDL cholesterol levels. Among individuals with HIV/AIDS, those with a nadir CD4{sup +} T-cell count <200 cells/mm{sup 3} had a higher PWV (P = 0.01). There was no statistically significant difference when subjects were stratified by gender. Heart rate, age, male gender, and blood pressure were independently correlated with PWV. Nadir CD4{sup +} T-cell count did not remain in the final model. There was no significance difference in PWV between HIV-infected individuals and uninfected controls. PWV was correlated with age, gender, and blood pressure across the entire population and among those infected with HIV. We recommend cohort studies to further explore the association between inflammation related to HIV infection and/or immune reconstitution and antiretroviral use and PWV.

  14. Is arterial stiffness in HIV-infected individuals associated with HIV-related factors?

    Directory of Open Access Journals (Sweden)

    P. Monteiro

    Full Text Available We investigated the association between pulse wave velocity (PWV and HIV infection, antiretroviral treatment-related characteristics, viral load, immune status, and metabolic changes in a cross-sectional study nested in a cohort of HIV/AIDS patients who have been followed for metabolic and cardiovascular changes since 2007. The study included patients recruited from the cohort (N = 261 and a comparison group (N = 82 of uninfected individuals, all enrolled from April to November 2009. Aortic stiffness was estimated using the carotid-femoral PWV (Complior-Artech, Paris, France. The groups were similar with respect to age, metabolic syndrome, diabetes mellitus, Framingham score, and use of antihypertensive and hypolipidemic medications. Hypertension was more frequent among the controls. Individuals with HIV had higher triglyceride, glucose and HDL cholesterol levels. Among individuals with HIV/AIDS, those with a nadir CD4+ T-cell count <200 cells/mm³ had a higher PWV (P = 0.01. There was no statistically significant difference when subjects were stratified by gender. Heart rate, age, male gender, and blood pressure were independently correlated with PWV. Nadir CD4+ T-cell count did not remain in the final model. There was no significance difference in PWV between HIV-infected individuals and uninfected controls. PWV was correlated with age, gender, and blood pressure across the entire population and among those infected with HIV. We recommend cohort studies to further explore the association between inflammation related to HIV infection and/or immune reconstitution and antiretroviral use and PWV.

  15. Regulation of HIV-Gag Expression and Targeting to the Endolysosomal/Secretory Pathway by the Luminal Domain of Lysosomal-Associated Membrane Protein (LAMP-1) Enhance Gag-Specific Immune Response

    Science.gov (United States)

    Lucas, Carolina Gonçalves de Oliveira; Rigato, Paula Ordonhez; Gonçalves, Jorge Luiz Santos; Sato, Maria Notomi; Maciel, Milton; Peçanha, Ligia Maria Torres; August, J. Thomas; de Azevedo Marques, Ernesto Torres; de Arruda, Luciana Barros

    2014-01-01

    We have previously demonstrated that a DNA vaccine encoding HIV-p55gag in association with the lysosomal associated membrane protein-1 (LAMP-1) elicited a greater Gag-specific immune response, in comparison to a DNA encoding the native gag. In vitro studies have also demonstrated that LAMP/Gag was highly expressed and was present in MHCII containing compartments in transfected cells. In this study, the mechanisms involved in these processes and the relative contributions of the increased expression and altered traffic for the enhanced immune response were addressed. Cells transfected with plasmid DNA constructs containing p55gag attached to truncated sequences of LAMP-1 showed that the increased expression of gag mRNA required p55gag in frame with at least 741 bp of the LAMP-1 luminal domain. LAMP luminal domain also showed to be essential for Gag traffic through lysosomes and, in this case, the whole sequence was required. Further analysis of the trafficking pathway of the intact LAMP/Gag chimera demonstrated that it was secreted, at least in part, associated with exosome-like vesicles. Immunization of mice with LAMP/gag chimeric plasmids demonstrated that high expression level alone can induce a substantial transient antibody response, but targeting of the antigen to the endolysosomal/secretory pathways was required for establishment of cellular and memory response. The intact LAMP/gag construct induced polyfunctional CD4+ T cell response, which presence at the time of immunization was required for CD8+ T cell priming. LAMP-mediated targeting to endolysosomal/secretory pathway is an important new mechanistic element in LAMP-mediated enhanced immunity with applications to the development of novel anti-HIV vaccines and to general vaccinology field. PMID:24932692

  16. Neoplasms-associated deaths in HIV-1 infected and non-infected patients in Bahia, Brazil.

    Science.gov (United States)

    Marques, Marinho; Luz, Estela; Leal, Mateus; Oliveira, João Vitor; Patrício, Rejane; Netto, Eduardo Martins; Brites, Carlos

    2018-05-01

    HIV-infected patients are at a higher risk to develop malignancies than general population. Although AIDS-related malignancies are a common feature of late-stage disease, patients under successful antiretroviral therapy also have an increased risk for development of non-AIDS malignancies. To compare the frequency and characteristics of adults HIV-infected patients and general population who died of malignancies in Bahia, Brazil from January 2000 to December 2010. National Information System on Mortality (SIM) was searched to identify all deaths in the study period caused by malignancies in general population and in HIV patients. The frequency of malignancies in these two groups was compared. For HIV patients we also recorded the last HIV-1 RNA plasma viral load and CD4+ cells count, retrieved from oficial databases on laboratory monitoring for HIV patients. In the study period 733,645 deaths were reported, 677,427 (92.3%) of them in individual older than 13 years. Malignancies were the cause of death in 77,174 (11.4%) of them, and 5156 (0.8%) were associated to HIV/Aids. Among deaths of HIV/Aids patients, Kaposi´s sarcoma was the most prevalent malignancy (OR: 309.7; 95% CI: 177-544), followed by non-Hodgkin lymphoma (OR: 10.1; 95% CI: 5.3-19.3), Hodgkin´s lymphoma (OR: 4.3; 95% CI: 2.2-8.4), and cranial nervous malignancies (OR: 3.3; 95% CI:1.6-7.0). HIV patients died at a significantly lower age (43.7 years), than general population (64.5 years, p HIV infection is a clear risk fator for development of some malignancies, and is associated with early mortality, compared to general population. The level of CD4+ cells count predicts the type of malignancies causing death in this population. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Structural similarity-based predictions of protein interactions between HIV-1 and Homo sapiens

    Directory of Open Access Journals (Sweden)

    Gomez Shawn M

    2010-04-01

    Full Text Available Abstract Background In the course of infection, viruses such as HIV-1 must enter a cell, travel to sites where they can hijack host machinery to transcribe their genes and translate their proteins, assemble, and then leave the cell again, all while evading the host immune system. Thus, successful infection depends on the pathogen's ability to manipulate the biological pathways and processes of the organism it infects. Interactions between HIV-encoded and human proteins provide one means by which HIV-1 can connect into cellular pathways to carry out these survival processes. Results We developed and applied a computational approach to predict interactions between HIV and human proteins based on structural similarity of 9 HIV-1 proteins to human proteins having known interactions. Using functional data from RNAi studies as a filter, we generated over 2000 interaction predictions between HIV proteins and 406 unique human proteins. Additional filtering based on Gene Ontology cellular component annotation reduced the number of predictions to 502 interactions involving 137 human proteins. We find numerous known interactions as well as novel interactions showing significant functional relevance based on supporting Gene Ontology and literature evidence. Conclusions Understanding the interplay between HIV-1 and its human host will help in understanding the viral lifecycle and the ways in which this virus is able to manipulate its host. The results shown here provide a potential set of interactions that are amenable to further experimental manipulation as well as potential targets for therapeutic intervention.

  18. Ectopic expression of anti-HIV-1 shRNAs protects CD8+ T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation

    International Nuclear Information System (INIS)

    Kamata, Masakazu; Kim, Patrick Y.; Ng, Hwee L.; Ringpis, Gene-Errol E.; Kranz, Emiko; Chan, Joshua; O'Connor, Sean; Yang, Otto O.; Chen, Irvin S.Y.

    2015-01-01

    Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients. We hypothesize that ectopic expression of CD4ζ on CD8 + T cells renders them susceptible to HIV-1 infection, resulting in poor survival of those cells. To test this possibility, highly purified CD8 + T cells were genetically modified with a CD4ζ-encoding lentiviral vector and infected with HIV-1. CD8 + T cells were vulnerable to HIV-1 infection upon expression of CD4ζ as evidenced by elevated levels of p24 Gag in cells and culture supernatants. Concurrently, the number of CD4ζ-modified CD8 + T cells was reduced relative to control cells upon HIV-1 infection. To protect these cells from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed by our group together with CD4ζ. This combination vector was able to suppress HIV-1 infection without impairing HIV-1-dependent effector activities of CD4ζ. In addition, the number of CD4ζ-modified CD8 + T cells maintained similar levels to that of the control even under HIV-1 infection. These results suggest that protecting CD4ζ-modified CD8 + T cells from HIV-1 infection is required for prolonged HIV-1-specific immune surveillance. - Highlights: • Ectopic expression of CD4ζ CAR in CD8 + T cells renders them susceptible to HIV-1 infection. • Co-expression of two anti-HIV-1 shRNAs protects CD4ζ CAR-modified CD8 + T cells from HIV-1 infection. • Protecting CD4ζ CAR-modified CD8 + T cells from HIV-1 infection suppresses its cytopathic effect

  19. Factors associated with HIV among female sex workers in a high HIV prevalent state of India.

    Science.gov (United States)

    Medhi, Gajendra Kumar; Mahanta, Jagadish; Paranjape, Ramesh S; Adhikary, Rajatashuvra; Laskar, Nabjyoti; Ngully, P

    2012-01-01

    The study was carried out to assess the factors associated with HIV seropositivity among female sex workers (FSWs) in Dimapur, Nagaland, a high HIV prevalence state of India. A total of 426 FSWs were recruited into the study using respondent driven sampling (RDS). Data on demographic characteristics, sexual and injecting risk behaviours were collected from them and were tested for HIV, Syphilis, Neisseria gonorrhoeae and Chlamydia trachomatis. RDS-weighted univariate and multivariate logistic regression analysis was performed to assess the factors associated with HIV seropositivity. Consistent condom use with regular and occasional sexual clients was 9% and 16.4%, respectively. About 25% of the participants ever used and 5.7% ever injected illicit drugs. RDS adjusted HIV prevalence was 11.6%. In the univariate analysis, factors associated with HIV were initiating sexual intercourse before the age of 15 years, ≥2 years duration of sex work, serving clients at lodge/hotel, positive test result for one or more sexually transmitted infections (STIs), lifetime history of injecting drug use, lifetime history of consuming illicit drugs, ever having exchanged sex for drugs, having sexual partners who engaged in risky injecting practices and having been widowed or divorced. In multivariate analysis, factors found to be independently associated with HIV included lifetime injecting drug use, initiating sexual intercourse before the age of 15 years, positive test result for one or more STIs and having been widowed. Injecting drug use was found to be most potent independent risk factor for HIV (OR: 3.17, CI: 1.02-9.89). Because of lower consistent condom use among them, FSWs may act as bridge for HIV transmission to general population from injecting drug users (IDU) through their sexual clients. The informations from this study may be useful for enriching the HIV preventions effort for FSWs in this region.

  20. The association between HIV/AIDS-related knowledge and perception of risk for infection: a systematic review.

    Science.gov (United States)

    Ndugwa Kabwama, Steven; Berg-Beckhoff, Gabriele

    2015-11-01

    This systematic review tries to elucidate the association between what people know about HIV/AIDS and how they perceive their risk of infection. The initial search for articles yielded 1,595 abstracts, 16 of which met the inclusion criteria. Five studies found a positive correlation, four reported a negative correlation and seven found no association between knowledge and risk perception. It was found that the existing psychometrically sound measure of HIV/AIDS risk perception had not been used in any of the studies. The context in which the risk is assessed is pivotal to whether an association between knowledge and the perceived risk is found. Biases in judgement such as optimistic bias, psychological distancing, anchoring bias and overconfidence also explain how knowledge may fail to predict risk perception. It was concluded that the association between HIV/AIDS knowledge and risk perception might follow a continuum from positive to no association and finally to negative. The hypothesis, however, still needs to be studied further. © Royal Society for Public Health 2015.

  1. Affective differences in Iowa Gambling Task performance associated with sexual risk taking and substance use among HIV-positive and HIV-negative men who have sex with men

    Science.gov (United States)

    Golub, Sarit A.; Thompson, Louisa I.; Kowalczyk, William J.

    2016-01-01

    We investigated the relationship between emotional distress and decision-making in sexual risk and substance use behavior among 174 (ages 25 to 50, 53% black) men who have sex with men (MSM), a population at increased risk for HIV. The sample was stratified by HIV status. Measures of affective decision-making (Iowa Gambling Task, IGT, Bechara et al., 1994), depression, anxiety, sex acts, and substance use during the past 60 days were collected at our research center. Negative binomial regression models were used to examine the relationship between age, HIV status, anxiety, depression, and IGT performance in the prediction of number of risky sex acts and substance use days. Among those without anxiety or depression, both number of risky sex acts and drug use days decreased with better performance during risky trials (i.e., last two blocks) of the IGT. For those with higher rates of anxiety, but not depression, IGT risk trial performance and risky sex acts increased concomitantly. Anxiety also interacted with IGT performance across all trials to predict substance use, such that anxiety was associated with greater substance use among those with better IGT performance. The opposite was true for those with depression, but only during risk trials. HIV-positive participants reported fewer substance use days than HIV-negative participants, but there was no difference in association between behavior and IGT performance by HIV status. Our findings suggest that anxiety may exacerbate risk-taking behavior when affective decision-making ability is intact. The relationship between affective decision-making and risk taking may be sensitive to different profiles of emotional distress, as well as behavioral context. Investigations of affective decision-making in sexual risk taking and substance use should examine different distress profiles separately, with implications for HIV prevention efforts. PMID:26745769

  2. Disturbed amino acid metabolism in HIV: association with neuropsychiatric symptoms

    Directory of Open Access Journals (Sweden)

    Johanna M Gostner

    2015-07-01

    Full Text Available Blood levels of the amino acid phenylalanine, as well as of the tryptophan breakdown product kynurenine, are found to be elevated in human immunodeficiency virus type 1 (HIV-1-infected patients. Both essential amino acids, tryptophan and phenylalanine are important precursor molecules for neurotransmitter biosynthesis. Thus, dysregulated amino acid metabolism may be related to disease-associated neuropsychiatric symptoms such as development of depression, fatigue, and cognitive impairment.Increased phenylalanine/tyrosine and kynurenine/tryptophan ratios are associated with immune activation in patients with HIV-1 infection and decrease upon effective antiretroviral therapy. Recent large-scale metabolic studies have confirmed the crucial involvement of tryptophan and phenylalanine metabolism in HIV-associated disease. Herein, we summarize the current status of the role of tryptophan and phenylalanine metabolism in HIV disease and discuss how inflammatory stress-associated dysregulation of amino acid metabolism may be part of the pathophysiology of common HIV-associated neuropsychiatric conditions.

  3. Social Capital is Associated With Late HIV Diagnosis: An Ecological Analysis.

    Science.gov (United States)

    Ransome, Yusuf; Galea, Sandro; Pabayo, Roman; Kawachi, Ichiro; Braunstein, Sarah; Nash, Denis

    2016-10-01

    Late HIV diagnosis is associated with higher medical costs, early mortality among individuals, and HIV transmission in the population. Even under optimal configurations of stable or declining HIV incidence and increase in HIV case findings, no change in proportion of late HIV diagnosis is projected after year 2019. We investigated the association among social capital, gender, and late HIV diagnosis. We conduct ecological analyses (ZIP code, N = 166) using negative binomial regression of gender-specific rates of late HIV diagnoses (an AIDS defining illness or a CD4 count ≤200 cell/μL within 12 months of a new HIV diagnosis) in 2005 and 2006 obtained from the New York City HIV Surveillance Registry, and social capital indicators (civic engagement, political participation, social cohesion, and informal social control) from the New York Social Indicators Survey, 2004. Overall, low to high political participation and social cohesion corresponded with significant (P social control [RR = 0.67, 95% CI: (0.48 to 0.93)] among men only and moderate social cohesion [RR = 0.71, 95% CI: (0.55 to 0.92)] among women only were associated with the outcome adjusting for social fragmentation, income inequality, and racial composition. The magnitude of association between social capital and late HIV diagnosis varies by gender and by social capital indicator.

  4. Engineering HIV-1-resistant T-cells from short-hairpin RNA-expressing hematopoietic stem/progenitor cells in humanized BLT mice.

    Directory of Open Access Journals (Sweden)

    Gene-Errol E Ringpis

    Full Text Available Down-regulation of the HIV-1 coreceptor CCR5 holds significant potential for long-term protection against HIV-1 in patients. Using the humanized bone marrow/liver/thymus (hu-BLT mouse model which allows investigation of human hematopoietic stem/progenitor cell (HSPC transplant and immune system reconstitution as well as HIV-1 infection, we previously demonstrated stable inhibition of CCR5 expression in systemic lymphoid tissues via transplantation of HSPCs genetically modified by lentiviral vector transduction to express short hairpin RNA (shRNA. However, CCR5 down-regulation will not be effective against existing CXCR4-tropic HIV-1 and emergence of resistant viral strains. As such, combination approaches targeting additional steps in the virus lifecycle are required. We screened a panel of previously published shRNAs targeting highly conserved regions and identified a potent shRNA targeting the R-region of the HIV-1 long terminal repeat (LTR. Here, we report that human CD4(+ T-cells derived from transplanted HSPC engineered to co-express shRNAs targeting CCR5 and HIV-1 LTR are resistant to CCR5- and CXCR4- tropic HIV-1-mediated depletion in vivo. Transduction with the combination vector suppressed CXCR4- and CCR5- tropic viral replication in cell lines and peripheral blood mononuclear cells in vitro. No obvious cytotoxicity or interferon response was observed. Transplantation of combination vector-transduced HSPC into hu-BLT mice resulted in efficient engraftment and subsequent stable gene marking and CCR5 down-regulation in human CD4(+ T-cells within peripheral blood and systemic lymphoid tissues, including gut-associated lymphoid tissue, a major site of robust viral replication, for over twelve weeks. CXCR4- and CCR5- tropic HIV-1 infection was effectively inhibited in hu-BLT mouse spleen-derived human CD4(+ T-cells ex vivo. Furthermore, levels of gene-marked CD4(+ T-cells in peripheral blood increased despite systemic infection with either

  5. Audience reactions and receptivity to HIV prevention message concepts for people living with HIV.

    Science.gov (United States)

    Uhrig, Jennifer D; Bann, Carla M; Wasserman, Jill; Guenther-Grey, Carolyn; Eroğlu, Doğan

    2010-04-01

    This study measured audience reactions and receptivity to five draft HIV prevention messages developed for people living with HIV (PLWH) to inform future HIV message choice and audience targeting decisions. Our premise was that message concepts that receive wide audience appeal constitute a strong starting point for designing future HIV prevention messages, program activities, and health communication and marketing campaigns for PLWH. The majority of participants indicated agreement with evaluative statements that expressed favorable attitudes toward all five of the message concepts we evaluated. Participants gave the lowest approval to the message promoting sero-sorting. Sociodemographic characteristics played less of a role in predicting differences in message perceptions than attitudes, beliefs and sexual behavior. The general appeal for these messages is encouraging given that messages were expressed in plain text without the support of other creative elements that are commonly used in message execution. These results confirm the utility of systematic efforts to generate and screen message concepts prior to large-scale testing.

  6. HIV-1 gp120 Upregulates Brain-Derived Neurotrophic Factor (BDNF) Expression in BV2 Cells via the Wnt/β-Catenin Signaling Pathway.

    Science.gov (United States)

    Wang, Yongdi; Liao, Jinxu; Tang, Shao-Jun; Shu, Jianhong; Zhang, Wenping

    2017-06-01

    HIV-1 gp120 plays a critical role in the pathogenesis of HIV-associated pain, but the underlying molecular mechanisms are incompletely understood. This study aims to determine the effect and possible mechanism of HIV-1 gp120 on BDNF expression in BV2 cells (a murine-derived microglial cell line). We observed that gp120 (10 ng/ml) activated BV2 cells in cultures and upregulated proBDNF/mBDNF. Furthermore, gp120-treated BV2 also accumulated Wnt3a and β-catenin, suggesting the activation of the Wnt/β-catenin pathway. We demonstrated that activation of the pathway by Wnt3a upregulated BDNF expression. In contrast, inhibition of the Wnt/β-catenin pathway by either DKK1 or IWR-1 attenuated BDNF upregulation induced by gp120 or Wnt3a. These findings collectively suggest that gp120 stimulates BDNF expression in BV2 cells via the Wnt/β-catenin signaling pathway.

  7. Upregulation of innate antiviral restricting factor expression in the cord blood and decidual tissue of HIV-infected mothers.

    Science.gov (United States)

    Pereira, Nátalli Zanete; Cardoso, Elaine Cristina; Oliveira, Luanda Mara da Silva; de Lima, Josenilson Feitosa; Branco, Anna Cláudia Calvielli Castelo; Ruocco, Rosa Maria de Souza Aveiro; Zugaib, Marcelo; de Oliveira Filho, João Bosco; Duarte, Alberto José da Silva; Sato, Maria Notomi

    2013-01-01

    Programs for the prevention of mother-to-child transmission of HIV have reduced the transmission rate of perinatal HIV infection and have thereby increased the number of HIV-exposed uninfected (HEU) infants. Natural immunity to HIV-1 infection in both mothers and newborns needs to be further explored. In this study, we compared the expression of antiviral restricting factors in HIV-infected pregnant mothers treated with antiretroviral therapy (ART) in pregnancy (n=23) and in cord blood (CB) (n=16), placental tissues (n=10-13) and colostrum (n=5-6) samples and compared them to expression in samples from uninfected (UN) pregnant mothers (n=21). Mononuclear cells (MNCs) were prepared from maternal and CB samples following deliveries by cesarean section. Maternal (decidua) and fetal (chorionic villus) placental tissues were obtained, and colostrum was collected 24 h after delivery. The mRNA and protein expression levels of antiviral factors were then evaluated. We observed a significant increase in the mRNA expression levels of antiviral factors in MNCs from HIV-infected mothers and CB, including the apolipoprotein B mRNA-editing enzyme 3G (A3G), A3F, tripartite motif family-5α (TRIM-5α), TRIM-22, myxovirus resistance protein A (MxA), stimulator of interferon (IFN) genes (STING) and IFN-β, compared with the levels detected in uninfected (UN) mother-CB pairs. Moreover, A3G transcript and protein levels and α-defensin transcript levels were decreased in the decidua of HIV-infected mothers. Decreased TRIM-5α protein levels in the villi and increased STING mRNA expression in both placental tissues were also observed in HIV-infected mothers compared with uninfected (UN) mothers. Additionally, colostrum cells from infected mothers showed increased tetherin and IFN-β mRNA levels and CXCL9 protein levels. The data presented here indicate that antiviral restricting factor expression can be induced in utero in HIV-infected mothers. Future studies are warranted to determine

  8. Ectopic expression of anti-HIV-1 shRNAs protects CD8{sup +} T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Kamata, Masakazu, E-mail: masa3k@ucla.edu [Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Kim, Patrick Y. [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Ng, Hwee L. [Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Ringpis, Gene-Errol E.; Kranz, Emiko; Chan, Joshua; O' Connor, Sean [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Yang, Otto O. [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); UCLA AIDS Institute, Los Angeles, CA (United States); AIDS Healthcare Foundation, Los Angeles, CA (United States); Chen, Irvin S.Y. [Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); UCLA AIDS Institute, Los Angeles, CA (United States)

    2015-07-31

    Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients. We hypothesize that ectopic expression of CD4ζ on CD8{sup +} T cells renders them susceptible to HIV-1 infection, resulting in poor survival of those cells. To test this possibility, highly purified CD8{sup +} T cells were genetically modified with a CD4ζ-encoding lentiviral vector and infected with HIV-1. CD8{sup +} T cells were vulnerable to HIV-1 infection upon expression of CD4ζ as evidenced by elevated levels of p24{sup Gag} in cells and culture supernatants. Concurrently, the number of CD4ζ-modified CD8{sup +} T cells was reduced relative to control cells upon HIV-1 infection. To protect these cells from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed by our group together with CD4ζ. This combination vector was able to suppress HIV-1 infection without impairing HIV-1-dependent effector activities of CD4ζ. In addition, the number of CD4ζ-modified CD8{sup +} T cells maintained similar levels to that of the control even under HIV-1 infection. These results suggest that protecting CD4ζ-modified CD8{sup +} T cells from HIV-1 infection is required for prolonged HIV-1-specific immune surveillance. - Highlights: • Ectopic expression of CD4ζ CAR in CD8{sup +} T cells renders them susceptible to HIV-1 infection. • Co-expression of two anti-HIV-1 shRNAs protects CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection. • Protecting CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection suppresses its cytopathic effect.

  9. The HIV-1 Tat protein modulates CD4 expression in human T cells through the induction of miR-222.

    Science.gov (United States)

    Orecchini, Elisa; Doria, Margherita; Michienzi, Alessandro; Giuliani, Erica; Vassena, Lia; Ciafrè, Silvia Anna; Farace, Maria Giulia; Galardi, Silvia

    2014-01-01

    Several cellular microRNAs show substantial changes in expression during HIV-1 infection and their active role in the viral life cycle is progressively emerging. In the present study, we found that HIV-1 infection of Jurkat T cells significantly induces the expression of miR-222. We show that this induction depends on HIV-1 Tat protein, which is able to increase the transcriptional activity of NFkB on miR-222 promoter. Moreover, we demonstrate that miR-222 directly targets CD4, a key receptor for HIV-1, thus reducing its expression. We propose that Tat, by inducing miR-222 expression, complements the CD4 downregulation activity exerted by other viral proteins (i.e., Nef, Vpu, and Env), and we suggest that this represents a novel mechanism through which HIV-1 efficiently represses CD4 expression in infected cells.

  10. Menopausal symptoms and associated factors in HIV-positive women.

    Science.gov (United States)

    Lui-Filho, Jeffrey F; Valadares, Ana Lúcia R; Gomes, Debora de C; Amaral, Eliana; Pinto-Neto, Aarão M; Costa-Paiva, Lúcia

    2013-10-01

    To evaluate menopausal symptoms and their associated factors in HIV-positive women. A cross-sectional study was conducted with 537 women of 40-60 years of age, 273 of whom were HIV-positive and 264 HIV-negative. The women were interviewed to obtain data on their sociodemographic characteristics and menopausal symptoms. The mean age of the seropositive women was 47.7±5.8 years compared to 49.8±5.3 for the seronegative women (psymptoms in the seropositive group (p=0.009), specifically hot flashes (pHIV serological status and any of the menopausal symptoms. In this study, after controlling for confounding variables, HIV infection was not found to be associated with vasomotor, genitourinary or psychological symptoms or with insomnia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Cellular Profile and Expression of Immunologic Markers in Chronic Apical Periodontitis from HIV-infected Patients Undergoing Highly Active Antiretroviral Therapy.

    Science.gov (United States)

    Gama, Túlio Gustavo Veiga; Pires, Fabio Ramoa; Armada, Luciana; Gonçalves, Lucio Souza

    2016-06-01

    This study tested the hypothesis that the inflammatory cell profile (CD3-, CD4-, CD8-, CD20-, and CD68-positive cells) and the expression of immunologic markers (tumor necrosis factor α, interferon-γ, interleukin-6, and interleukin-18) in chronic apical periodontitis are the same between non-HIV-infected patients and HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Thirty-four surgically excised chronic apical periodontitis lesions were sampled from 34 patients (17 HIV-infected and 17 non-HIV-infected). The lesions were extracted from teeth with no previous endodontic treatment. All HIV-infected patients were undergoing HAART. The specimens were submitted to histopathologic and immunohistochemical analyses by using an optical microscope. Immunoexpression was graded into 2 levels, focal to weak and moderate to strong. The χ(2), Fisher exact, and Mann-Whitney tests were used to analyze all significant differences between groups. Periapical cysts represented 70.6% and 52.9% of the lesions in the HIV-infected and non-HIV-infected groups, respectively; however, no statistically significant difference was observed (P = .481). There were no statistically significant differences between groups for the inflammatory cell profile and for any of the immunologic markers (P > .05). There are no statistically significant differences of the cellular profile and expression of immunologic markers in chronic apical periodontitis between non-HIV-infected patients and HIV-infected patients undergoing HAART. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  12. Remission of HIV-associated myelopathy after highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Fernandez-Fernandez F

    2004-07-01

    Full Text Available HIV-associated myelopathy is the leading cause of spinal cord disease in HIV-infected patients. Typically, it affects individuals with low CD4 T cell counts, presenting with slowly progressive spastic paraparesis associated with dorsal column sensory loss as well as urinary disturbances. Other aetiologies must be first ruled out before establishing the diagnosis. We report here the case of a 37-year-old woman with advanced HIV disease, who developed HIV-associated myelopathy. The patient showed a gradual improvement after beginning with highly active antiretroviral therapy and, finally, she achieved a complete functional recovery. In addition, neuroimaging and neurophysiological tests normalized.

  13. Quantitative analysis of differentially expressed saliva proteins in human immunodeficiency virus type 1 (HIV-1) infected individuals

    International Nuclear Information System (INIS)

    Zhang, Nawei; Zhang, Zhenyu; Feng, Shan; Wang, Qingtao; Malamud, Daniel; Deng, Haiteng

    2013-01-01

    Highlights: ► A high-throughput method for profiling and quantification of the differentially expressed proteins in saliva samples was developed. ► Identified that DMBT1, S100A7, S100A8, S100A9 and alpha defensin were up-regulated in saliva from HIV-1 seropositive patients. ► Established analytical strategies are translatable to the clinical setting. -- Abstract: In the present study, we have established a new methodology to analyze saliva proteins from HIV-1-seropositive patients before highly active antiretroviral therapy (HAART) and seronegative controls. A total of 593 and 601 proteins were identified in the pooled saliva samples from 5 HIV-1 subjects and 5 controls, respectively. Forty-one proteins were found to be differentially expressed. Bioinformatic analysis of differentially expressed salivary proteins showed an increase of antimicrobial proteins and decrease of protease inhibitors upon HIV-1 infection. To validate some of these differentially expressed proteins, a high-throughput quantitation method was established to determine concentrations of 10 salivary proteins in 40 individual saliva samples from 20 seropositive patients before HAART and 20 seronegative subjects. This method was based on limited protein separation within the zone of the stacking gel of the 1D SDS PAGE and using isotope-coded synthetic peptides as internal standards. The results demonstrated that a combination of protein profiling and targeted quantitation is an efficient method to identify and validate differentially expressed salivary proteins. Expression levels of members of the calcium-binding S100 protein family and deleted in malignant brain tumors 1 protein (DMBT1) were up-regulated while that of Mucin 5B was down-regulated in HIV-1 seropositive saliva samples, which may provide new perspectives for monitoring HIV-infection and understanding the mechanism of HIV-1 infectivity

  14. Quantitative analysis of differentially expressed saliva proteins in human immunodeficiency virus type 1 (HIV-1) infected individuals

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Nawei; Zhang, Zhenyu [Beijing Chaoyang Hospital Affiliated Capital Medical University, Beijing (China); Feng, Shan [MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing (China); Wang, Qingtao [Beijing Chaoyang Hospital Affiliated Capital Medical University, Beijing (China); Malamud, Daniel [NYU College of Dentistry, 345 East 24th Street, New York, NY 10010 (United States); Deng, Haiteng, E-mail: dht@mail.tsinghua.edu.cn [MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing (China)

    2013-04-24

    Highlights: ► A high-throughput method for profiling and quantification of the differentially expressed proteins in saliva samples was developed. ► Identified that DMBT1, S100A7, S100A8, S100A9 and alpha defensin were up-regulated in saliva from HIV-1 seropositive patients. ► Established analytical strategies are translatable to the clinical setting. -- Abstract: In the present study, we have established a new methodology to analyze saliva proteins from HIV-1-seropositive patients before highly active antiretroviral therapy (HAART) and seronegative controls. A total of 593 and 601 proteins were identified in the pooled saliva samples from 5 HIV-1 subjects and 5 controls, respectively. Forty-one proteins were found to be differentially expressed. Bioinformatic analysis of differentially expressed salivary proteins showed an increase of antimicrobial proteins and decrease of protease inhibitors upon HIV-1 infection. To validate some of these differentially expressed proteins, a high-throughput quantitation method was established to determine concentrations of 10 salivary proteins in 40 individual saliva samples from 20 seropositive patients before HAART and 20 seronegative subjects. This method was based on limited protein separation within the zone of the stacking gel of the 1D SDS PAGE and using isotope-coded synthetic peptides as internal standards. The results demonstrated that a combination of protein profiling and targeted quantitation is an efficient method to identify and validate differentially expressed salivary proteins. Expression levels of members of the calcium-binding S100 protein family and deleted in malignant brain tumors 1 protein (DMBT1) were up-regulated while that of Mucin 5B was down-regulated in HIV-1 seropositive saliva samples, which may provide new perspectives for monitoring HIV-infection and understanding the mechanism of HIV-1 infectivity.

  15. Prediction of the binding mode and resistance profile for a dual-target pyrrolyl diketo acid scaffold against HIV-1 integrase and reverse-transcriptase-associated ribonuclease H.

    Science.gov (United States)

    Yang, Fengyuan; Zheng, Guoxun; Fu, Tingting; Li, Xiaofeng; Tu, Gao; Li, Ying Hong; Yao, Xiaojun; Xue, Weiwei; Zhu, Feng

    2018-06-27

    The rapid emergence of drug-resistant variants is one of the most common causes of highly active antiretroviral therapeutic (HAART) failure in patients infected with HIV-1. Compared with the existing HAART, the recently developed pyrrolyl diketo acid scaffold targeting both HIV-1 integrase (IN) and reverse transcriptase-associated ribonuclease H (RNase H) is an efficient approach to counteract the failure of anti-HIV treatment due to drug resistance. However, the binding mode and potential resistance profile of these inhibitors with important mechanistic principles remain poorly understood. To address this issue, an integrated computational method was employed to investigate the binding mode of inhibitor JMC6F with HIV-1 IN and RNase H. By using per-residue binding free energy decomposition analysis, the following residues: Asp64, Thr66, Leu68, Asp116, Tyr143, Gln148 and Glu152 in IN, Asp443, Glu478, Trp536, Lys541 and Asp549 in RNase H were identified as key residues for JMC6F binding. And then computational alanine scanning was carried to further verify the key residues. Moreover, the resistance profile of the currently known major mutations in HIV-1 IN and 2 mutations in RNase H against JMC6F was predicted by in silico mutagenesis studies. The results demonstrated that only three mutations in HIV-1 IN (Y143C, Q148R and N155H) and two mutations in HIV-1 RNase H (Y501R and Y501W) resulted in a reduction of JMC6F potency, thus indicating their potential role in providing resistance to JMC6F. These data provided important insights into the binding mode and resistance profile of the inhibitors with a pyrrolyl diketo acid scaffold in HIV-1 IN and RNase H, which would be helpful for the development of more effective dual HIV-1 IN and RNase H inhibitors.

  16. Maternal HIV Serostatus, Mother–Daughter Sexual Risk Communication and Adolescent HIV Risk Beliefs and Intentions

    Science.gov (United States)

    Hutchinson, M. Katherine; Duan, Lei; Jemmott, Loretta S.

    2012-01-01

    Daughters of HIV-positive women are often exposed to the same factors that placed their mothers at risk. This cross-sectional study (N = 176 dyads) examined HIV status, parent-teen sexual risk communication (PTSRC), and daughters’ abstinence and condom use beliefs and intentions. Maternal HIV status was not associated with PTSRC. Path analyses show that maternal depression was associated with PTSRC behavioral and normative beliefs; relationship satisfaction was associated with PTSRC normative and control beliefs. Control beliefs were solely predictive of maternal PTSRC intention. PTSRC was associated with adolescent behavioral and normative beliefs. Abstinence beliefs were associated with abstinence intentions; condom beliefs were associated with condom use intentions. Relationship satisfaction was associated with adolescent control beliefs about both abstinence and condom use. There is a need for interventions that help HIV-positive mothers recognize their daughter’s HIV risk and provide them with relationship building and parent process skills to help reduce these risks. PMID:22677973

  17. Maternal HIV serostatus, mother-daughter sexual risk communication and adolescent HIV risk beliefs and intentions.

    Science.gov (United States)

    Cederbaum, Julie A; Hutchinson, M Katherine; Duan, Lei; Jemmott, Loretta S

    2013-09-01

    Daughters of HIV-positive women are often exposed to the same factors that placed their mothers at risk. This cross-sectional study (N = 176 dyads) examined HIV status, parent-teen sexual risk communication (PTSRC), and daughters' abstinence and condom use beliefs and intentions. Maternal HIV status was not associated with PTSRC. Path analyses show that maternal depression was associated with PTSRC behavioral and normative beliefs; relationship satisfaction was associated with PTSRC normative and control beliefs. Control beliefs were solely predictive of maternal PTSRC intention. PTSRC was associated with adolescent behavioral and normative beliefs. Abstinence beliefs were associated with abstinence intentions; condom beliefs were associated with condom use intentions. Relationship satisfaction was associated with adolescent control beliefs about both abstinence and condom use. There is a need for interventions that help HIV-positive mothers recognize their daughter's HIV risk and provide them with relationship building and parent process skills to help reduce these risks.

  18. Depression and anxiety mediate perceived social support to predict health-related quality of life in pregnant women living with HIV.

    Science.gov (United States)

    Xiaowen, Wang; Guangping, Guo; Ling, Zhou; Jiarui, Zheng; Xiumin, Liang; Zhaoqin, Li; Hongzhuan, Luo; Yuyan, Yang; Liyuan, Yang; Lin, Lu

    2018-04-01

    Pregnant women living with HIV represent one of the most high-priority groups for HIV treatment and health assessment. Although social support has been shown to be a protective factor for improved health-related quality of life (HRQoL), and depression and anxiety have been identified as two major causes of psychological distress among people living with HIV, it is still unclear how social support, anxiety, and depression interact to influence HRQoL. The objective of our study was to demonstrate the nature of predictors, direct effects and mediator effects among social support, anxiety, depression symptoms and HRQoL in pregnant women living with HIV. We investigated a total of 101 pregnant women living with HIV in Yunnan province in China from April 2016 to June 2016. All participants completed the Social Support Rating Scale (SSRS), the Chinese version of the Hospital Anxiety and Depression Scales (HADS) and Quality of Life instruments (EuroQoL Five Dimensions Questionnaire, EQ-5D). The relationships between the variables were examined by Pearson's or Spearman's correlation analysis. Predictor effects were tested using separate multiple regressions, controlling for demographic variables and HIV diagnosis variables. Direct and mediation effects of social support on HRQoL were tested using a structural equation model (SEM). Anxiety and depression symptoms were negatively correlated with subjective social support, support utilization, social support and HRQoL. Social support significantly predicted better HRQoL, and anxiety and depression symptoms significantly predicted poorer HRQoL. Anxiety and depression symptoms partially mediated the associations between social support and HRQoL. Anxiety and depression symptoms completely mediated the associations of objective support and support utilization with HRQoL. Interventions to improve HRQoL in pregnant women living with HIV must consider the mediation effect of anxiety and depression symptoms on the association between

  19. Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy

    Directory of Open Access Journals (Sweden)

    Dobson Wendy

    2011-06-01

    Full Text Available Abstract Background RNA processing plays a critical role in the replication of HIV-1, regulated in part through the action of host SR proteins. To explore the impact of modulating SR protein activity on virus replication, the effect of increasing or inhibiting the activity of the Cdc2-like kinase (CLK family of SR protein kinases on HIV-1 expression and RNA processing was examined. Results Despite their high homology, increasing individual CLK expression had distinct effects on HIV-1, CLK1 enhancing Gag production while CLK2 inhibited the virus. Parallel studies on the anti-HIV-1 activity of CLK inhibitors revealed a similar discrepant effect on HIV-1 expression. TG003, an inhibitor of CLK1, 2 and 4, had no effect on viral Gag synthesis while chlorhexidine, a CLK2, 3 and 4 inhibitor, blocked virus production. Chlorhexidine treatment altered viral RNA processing, decreasing levels of unspliced and single spliced viral RNAs, and reduced Rev accumulation. Subsequent experiments in the context of HIV-1 replication in PBMCs confirmed the capacity of chlorhexidine to suppress virus replication. Conclusions Together, these findings establish that HIV-1 RNA processing can be targeted to suppress virus replication as demonstrated by manipulating individual CLK function and identified chlorhexidine as a lead compound in the development of novel anti-viral therapies.

  20. Interferon-α Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms.

    Directory of Open Access Journals (Sweden)

    Michael S Harper

    Full Text Available HIV-1 is transmitted primarily across mucosal surfaces and rapidly spreads within the intestinal mucosa during acute infection. The type I interferons (IFNs likely serve as a first line of defense, but the relative expression and antiviral properties of the 12 IFNα subtypes against HIV-1 infection of mucosal tissues remain unknown. Here, we evaluated the expression of all IFNα subtypes in HIV-1-exposed plasmacytoid dendritic cells by next-generation sequencing. We then determined the relative antiviral potency of each IFNα subtype ex vivo using the human intestinal Lamina Propria Aggregate Culture model. IFNα subtype transcripts from the centromeric half of the IFNA gene complex were highly expressed in pDCs following HIV-1 exposure. There was an inverse relationship between IFNA subtype expression and potency. IFNα8, IFNα6 and IFNα14 were the most potent in restricting HIV-1 infection. IFNα2, the clinically-approved subtype, and IFNα1 were both highly expressed but exhibited relatively weak antiviral activity. The relative potencies correlated with binding affinity to the type I IFN receptor and the induction levels of HIV-1 restriction factors Mx2 and Tetherin/BST-2 but not APOBEC3G, F and D. However, despite the lack of APOBEC3 transcriptional induction, the higher relative potency of IFNα8 and IFNα14 correlated with stronger inhibition of virion infectivity, which is linked to deaminase-independent APOBEC3 restriction activity. By contrast, both potent (IFNα8 and weak (IFNα1 subtypes significantly induced HIV-1 GG-to-AG hypermutation. The results unravel non-redundant functions of the IFNα subtypes against HIV-1 infection, with strong implications for HIV-1 mucosal immunity, viral evolution and IFNα-based functional cure strategies.

  1. Modeling HIV-associated neurocognitive disorders in mice: new approaches in the changing face of HIV neuropathogenesis.

    Science.gov (United States)

    Jaeger, Laura B; Nath, Avindra

    2012-05-01

    It is well established that infection with the human immunodeficiency virus (HIV) leads to immune suppression. Less well known is the fact that long-term, progressive HIV disease is associated with the development of cognitive deficits. Since the introduction of combined antiretroviral therapy (cART), the clinical presentation of HIV infection has evolved into a chronic illness with very low levels of viral replication and chronic immune activation, with compliant affected individuals surviving for decades with a high quality of life. Despite these advances, many HIV-infected individuals develop some degree of neurodegeneration and cognitive impairment. The underlying pathophysiological mechanisms are not well understood, and there are no effective treatments. Thus, there is an unmet need for animal models that enable the study of HIV-associated neurocognitive disorders (HAND) and the testing of new therapeutic approaches to combat them. Here, we review the pros and cons of existing mouse models of HIV infection for addressing these aims and propose a detailed strategy for developing a new mouse model of HIV infection.

  2. Modeling HIV-associated neurocognitive disorders in mice: new approaches in the changing face of HIV neuropathogenesis

    Directory of Open Access Journals (Sweden)

    Laura B. Jaeger

    2012-05-01

    Full Text Available It is well established that infection with the human immunodeficiency virus (HIV leads to immune suppression. Less well known is the fact that long-term, progressive HIV disease is associated with the development of cognitive deficits. Since the introduction of combined antiretroviral therapy (cART, the clinical presentation of HIV infection has evolved into a chronic illness with very low levels of viral replication and chronic immune activation, with compliant affected individuals surviving for decades with a high quality of life. Despite these advances, many HIV-infected individuals develop some degree of neurodegeneration and cognitive impairment. The underlying pathophysiological mechanisms are not well understood, and there are no effective treatments. Thus, there is an unmet need for animal models that enable the study of HIV-associated neurocognitive disorders (HAND and the testing of new therapeutic approaches to combat them. Here, we review the pros and cons of existing mouse models of HIV infection for addressing these aims and propose a detailed strategy for developing a new mouse model of HIV infection.

  3. The HIV-1 Tat protein modulates CD4 expression in human T cells through the induction of miR-222

    Science.gov (United States)

    Orecchini, Elisa; Doria, Margherita; Michienzi, Alessandro; Giuliani, Erica; Vassena, Lia; Ciafrè, Silvia Anna; Farace, Maria Giulia; Galardi, Silvia

    2014-01-01

    Several cellular microRNAs show substantial changes in expression during HIV-1 infection and their active role in the viral life cycle is progressively emerging. In the present study, we found that HIV-1 infection of Jurkat T cells significantly induces the expression of miR-222. We show that this induction depends on HIV-1 Tat protein, which is able to increase the transcriptional activity of NFkB on miR-222 promoter. Moreover, we demonstrate that miR-222 directly targets CD4, a key receptor for HIV-1, thus reducing its expression. We propose that Tat, by inducing miR-222 expression, complements the CD4 downregulation activity exerted by other viral proteins (i.e., Nef, Vpu, and Env), and we suggest that this represents a novel mechanism through which HIV-1 efficiently represses CD4 expression in infected cells. PMID:24717285

  4. gCUP: rapid GPU-based HIV-1 co-receptor usage prediction for next-generation sequencing.

    Science.gov (United States)

    Olejnik, Michael; Steuwer, Michel; Gorlatch, Sergei; Heider, Dominik

    2014-11-15

    Next-generation sequencing (NGS) has a large potential in HIV diagnostics, and genotypic prediction models have been developed and successfully tested in the recent years. However, albeit being highly accurate, these computational models lack computational efficiency to reach their full potential. In this study, we demonstrate the use of graphics processing units (GPUs) in combination with a computational prediction model for HIV tropism. Our new model named gCUP, parallelized and optimized for GPU, is highly accurate and can classify >175 000 sequences per second on an NVIDIA GeForce GTX 460. The computational efficiency of our new model is the next step to enable NGS technologies to reach clinical significance in HIV diagnostics. Moreover, our approach is not limited to HIV tropism prediction, but can also be easily adapted to other settings, e.g. drug resistance prediction. The source code can be downloaded at http://www.heiderlab.de d.heider@wz-straubing.de. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052.

    Directory of Open Access Journals (Sweden)

    Philip J Palumbo

    Full Text Available Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART. We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM assay was used to analyze baseline (pre-treatment HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008. The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

  6. Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052.

    Science.gov (United States)

    Palumbo, Philip J; Wilson, Ethan A; Piwowar-Manning, Estelle; McCauley, Marybeth; Gamble, Theresa; Kumwenda, Newton; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James G; Hosseinipour, Mina C; Melo, Marineide G; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H; Fogel, Jessica M

    2017-01-01

    Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

  7. No evidence of association between HIV-1 and malaria in populations with low HIV-1 prevalence.

    Directory of Open Access Journals (Sweden)

    Diego F Cuadros

    Full Text Available The geographic overlap between HIV-1 and malaria has generated much interest in their potential interactions. A variety of studies have evidenced a complex HIV-malaria interaction within individuals and populations that may have dramatic effects, but the causes and implications of this co-infection at the population level are still unclear. In a previous publication, we showed that the prevalence of malaria caused by the parasite Plasmodium falciparum is associated with HIV infection in eastern sub-Saharan Africa. To complement our knowledge of the HIV-malaria co-infection, the objective of this work was to assess the relationship between malaria and HIV prevalence in the western region of sub-Saharan Africa.Population-based cross-sectional data were obtained from the HIV/AIDS Demographic and Health Surveys conducted in Burkina Faso, Ghana, Guinea, Mali, Liberia and Cameroon, and the malaria atlas project. Using generalized linear mixed models, we assessed the relationship between HIV-1 and Plasmodium falciparum parasite rate (PfPR adjusting for important socio-economic and biological cofactors. We found no evidence that individuals living in areas with stable malaria transmission (PfPR>0.46 have higher odds of being HIV-positive than individuals who live in areas with PfPR≤0.46 in western sub-Saharan Africa (estimated odds ratio 1.14, 95% confidence interval 0.86-1.50. In contrast, the results suggested that PfPR was associated with being infected with HIV in Cameroon (estimated odds ratio 1.56, 95% confidence interval 1.23-2.00.Contrary to our previous research on eastern sub-Saharan Africa, this study did not identify an association between PfPR and infection with HIV in western sub-Saharan Africa, which suggests that malaria might not play an important role in the spread of HIV in populations where the HIV prevalence is low. Our work highlights the importance of understanding the epidemiologic effect of co-infection and the relevant

  8. Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset.

    Directory of Open Access Journals (Sweden)

    Mickaël J Ploquin

    2016-08-01

    Full Text Available Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort, as well as during controlled and uncontrolled viremia (ANRS cohorts. We also addressed IP-10 expression levels with regards to lymphoid tissues (LT and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10.

  9. Plasma levels of soluble CD14 independently predict mortality in HIV infection

    DEFF Research Database (Denmark)

    Sandler, Netanya G; Wand, Handan; Roque, Annelys

    2011-01-01

    Chronic human immunodeficiency virus (HIV) infection is associated with intestinal permeability and microbial translocation that contributes to systemic immune activation, which is an independent predictor of HIV disease progression. The association of microbial translocation with clinical outcom...

  10. Predicting hypothetical willingness to participate (WTP) in a future phase III HIV vaccine trial among high-risk adolescents.

    Science.gov (United States)

    Giocos, Georgina; Kagee, Ashraf; Swartz, Leslie

    2008-11-01

    The present study sought to determine whether the Theory of Planned Behaviour predicted stated hypothetical willingness to participate (WTP) in future Phase III HIV vaccine trials among South African adolescents. Hierarchical logistic regression analyses showed that The Theory of Planned Behaviour (TPB) significantly predicted WTP. Of all the predictors, Subjective norms significantly predicted WTP (OR = 1.19, 95% C.I. = 1.06-1.34). A stepwise logistic regression analysis revealed that Subjective Norms (OR = 1.19, 95% C.I. = 1.07-1.34) and Attitude towards participation in an HIV vaccine trial (OR = 1.32, 95% C.I. = 1.00-1.74) were significant predictors of WTP. The addition of Knowledge of HIV vaccines and HIV vaccine trials, Perceived self-risk of HIV infection, Health-promoting behaviours and Attitudes towards HIV/AIDS yielded non-significant results. These findings provide support for the Theory of Reasoned Action (TRA) and suggest that psychosocial factors may play an important role in WTP in Phase III HIV vaccine trials among adolescents.

  11. Cross-country Association of Press Freedom and LGBT freedom with prevalence of persons living with HIV: implication for global strategy against HIV/AIDS.

    Science.gov (United States)

    Chen, Xinguang; Elliott, Amy L; Wang, Shuang

    2018-01-01

    Human behaviors are affected by attitudes and beliefs, which in turn are shaped by higher-level values to which we have ascribed. In this study, we explore the relationship between two higher-level values, press freedom and LGBT freedom, and HIV infection with national data at the population level. Data were the number of persons living with HIV (PLWH, n  = 35,468,911) for 148 countries during 2011-15, press freedom index (PFI) determined by the Reporters Without Borders, and LGBT freedom index (LGBT-FI) based on laws regulating same-sex relationships and expression. PLWH prevalence (1/1000), PFI and LGBT-FI were mapped first. Multiple regression was thus used to associate the logarithm of PLWH prevalence with PFI, LGBT-FI and PFI × LGBT-FI interaction, controlling for per capita GDP and weighted by population size. Global prevalence of PLWH during 2011-15 was 0.51 per 1000 population. The prevalence showed a geographic pattern moving from high at the south and west ends of the world map to low at the north and east. Both PFI and LGBT-FI were positively associated with PLWH prevalence with a negative interaction between the two. More people are infected with HIV in countries with higher press freedom and higher LGBT freedom. Furthermore, press freedom can attenuate the positive association between levels of LGBT freedom and risk of HIV infection. This study demonstrated the urgency for and provided data supporting further research to investigate potential cultural and socioecological mechanisms underpinning the complex relationship among press freedom, LGBT freedom and HIV infection, with data collected at the individual level.

  12. Antiretroviral treatment uptake in patients with HIV associated TB ...

    African Journals Online (AJOL)

    Background. Delivery of integrated care for patients with HIV-associated TB is challenging. We assessed the uptake and timing of antiretroviral treatment (ART) among eligible patients attending a primary care service with co-located ART and TB clinics. Methods. In a retrospective cohort study, all HIV-associated TB patients ...

  13. Seroadaptive practices: association with HIV acquisition among HIV-negative men who have sex with men.

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    Snigdha Vallabhaneni

    Full Text Available Although efficacy is unknown, many men who have sex with men (MSM attempt to reduce HIV risk by adapting condom use, partner selection, or sexual position to the partner's HIV serostatus. We assessed the association of seroadaptive practices with HIV acquisition.We pooled data on North American MSM from four longitudinal HIV-prevention studies. Sexual behaviors reported during each six-month interval were assigned sequentially to one of six mutually exclusive risk categories: (1 no unprotected anal intercourse (UAI, (2 having a single negative partner, (3 being an exclusive top (only insertive anal sex, (4 serosorting (multiple partners, all HIV negative, (5 seropositioning (only insertive anal sex with potentially discordant partners, and (6 UAI with no seroadaptive practices. HIV antibody testing was conducted at the end of each interval. We used Cox models to evaluate the independent association of each category with HIV acquisition, controlling for number of partners, age, race, drug use, and intervention assignment. 12,277 participants contributed to 60,162 six-month intervals with 663 HIV seroconversions. No UAI was reported in 47.4% of intervals, UAI with some seroadaptive practices in 31.8%, and UAI with no seroadaptive practices in 20.4%. All seroadaptive practices were associated with a lower risk, compared to UAI with no seroadaptive practices. However, compared to no UAI, serosorting carried twice the risk (HR = 2.03, 95%CI:1.51-2.73, whereas seropositioning was similar in risk (HR = 0.85, 95%CI:0.50-1.44, and UAI with a single negative partner and as an exclusive top were both associated with a lower risk (HR = 0.56, 95%CI:0.32-0.96 and HR = 0.55, 95%CI:0.36-0.84, respectively.Seroadaptive practices appear protective when compared with UAI with no seroadaptive practices, but serosorting appears to be twice as risky as no UAI. Condom use and limiting number of partners should be advocated as first-line prevention

  14. Headache among patients with HIV disease: prevalence, characteristics, and associations.

    Science.gov (United States)

    Kirkland, Kale E; Kirkland, Karl; Many, W J; Smitherman, Todd A

    2012-03-01

    Headache is one of the most common medical complaints reported by individuals suffering from human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), but limited and conflicting data exist regarding their prevalence, prototypical characteristics, and relationship to HIV disease variables in the current era of highly active antiretroviral therapy (HAART). The aims of the present cross-sectional study were to characterize headache symptoms among patients with HIV/AIDS and to assess relations between headache and HIV/AIDS disease variables. Two hundred HIV/AIDS patients (49% female; mean age = 43.22 ± 12.30 years; 74% African American) from an internal medicine clinic and an AIDS outreach clinic were administered a structured headache diagnostic interview to assess headache characteristics and features consistent with International Classification of Headache Disorders (ICHD)-II diagnostic semiologies. They also completed 2 measures of headache-related disability. Prescribed medications, most recent cluster of differentiation (CD4) cell count, date of HIV diagnosis, possible causes of secondary headache, and other relevant medical history were obtained via review of patient medical records. One hundred seven patients (53.5%) reported headache symptoms, the large majority of which were consistent with characteristics of primary headache disorders after excluding 4 cases attributable to secondary causes. Among those who met criteria for a primary headache disorder, 88 (85.44%) met criteria for migraine, most of which fulfilled ICHD-II appendix diagnostic criteria for chronic migraine. Fifteen patients (14.56%) met criteria for episodic or chronic tension-type headache. Severity of HIV (as indicated by CD4 cell counts), but not duration of HIV or number of prescribed antiretroviral medications, was strongly associated with headache severity, frequency, and disability and also distinguished migraine from TTH. Problematic headache is highly prevalent

  15. Genome-wide admixture and association study of subclinical atherosclerosis in the Women's Interagency HIV Study (WIHS.

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    Aditi Shendre

    Full Text Available Cardiovascular disease (CVD is a major comorbidity among HIV-infected individuals. Common carotid artery intima-media thickness (cCIMT is a valid and reliable subclinical measure of atherosclerosis and is known to predict CVD. We performed genome-wide association (GWA and admixture analysis among 682 HIV-positive and 288 HIV-negative Black, non-Hispanic women from the Women's Interagency HIV study (WIHS cohort using a combined and stratified analysis approach. We found some suggestive associations but none of the SNPs reached genome-wide statistical significance in our GWAS analysis. The top GWAS SNPs were rs2280828 in the region intergenic to mediator complex subunit 30 and exostosin glycosyltransferase 1 (MED30 | EXT1 among all women, rs2907092 in the catenin delta 2 (CTNND2 gene among HIV-positive women, and rs7529733 in the region intergenic to family with sequence similarity 5, member C and regulator of G-protein signaling 18 (FAM5C | RGS18 genes among HIV-negative women. The most significant local European ancestry associations were in the region intergenic to the zinc finger and SCAN domain containing 5D gene and NADH: ubiquinone oxidoreductase complex assembly factor 1 (ZSCAN5D | NDUF1 pseudogene on chromosome 19 among all women, in the region intergenic to vomeronasal 1 receptor 6 pseudogene and zinc finger protein 845 (VN1R6P | ZNF845 gene on chromosome 19 among HIV-positive women, and in the region intergenic to the SEC23-interacting protein and phosphatidic acid phosphatase type 2 domain containing 1A (SEC23IP | PPAPDC1A genes located on chromosome 10 among HIV-negative women. A number of previously identified SNP associations with cCIMT were also observed and included rs2572204 in the ryanodine receptor 3 (RYR3 and an admixture region in the secretion-regulating guanine nucleotide exchange factor (SERGEF gene. We report several SNPs and gene regions in the GWAS and admixture analysis, some of which are common across HIV-positive and

  16. Associations of the vaginal microbiota with HIV infection, bacterial vaginosis, and demographic factors.

    Science.gov (United States)

    Chehoud, Christel; Stieh, Daniel J; Bailey, Aubrey G; Laughlin, Alice L; Allen, Shannon A; McCotter, Kerrie L; Sherrill-Mix, Scott A; Hope, Thomas J; Bushman, Frederic D

    2017-04-24

    We sought to investigate the effects of HIV infection on the vaginal microbiota and associations with treatment and demographic factors. We thus compared vaginal microbiome samples from HIV-infected (HIV+) and HIV-uninfected (HIV-) women collected at two Chicago area hospitals. We studied vaginal microbiome samples from 178 women analyzed longitudinally (n = 324 samples) and collected extensive data on clinical status and demographic factors. We used 16S rRNA gene sequencing to characterize the bacterial lineages present, then UniFrac, Shannon diversity, and other measures to compare community structure with sample metadata. Differences in microbiota measures were modest in the comparison of HIV+ and HIV- samples, in contrast to several previous studies, consistent with effective antiretroviral therapy. Proportions of healthy Lactobacillus species were not higher in HIV- patients overall, but were significantly higher when analyzed within each hospital in isolation. Rates of bacterial vaginosis were higher among African-American women and HIV+ women. Bacterial vaginosis was associated with higher frequency of HIV+. Unexpectedly, African-American women were more likely to switch bacterial vaginosis status between sampling times; switching was not associated with HIV+ status. The influence of HIV infection on the vaginal microbiome was modest for this cohort of well suppressed urban American women, consistent with effective antiretroviral therapy. HIV+ was found to be associated with bacterial vaginosis. Although bacterial vaginosis has previously been associated with HIV transmission, most of the women studied here became HIV+ many years before our test for bacterial vaginosis, thus implicating additional mechanisms linking HIV infection and bacterial vaginosis.

  17. Advanced oral HIV-associated Kaposi sarcoma with facial ...

    African Journals Online (AJOL)

    Rapidly progressive facial lymphoedoema that develops concurrently with or immediately after rapid enlargement of oral Kaposi sarcoma in human immunodeficiency virus (HIV) -seropositive persons forebodes death. Previously, we reported on three patients with HIV-associated Kaposi sarcoma who had not been ...

  18. Individual- and contextual-level factors associated with client-initiated HIV testing

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    Claudia Renata dos Santos Barros

    Full Text Available ABSTRACT: Background: Knowing the reasons for seeking HIV testing is central for HIV prevention. Despite the availability of free HIV counseling and testing in Brazil, coverage remains lacking. Methods: Survey of 4,760 respondents from urban areas was analyzed. Individual-level variables included sociodemographic characteristics; sexual and reproductive health; HIV/AIDS treatment knowledge and beliefs; being personally acquainted with a person with HIV/AIDS; and holding discriminatory ideas about people living with HIV. Contextual-level variables included the Human Development Index (HDI of the municipality; prevalence of HIV/AIDS; and availability of local HIV counseling and testing (CT services. The dependent variable was client-initiated testing. Multilevel Poisson regression models with random intercepts were used to assess associated factors. Results: Common individual-level variables among men and women included being personally acquainted with a person with HIV/AIDS and age; whereas discordant variables included those related to sexual and reproductive health and experiencing sexual violence. Among contextual-level factors, availability of CT services was variable associated with client-initiated testing among women only. The contextual-level variable “HDI of the municipality” was associated with client-initiated testing among women. Conclusion: Thus, marked gender differences in HIV testing were found, with a lack of HIV testing among married women and heterosexual men, groups that do not spontaneously seek testing.

  19. An Increase in Religiousness/Spirituality Occurs After HIV Diagnosis and Predicts Slower Disease Progression over 4 Years in People with HIV

    Science.gov (United States)

    Ironson, Gail; Stuetzle, Rick; Fletcher, Mary Ann

    2006-01-01

    BACKGROUND Most studies on religion/spirituality predicting health outcomes have been limited to church attendance as a predictor and have focused on healthy people. However, confronting a major medical crisis may be a time when people turn to the sacred. OBJECTIVE The purpose of this study was to determine the extent to which changes in spirituality/religiousness occur after HIV diagnosis and whether changes predict disease progression. DESIGN/PARTICIPANTS This longitudinal study examined the relationship between changes in spirituality/religiousness from before with after the diagnosis of HIV, and disease progression (CD4 and viral load [VL] every 6 months) over 4 years in 100 people with HIV. Measures included change in religiousness/spirituality after diagnosis of HIV, religiousness/spirituality at various times in one’s life, church attendance, depression, hopelessness, optimism, coping (avoidant, proactive), social support, CD4/VL, and health behaviors. RESULTS Forty-five percent of the sample showed an increase in religiousness/spirituality after the diagnosis of HIV, 42% remained the same, and 13% decreased. People reporting an increase in spirituality/religiousness after the diagnosis had significantly greater preservation of CD4 cells over the 4-year period, as well as significantly better control of VL. Results were independent of (i.e., held even after controlling for) church attendance and initial disease status (CD4/VL), medication at every time point, age, gender, race, education, health behaviors (adherence, risky sex, alcohol, cocaine), depression, hopelessness, optimism, coping (avoidant, proactive), and social support. CONCLUSIONS There is an increase in spirituality/religiousness after HIV diagnosis, and this increase predicts slower disease progression; medical personnel should be aware of its potential importance. PMID:17083503

  20. Drug-induced liver injury associated with HIV medications.

    Science.gov (United States)

    Jain, Mamta K

    2007-08-01

    Antiretroviral therapy (ART) for HIV infection frequently has been associated with elevated liver enzyme levels. Determining the cause of elevated liver enzyme levels in patients who have HIV is difficult because ART usually consists of three different drugs, patients may be taking additional hepatotoxic medications and patients who have HIV often suffer from other liver diseases. Several agents, however, are recognized as having noteworthy and specific patterns of toxicity. This article reviews the different HIV drug classes, incidence of elevated liver enzyme values by class and by individual drug, risk factors, specific toxicities, and possible mechanisms of injury.

  1. Interferon-α regulates glutaminase 1 promoter through STAT1 phosphorylation: relevance to HIV-1 associated neurocognitive disorders.

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    Lixia Zhao

    Full Text Available HIV-1 associated neurocognitive disorders (HAND develop during progressive HIV-1 infection and affect up to 50% of infected individuals. Activated microglia and macrophages are critical cell populations that are involved in the pathogenesis of HAND, which is specifically related to the production and release of various soluble neurotoxic factors including glutamate. In the central nervous system (CNS, glutamate is typically derived from glutamine by mitochondrial enzyme glutaminase. Our previous study has shown that glutaminase is upregulated in HIV-1 infected monocyte-derived-macrophages (MDM and microglia. However, how HIV-1 leads to glutaminase upregulation, or how glutaminase expression is regulated in general, remains unclear. In this study, using a dual-luciferase reporter assay system, we demonstrated that interferon (IFN α specifically activated the glutaminase 1 (GLS1 promoter. Furthermore, IFN-α treatment increased signal transducer and activator of transcription 1 (STAT1 phosphorylation and glutaminase mRNA and protein levels. IFN-α stimulation of GLS1 promoter activity correlated to STAT1 phosphorylation and was reduced by fludarabine, a chemical that inhibits STAT1 phosphorylation. Interestingly, STAT1 was found to directly bind to the GLS1 promoter in MDM, an effect that was dependent on STAT1 phosphorylation and significantly enhanced by IFN-α treatment. More importantly, HIV-1 infection increased STAT1 phosphorylation and STAT1 binding to the GLS1 promoter, which was associated with increased glutamate levels. The clinical relevance of these findings was further corroborated with investigation of post-mortem brain tissues. The glutaminase C (GAC, one isoform of GLS1 mRNA levels in HIV associated-dementia (HAD individuals correlate with STAT1 (p<0.01, IFN-α (p<0.05 and IFN-β (p<0.01. Together, these data indicate that both HIV-1 infection and IFN-α treatment increase glutaminase expression through STAT1 phosphorylation and

  2. Regulation of HIV receptor expression in cervical epithelial cells by ...

    African Journals Online (AJOL)

    Background. Sexually transmitted infections (STIs) caused by the Gram-negative bacteria Chlamydia trachomatis and Neisseria gonorrhoeae are associated with an increased risk of HIV acquisition in South African women. HIV infection involves binding of the virus to CD4+ receptors on host cells and subsequent binding to ...

  3. The association of neoplasms and HIV infection in the correctional setting.

    Science.gov (United States)

    Baillargeon, Jacques; Pollock, Brad H; Leach, Charles T; Gao, Shou-Jiang

    2004-05-01

    HIV-associated immunosuppression has been linked to an increased risk of a number of cancers, including Kaposi sarcoma (KS), non-Hodgkin's lymphoma (NHL), and invasive cervical cancer. Because prison inmates constitute one of the highest HIV/AIDS prevalent populations in the US, understanding the link between HIV infection and cancer in the correctional setting holds particular public health relevance. The study population consisted of 336,668 Texas Department of Criminal Justice inmates who were incarcerated, for any duration, between 1 January 1999 and 31 December 2001. Inmates diagnosed with HIV infection exhibited elevated rates of KS, NHL, anal cancer, and Hodgkin's disease, after adjusting for age and race. The elevated rates of cancer among HIV-infected individuals, particularly prison inmates, may be mediated, in part, by high-risk behaviours. HIV-associated risk behaviours, including unsafe sexual practices, injection drug use, and prostitution may be associated with cancer-related risk behaviours, such as smoking, excessive alcohol consumption, and poor diet. It will be important for future investigators to examine the association between HIV infection and cancer risk with sufficiently large study cohorts and appropriate longitudinal designs.

  4. Human immunodeficiency virus-associated disruption of mucosal barriers and its role in HIV transmission and pathogenesis of HIV/AIDS disease

    Science.gov (United States)

    Tugizov, Sharof

    2016-01-01

    Abstract Oral, intestinal and genital mucosal epithelia have a barrier function to prevent paracellular penetration by viral, bacterial and other pathogens, including human immunodeficiency virus (HIV). HIV can overcome these barriers by disrupting the tight and adherens junctions of mucosal epithelia. HIV-associated disruption of epithelial junctions may also facilitate paracellular penetration and dissemination of other viral pathogens. This review focuses on possible molecular mechanisms of HIV-associated disruption of mucosal epithelial junctions and its role in HIV transmission and pathogenesis of HIV and acquired immune deficiency syndrome (AIDS). PMID:27583187

  5. Acceleration of Age-Associated Methylation Patterns in HIV-1-Infected Adults

    Science.gov (United States)

    Sehl, Mary; Sinsheimer, Janet S.; Hultin, Patricia M.; Hultin, Lance E.; Quach, Austin; Martínez-Maza, Otoniel; Horvath, Steve; Vilain, Eric; Jamieson, Beth D.

    2015-01-01

    Patients with treated HIV-1-infection experience earlier occurrence of aging-associated diseases, raising speculation that HIV-1-infection, or antiretroviral treatment, may accelerate aging. We recently described an age-related co-methylation module comprised of hundreds of CpGs; however, it is unknown whether aging and HIV-1-infection exert negative health effects through similar, or disparate, mechanisms. We investigated whether HIV-1-infection would induce age-associated methylation changes. We evaluated DNA methylation levels at >450,000 CpG sites in peripheral blood mononuclear cells (PBMC) of young (20-35) and older (36-56) adults in two separate groups of participants. Each age group for each data set consisted of 12 HIV-1-infected and 12 age-matched HIV-1-uninfected samples for a total of 96 samples. The effects of age and HIV-1 infection on methylation at each CpG revealed a strong correlation of 0.49, pmodules; module 3 (ME3) was significantly correlated with age (cor=0.70) and HIV-1 status (cor=0.31). Older HIV-1+ individuals had a greater number of hypermethylated CpGs across ME3 (p=0.015). In a multivariate model, ME3 was significantly associated with age and HIV status (Data set 1: βage= 0.007088, p=2.08 x 10-9; βHIV= 0.099574, p=0.0011; Data set 2: βage= 0.008762, p=1.27x 10-5; βHIV= 0.128649, p= 0.0001). Using this model, we estimate that HIV-1 infection accelerates age-related methylation by approximately 13.7 years in data set 1 and 14.7 years in data set 2. The genes related to CpGs in ME3 are enriched for polycomb group target genes known to be involved in cell renewal and aging. The overlap between ME3 and an aging methylation module found in solid tissues is also highly significant (Fisher-exact p=5.6 x 10-6, odds ratio=1.91). These data demonstrate that HIV-1 infection is associated with methylation patterns that are similar to age-associated patterns and suggest that general aging and HIV-1 related aging work through some common cellular

  6. Association of HIV prevalence and concurrency of sexual ...

    African Journals Online (AJOL)

    Association of HIV prevalence and concurrency of sexual partnerships in South Africa's language groups: An ecological analysis. C Kenyon. Abstract. Background. There is considerable variation in HIV prevalence between different language groups in South Africa (SA). Sexual partner concurrency has been linked to the ...

  7. Predictive Utility of Brief AUDIT for HIV Antiretroviral Medication Nonadherence

    Science.gov (United States)

    Broyles, Lauren Matukaitis; Gordon, Adam J.; Sereika, Susan M.; Ryan, Christopher M.; Erlen, Judith A.

    2012-01-01

    Alcohol use negatively affects adherence to antiretroviral therapy (ART), thus HIV/AIDS providers need accurate, efficient assessments of alcohol use. Using existing data from an efficacy trial of two cognitive-behavioral ART adherence interventions, we sought to determine if results on two common alcohol screening tests (Alcohol Use Disorders Identification Test—Consumption (AUDIT-C) and its binge-related question (AUDIT-3)) predict ART nonadherence. Twenty seven percent of the sample (n=308) were positive on the AUDIT-C and 34% were positive on the AUDIT-3. In multivariate analyses, AUDIT-C positive status predicted ART nonadherence after controlling for race, age, conscientiousness, and self-efficacy (p=.036). While AUDIT-3 positive status was associated with ART nonadherence in unadjusted analyses, this relationship was not maintained in the final multivariate model. The AUDIT-C shows potential as an indirect screening tool for both at-risk drinking and ART nonadherence, underscoring the relationship between alcohol and chronic disease management. PMID:22014256

  8. Factors Associated with HIV/AIDS in Sudan

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    Badreldin Abdelrhman Mohamed

    2013-01-01

    Full Text Available Objectives. To assess participants’ knowledge about HIV/AIDS and to identify the factors associated with HIV/AIDS in Sudan. Methods. Observational cross-sectional study carried out at Omdurman National Voluntary Counseling and Testing Centre, Sudan covered 870 participants. Sociodemographic data as well as information related to sexual behavior were collected. Results. Most of the respondents were knowledgeable about the true transmission modes for AIDS virus. Very few respondents knew someone infected with AIDS (4.5%, died of AIDS (8.1%, accepted to live with someone infected with AIDS (4.7% or to work with someone infected with AIDS (2.1%. Regarding sexual behavior, 96.5% had reported their first sexual experience between 20 and 30 years, with 85.7% reporting one or two partners, and only 1.8% reported using condom. Multivariate logistic regression showed that circumcision, religion, marital status, age at first sex, number of sexual partners, education level, and misconception of knowledge are the main risk factors associated with HIV/AIDS. Conclusion. Our results showed that a number of diversity risk factors were associated with HIV/AIDS. It is unlikely that a holistic approach will be found to immediately change sexual-risk-relating behavior. Interventions including sustained educational programs, promotion of condom, and encouragement of voluntary testing and active involvement of the country’s political and religious leaders will be needed to alleviate this problem.

  9. Characterization of LEDGF/p75 genetic variants and association with HIV-1 disease progression.

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    Peter Messiaen

    Full Text Available BACKGROUND: As Lens epithelium-derived growth factor (LEDGF/p75 is an important co-factor involved in HIV-1 integration, the LEDGF/p75-IN interaction is a promising target for the new class of allosteric HIV integrase inhibitors (LEDGINs. Few data are available on the genetic variability of LEDGF/p75 and the influence on HIV disease in vivo. This study evaluated the relation between LEDGF/p75 genetic variation, mRNA expression and HIV-1 disease progression in order to guide future clinical use of LEDGINs. METHODS: Samples were derived from a therapy-naïve cohort at Ghent University Hospital and a Spanish long-term-non-progressor cohort. High-resolution melting curve analysis and Sanger sequencing were used to identify all single nucleotide polymorphisms (SNPs in the coding region, flanking intronic regions and full 3'UTR of LEDGF/p75. In addition, two intronic tagSNPs were screened based on previous indication of influencing HIV disease. LEDGF/p75 mRNA was quantified in patient peripheral blood mononuclear cells (PBMC using RT-qPCR. RESULTS: 325 samples were investigated from patients of Caucasian (n = 291 and African (n = 34 origin, including Elite (n = 49 and Viremic controllers (n = 62. 21 SNPs were identified, comprising five in the coding region and 16 in the non-coding regions and 3'UTR. The variants in the coding region were infrequent and had no major impact on protein structure according to SIFT and PolyPhen score. One intronic SNP (rs2737828 was significantly under-represented in Caucasian patients (P<0.0001 compared to healthy controls (HapMap. Two SNPs showed a non-significant trend towards association with slower disease progression but not with LEDGF/p75 expression. The observed variation in LEDGF/p75 expression was not correlated with disease progression. CONCLUSIONS: LEDGF/p75 is a highly conserved protein. Two non-coding polymorphisms were identified indicating a correlation with disease outcome, but further

  10. Prolonged expression of an anti-HIV-1 gp120 minibody to the female rhesus macaque lower genital tract by AAV gene transfer.

    Science.gov (United States)

    Abdel-Motal, U M; Harbison, C; Han, T; Pudney, J; Anderson, D J; Zhu, Q; Westmoreland, S; Marasco, W A

    2014-09-01

    Topical microbicides are a leading strategy for prevention of HIV mucosal infection to women; however, numerous pharmacokinetic limitations associated with coitally related dosing strategy have contributed to their limited success. Here we test the hypothesis that adeno-associated virus (AAV) mediated delivery of the b12 human anti-HIV-1 gp120 minibody gene to the lower genital tract of female rhesus macaques (Rh) can provide prolonged expression of b12 minibodies in the cervical-vaginal secretions. Gene transfer studies demonstrated that, of various green fluorescent protein (GFP)-expressing AAV serotypes, AAV-6 most efficiently transduced freshly immortalized and primary genital epithelial cells (PGECs) of female Rh in vitro. In addition, AAV-6-b12 minibody transduction of Rh PGECs led to inhibition of SHIV162p4 transmigration and virus infectivity in vitro. AAV-6-GFP could also successfully transduce vaginal epithelial cells of Rh when applied intravaginally, including p63+ epithelial stem cells. Moreover, intravaginal application of AAV-6-b12 to female Rh resulted in prolonged minibody detection in their vaginal secretions throughout the 79-day study period. These data provide proof of principle that AAV-6-mediated delivery of anti-HIV broadly neutralizing antibody (BnAb) genes to the lower genital tract of female Rh results in persistent minibody detection for several months. This strategy offers promise that an anti-HIV-1 genetic microbicide strategy may be possible in which topical application of AAV vector, with periodic reapplication as needed, may provide sustained local BnAb expression and protection.

  11. Factors associated with HIV infection among delivered women in Sergipe, Brazil

    Directory of Open Access Journals (Sweden)

    Lemos Lígia

    2009-08-01

    Full Text Available Abstract Background In Brazil, the number of HIV cases has increased mostly amongst poor less educated women in the northeast region. This combination increased the risk for vertical transmission. This study aims to identify risk factors associated with HIV infection at delivery in Sergipe-NE Brazil. Findings This was a case-control study, with 39 cases and 117 controls that gave birth at the official health system hospitals. All patients were tested for HIV at hospital admission, using a rapid test and were interviewed about socioeconomic conditions and health attitudes and practices. Univariate and multivariate logistic analysis were performed to evaluate the factors associated with HIV infection. In the univariate analysis, association with HIV positivity was found for the variables "antenatal HIV test" (OR: 4.44; CI: 1.93 – 10.29 and "intravenous drug use" (OR = 12.08; 95% CI 1.28 – 8. Three patients were intravenous drug users, all HIV+. After logistic multivariate regression, not being tested for HIV during antenatal care (OR = 4.98; 95% CI: 2.13–12.22; p Conclusion Drug use, limited knowledge about how to prevent AIDS, and lack of HIV testing during pregnancy were risk factors for infection with HIV. Although it was not conceived to evaluate effectiveness of procedures to prevent vertical transmission, the risk factors here detected may corroborate official recommendation for rapid HIV testing at delivery as an effective procedure to prevent vertical transmission.

  12. Sexual behaviours, perception of risk of HIV infection, and factors associated with attending HIV post-test counselling in Ethiopia

    NARCIS (Netherlands)

    Sahlu, T.; Kassa, E.; Agonafer, T.; Tsegaye, A.; Rinke de Wit, T.; Gebremariam, H.; Doorly, R.; Spijkerman, I.; Yeneneh, H.; Coutinho, R. A.; Fontanet, A. L.

    1999-01-01

    OBJECTIVES: To describe sexual behaviours, perception of risk of HIV infection, and factors associated with attending HIV post-test counselling (PTC) among Ethiopian adults. METHODS: Data on socio-demographic characteristics, knowledge of HIV infection, sexual history, medical examination, and HIV

  13. Blood Gene Expression Predicts Bronchiolitis Obliterans Syndrome

    Directory of Open Access Journals (Sweden)

    Richard Danger

    2018-01-01

    Full Text Available Bronchiolitis obliterans syndrome (BOS, the main manifestation of chronic lung allograft dysfunction, leads to poor long-term survival after lung transplantation. Identifying predictors of BOS is essential to prevent the progression of dysfunction before irreversible damage occurs. By using a large set of 107 samples from lung recipients, we performed microarray gene expression profiling of whole blood to identify early biomarkers of BOS, including samples from 49 patients with stable function for at least 3 years, 32 samples collected at least 6 months before BOS diagnosis (prediction group, and 26 samples at or after BOS diagnosis (diagnosis group. An independent set from 25 lung recipients was used for validation by quantitative PCR (13 stables, 11 in the prediction group, and 8 in the diagnosis group. We identified 50 transcripts differentially expressed between stable and BOS recipients. Three genes, namely POU class 2 associating factor 1 (POU2AF1, T-cell leukemia/lymphoma protein 1A (TCL1A, and B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and 0.78 respectively. These genes allow stratification based on BOS risk (log-rank test p < 0.01 and are not associated with time posttransplantation. This is the first published large-scale gene expression analysis of blood after lung transplantation. The three-gene blood signature could provide clinicians with new tools to improve follow-up and adapt treatment of patients likely to develop BOS.

  14. Factors associated with linkage to HIV care and TB treatment at community-based HIV testing services in Cape Town, South Africa.

    Science.gov (United States)

    Meehan, Sue-Ann; Sloot, Rosa; Draper, Heather R; Naidoo, Pren; Burger, Ronelle; Beyers, Nulda

    2018-01-01

    Diagnosing HIV and/or TB is not sufficient; linkage to care and treatment is conditional to reduce the burden of disease. This study aimed to determine factors associated with linkage to HIV care and TB treatment at community-based services in Cape Town, South Africa. This retrospective cohort study utilized routinely collected data from clients who utilized stand-alone (fixed site not attached to a health facility) and mobile HIV testing services in eight communities in the City of Cape Town Metropolitan district, between January 2008 and June 2012. Clients were included in the analysis if they were ≥12 years and had a known HIV status. Generalized estimating equations (GEE) logistic regression models were used to assess the association between determinants (sex, age, HIV testing service and co-infection status) and self-reported linkage to HIV care and/or TB treatment. Linkage to HIV care was 3 738/5 929 (63.1%). Linkage to HIV care was associated with the type of HIV testing service. Clients diagnosed with HIV at mobile services had a significantly reduced odds of linking to HIV care (aOR 0.7 (CI 95%: 0.6-0.8), p<0.001. Linkage to TB treatment was 210/275 (76.4%). Linkage to TB treatment was not associated with sex and service type, but was associated with age. Clients in older age groups were less likely to link to TB treatment compared to clients in the age group 12-24 years (all, p-value<0.05). A large proportion of clients diagnosed with HIV at mobile services did not link to care. Almost a quarter of clients diagnosed with TB did not link to treatment. Integrated community-based HIV and TB testing services are efficient in diagnosing HIV and TB, but strategies to improve linkage to care are required to control these epidemics.

  15. Virtual Screening Models for Prediction of HIV-1 RT Associated RNase H Inhibition

    DEFF Research Database (Denmark)

    Poongavanam, Vasanthanathan; Kongsted, Jacob

    2013-01-01

    The increasing resistance to current therapeutic agents for HIV drug regiment remains a major problem for effective acquired immune deficiency syndrome (AIDS) therapy. Many potential inhibitors have today been developed which inhibits key cellular pathways in the HIV cycle. Inhibition of HIV-1...... databases. The methods used here include machine-learning algorithms (e.g. support vector machine, random forest and kappa nearest neighbor), shape similarity (rapid overlay of chemical structures), pharmacophore, molecular interaction fields-based fingerprints for ligands and protein (FLAP) and flexible...... for identifying structurally diverse and selective RNase H inhibitors from large chemical databases. In addition, pharmacophore models suggest that the inter-distance between hydrogen bond acceptors play a key role in inhibition of the RNase H domain through metal chelation....

  16. HIV-1 Tat reduces nephrin in human podocytes: a potential mechanism for enhanced glomerular permeability in HIV-associated nephropathy.

    Science.gov (United States)

    Doublier, Sophie; Zennaro, Cristina; Spatola, Tiziana; Lupia, Enrico; Bottelli, Antonella; Deregibus, Maria Chiara; Carraro, Michele; Conaldi, Pier Giulio; Camussi, Giovanni

    2007-02-19

    To determine whether HIV-1 Tat may directly alter glomerular permeability in HIV-associated nephropathy (HIVAN). Heavy proteinuria is a hallmark of HIVAN. The slit diaphragm is the ultimate glomerular filtration barrier critical for maintaining the efficiency of the ultrafiltration unit of the kidney. In this study, we evaluated the direct effect of Tat protein on the permeability of isolated glomeruli and on the expression of nephrin, the main slit diaphragm component, by human cultured podocytes. Permeability was studied by measuring the permeability to albumin in isolated rat glomeruli. We also evaluated the expression of nephrin in human cultured podocytes by using immunofluorescence and Western blot. We found that Tat increased albumin permeability in isolated glomeruli, and rapidly induced the redistribution and loss of nephrin in cultured podocytes. Pretreatment of glomeruli and podocytes with blocking antibodies showed that Tat reduced nephrin expression by engaging vascular endothelial growth factor receptors types 2 and 3 and the integrin alphavbeta3. Pre-incubation of podocytes with two platelet-activating factor (PAF) receptor antagonists prevented the loss and redistribution of nephrin induced by Tat, suggesting that PAF is an intracellular mediator of Tat action. Tat induced a rapid PAF synthesis by podocytes. When podocytes transfected to overexpress PAF-acetylhydrolase, the main catabolic enzyme of PAF, were stimulated with Tat, the redistribution and loss of nephrin was abrogated. The present results define a mechanism by which Tat may reduce nephrin expression in podocytes, thus increasing glomerular permeability. This provides new insights in the understanding of HIVAN pathogenesis.

  17. The mitochondrial translocator protein, TSPO, inhibits HIV-1 envelope glycoprotein biosynthesis via the endoplasmic reticulum-associated protein degradation pathway.

    Science.gov (United States)

    Zhou, Tao; Dang, Ying; Zheng, Yong-Hui

    2014-03-01

    The HIV-1 Env glycoprotein is folded in the endoplasmic reticulum (ER), which is necessary for viral entry and replication. Currently, it is still unclear how this process is regulated. The glycoprotein folding in the ER is controlled by the ER-associated protein degradation (ERAD) pathway, which specifically targets misfolded proteins for degradation. Previously, we reported that HIV-1 replication is restricted in the human CD4(+) T cell line CEM.NKR (NKR). To understand this mechanism, we first analyzed cellular protein expression in NKR cells and discovered that levels of the mitochondrial translocator protein TSPO were upregulated by ∼64-fold. Notably, when NKR cells were treated with TSPO antagonist PK-11195, Ro5-4864, or diazepam, HIV restriction was completely disrupted, and TSPO knockdown by short hairpin RNAs (shRNAs) achieved a similar effect. We next analyzed viral protein expression, and, interestingly, we discovered that Env expression was specifically inhibited. Both TSPO knockdown and treatment with TSPO antagonist could restore Env expression in NKR cells. We further discovered that Env proteins were rapidly degraded and that kifunensine, an ERAD pathway inhibitor, could restore Env expression and viral replication, indicating that Env proteins were misfolded and degraded through the ERAD pathway in NKR cells. We also knocked out the TSPO gene in 293T cells using CRISPR/Cas9 (clustered, regularly interspaced, short palindromic repeat [CRISPR]/CRISPR-associated-9) technology and found that TSPO could similarly inhibit Env expression in these cells. Taken together, these results demonstrate that TSPO inhibits Env protein expression through the ERAD pathway and suggest that mitochondria play an important role in regulating the Env folding process. The HIV-1 Env glycoprotein is absolutely required for viral infection, and an understanding of its expression pathway in infected cells will identify new targets for antiretroviral therapies. Env proteins

  18. Anxiety, depression, and HIV symptoms among persons living with HIV/AIDS: the role of hazardous drinking.

    Science.gov (United States)

    Garey, Lorra; Bakhshaie, Jafar; Sharp, Carla; Neighbors, Clayton; Zvolensky, Michael J; Gonzalez, Adam

    2015-01-01

    Hazardous drinking is common among persons living with HIV/AIDS (PLWHA) and associated with numerous negative health consequences. Despite the well-established negative effects of hazardous drinking among PLWHA, scholarly work has neglected to explore the role of such drinking in regard to anxiety/depressive symptoms and HIV symptom expression. The current study investigated associations between hazardous drinking and anxiety/depressive symptoms and HIV symptoms among PLWHA. Participants (n = 94; 88.3% male; Mage = 48.55; SD = 9.15) included PLWHA recruited from AIDS service organizations in the northeast. Hazardous drinking was significantly associated with anxiety/depressive symptoms and HIV symptom expression above and beyond the variance accounted for by sex, race, recruitment site, and CD4 T-Cell count, as well as other cognitive-affective variables (emotion dysregulation, distress intolerance, and anxiety sensitivity). The present results provide empirical support that hazardous drinking is indeed related to depressive and anxiety symptoms as well as HIV symptom distress and that this effect is not attributable to other factors commonly related to both alcohol use problems and emotional distress among PLWHA. Results highlight the importance of alcohol interventions for excessive drinking specifically tailored for PLWHA to facilitate better mental and physical health adjustment.

  19. Acceleration of age-associated methylation patterns in HIV-1-infected adults.

    Directory of Open Access Journals (Sweden)

    Tammy M Rickabaugh

    Full Text Available Patients with treated HIV-1-infection experience earlier occurrence of aging-associated diseases, raising speculation that HIV-1-infection, or antiretroviral treatment, may accelerate aging. We recently described an age-related co-methylation module comprised of hundreds of CpGs; however, it is unknown whether aging and HIV-1-infection exert negative health effects through similar, or disparate, mechanisms. We investigated whether HIV-1-infection would induce age-associated methylation changes. We evaluated DNA methylation levels at >450,000 CpG sites in peripheral blood mononuclear cells (PBMC of young (20-35 and older (36-56 adults in two separate groups of participants. Each age group for each data set consisted of 12 HIV-1-infected and 12 age-matched HIV-1-uninfected samples for a total of 96 samples. The effects of age and HIV-1 infection on methylation at each CpG revealed a strong correlation of 0.49, p<1 x 10(-200 and 0.47, p<1 x 10(-200. Weighted gene correlation network analysis (WGCNA identified 17 co-methylation modules; module 3 (ME3 was significantly correlated with age (cor=0.70 and HIV-1 status (cor=0.31. Older HIV-1+ individuals had a greater number of hypermethylated CpGs across ME3 (p=0.015. In a multivariate model, ME3 was significantly associated with age and HIV status (Data set 1: βage=0.007088, p=2.08 x 10(-9; βHIV=0.099574, p=0.0011; Data set 2: βage=0.008762, p=1.27 x 10(-5; βHIV=0.128649, p=0.0001. Using this model, we estimate that HIV-1 infection accelerates age-related methylation by approximately 13.7 years in data set 1 and 14.7 years in data set 2. The genes related to CpGs in ME3 are enriched for polycomb group target genes known to be involved in cell renewal and aging. The overlap between ME3 and an aging methylation module found in solid tissues is also highly significant (Fisher-exact p=5.6 x 10(-6, odds ratio=1.91. These data demonstrate that HIV-1 infection is associated with methylation patterns that

  20. Alcohol Enhances HIV Infection of Cord Blood Monocyte-Derived Macrophages

    Science.gov (United States)

    Mastrogiannis, Dimitrios S.; Wang, Xu; Dai, Min; Li, Jieliang; Wang, Yizhong; Zhou, Yu; Sakarcan, Selin; Peña, Juliet Crystal; Ho, Wenzhe

    2014-01-01

    Alcohol consumption or alcohol abuse is common among pregnant HIV+ women and has been identified as a potential behavioral risk factor for the transmission of HIV. In this study, we examined the impact of alcohol on HIV infection of cord blood monocyte-derived macrophages (CBMDM). We demonstrated that alcohol treatment of CBMDM significantly enhanced HIV infection of CBMDM. Investigation of the mechanisms of alcohol action on HIV demonstrated that alcohol inhibited the expression of several HIV restriction factors, including anti-HIV microRNAs, APOBEC3G and APOBEC3H. Additionally, alcohol also suppressed the expression of IFN regulatory factor 7 (IRF-7) and retinoic acid-inducible gene I (RIG-I), an intracellular sensor of viral infection. The suppression of these IFN regulatory factors was associated with reduced expression of type I IFN. These experimental findings suggest that maternal alcohol consumption may facilitate HIV infection, promoting vertical transmission of HIV. PMID:25053361

  1. Susceptibility to virus-cell fusion at the plasma membrane is reduced through expression of HIV gp41 cytoplasmic domains

    International Nuclear Information System (INIS)

    Malinowsky, Katharina; Luksza, Julia; Dittmar, Matthias T.

    2008-01-01

    The cytoplasmic tail of the HIV transmembrane protein plays an important role in viral infection. In this study we analyzed the role of retroviral cytoplasmic tails in modulating the cytoskeleton and interfering with virus-cell fusion. HeLaP4 cells expressing different HIV cytoplasmic tail constructs showed reduced acetylated tubulin levels whereas the cytoplasmic tail of MLV did not alter microtubule stability indicating a unique function for the lentiviral cytoplasmic tail. The effect on tubulin is mediated through the membrane proximal region of the HIV cytoplasmic tail and was independent of membrane localization. Site-directed mutagenesis identified three motifs in the HIV-2 cytoplasmic tail required to effect the reduction in acetylated tubulin. Both the YxxΦ domain and amino acids 21 to 45 of the HIV-2 cytoplasmic tail need to be present to change the level of acetylated tubulin in transfected cells. T-cells stably expressing one HIV-2 cytoplasmic tail derived construct showed also a reduction in acetylated tubulin thus confirming the importance of this effect not only for HeLaP4 and 293T cells. Challenge experiments using transiently transfected HeLaP4 cells and T cells stably expressing an HIV cytoplasmic tail construct revealed both reduced virus-cell fusion and replication of HIV-1 NL4.3 compared to control cells. In the virus-cell fusion assay only virions pseudotyped with either HIV or MLV envelopes showed reduced fusion efficiency, whereas VSV-G pseudotyped virions where not affected by the expression of HIV derived cytoplasmic tail constructs, indicating that fusion at the plasma but not endosomal membrane is affected. Overexpression of human histone-deacetylase 6 (HDAC6) and constitutively active RhoA resulted in a reduction of acetylated tubulin and reduced virus-cell fusion as significant as that observed following expression of HIV cytoplasmic tail constructs. Inhibition of HDAC6 showed a strong increase in acetylated tubulin and increase of

  2. Screening for human papillomavirus, cervical cytological abnormalities and associated risk factors in HIV-positive and HIV-negative women in Rwanda.

    Science.gov (United States)

    Mukanyangezi, M F; Sengpiel, V; Manzi, O; Tobin, G; Rulisa, S; Bienvenu, E; Giglio, D

    2018-02-01

    Cervical cancer is the major cause of death from cancer in Africa. We wanted to assess the prevalence of human papillomavirus (HPV) infections and associated risk factors and to determine whether HPV testing could serve as a screening method for squamous intraepithelial lesions (SILs) in Rwanda. We also wanted to obtain a broader understanding of the underlying risk factors for the establishment of HPV infection in Rwanda. A total of 206 HIV-positive women, 172 HIV-negative women and 22 women with unknown HIV status were recruited at the University Teaching Hospitals of Kigali (UTHK) and of Butare (UTHB) in Rwanda. Participants underwent an interview, cervical sampling for a Thinprep Pap test and a screening test analysing 37 HPV strains. Only 27% of HIV-positive women and 7% of HIV-negative women had been screened for cervical cancer before. HPV16 and HPV52 were the most common HPV strains. HIV-positive women were more commonly infected with high-risk (HR) HPV and multitype HPV than HIV-negative women. The sensitivity was 78% and the specificity 87% to detect high-grade SIL (HSIL) with HPV screening. Among HIV-negative women, being divorced was positively associated with HR-HPV infection, while hepatitis B, Trichomonas vaginalis infection and HR-HPV infection were factors positively associated with SILs. Ever having had gonorrhoea was positively associated with HR-HPV infection among HIV-positive women. HR-HPV infection and the number of live births were positively associated with SILs. The currently used quadrivalent vaccine may be insufficient to give satisfactory HPV coverage in Rwanda. HPV Screening may be effective to identify women at risk of developing cervical cancer, particularly if provided to high-risk patients. © 2017 British HIV Association.

  3. Bacterial vaginosis, alterations in vaginal flora and HIV genital shedding among HIV-1-infected women in Mozambique

    Directory of Open Access Journals (Sweden)

    Robert D Kirkcaldy

    2011-05-01

    Full Text Available Objectives. We investigated whether abnormal vaginal flora, including bacterial vaginosis (BV, are associated with detection of cervical HIV-1 RNA among HIV-infected women in Mozambique. Methods. We obtained clinical data and vaginal specimens from HIV-infected women registering for their first visit at one of two HIV care clinics in Mozambique. We compared women with detectable cervical HIV viral load (≥40 copies/ml with women with undetectable cervical HIV. Results. We enrolled 106 women. Women with abnormal vaginal flora (intermediate Nugent scores, 4 - 6 were more likely to have detectable cervical HIV RNA then women with normal vaginal flora (adjusted odds ratio 7.2 (95% confidence interval 1.8 - 29.1, adjusted for CD4 count. Women with BV had a non-significantly higher likelihood of detectable cervical HIV than women with normal flora. Conclusions. Abnormal vaginal flora were significantly associated with cervical HIV expression. Further research is needed to confirm this relationship.

  4. Ethanol concentration-dependent alterations in gene expression during acute binge drinking in the HIV-1 transgenic rat.

    Science.gov (United States)

    Sarkar, Sraboni; Chang, Sulie L

    2013-07-01

    Binge drinking of high ethanol (EtOH) concentration beverages is common among young adults and can be a risk factor for exposure to sexually transmitted diseases, including HIV-1. We used a novel noninfectious HIV-1 transgenic (HIV-1Tg) rat model that mimics HIV-1 patients in terms of altered immune responses and deficits in cognitive learning and memory to investigate EtOH concentration-dependent effects on 48 alcohol-modulated genes during binge EtOH administration. HIV-1Tg and control F344 rats were administered water, 8% EtOH, or 52% EtOH by gavage (i.g.) for 3 days (2.0 g/kg/d). Two hours after final treatment, blood, liver, and spleen were collected from each animal. Serum blood EtOH concentration (BEC) was measured, and gene expression in the liver and spleen was determined using a specifically designed PCR array. The BEC was significantly higher in the 52% EtOH-treated HIV-1Tg rats compared with the 8% EtOH group; however, the BEC was higher in the 8% EtOH-treated control rats compared with the 52% EtOH group. There was no change in expression of the EtOH metabolism-related genes, Adh1, Adh4, and Cyp2e1, in either the 8 or 52% EtOH-treated HIV-1Tg rats, whereas expression of those genes was significantly higher in the liver of the 52% EtOH control rats, but not in the 8% EtOH group. In the HIV-1Tg rats, expression of the GABAA , metabotropic glutamate, and dopamine neurotransmitter receptor genes was significantly increased in the spleen of the 52% EtOH group, but not in the 8% EtOH group, whereas no change was observed in those genes in either of the control groups. Our data indicate that, in the presence of HIV-1 infection, EtOH concentration-dependent binge drinking can have significantly different molecular effects. Copyright © 2013 by the Research Society on Alcoholism.

  5. Decreased chronic morbidity but elevated HIV associated cytokine levels in HIV-infected older adults receiving HIV treatment: benefit of enhanced access to care?

    Directory of Open Access Journals (Sweden)

    Portia C Mutevedzi

    Full Text Available The association of HIV with chronic morbidity and inflammatory markers (cytokines in older adults (50+years is potentially relevant for clinical care, but data from African populations is scarce.To examine levels of chronic morbidity by HIV and ART status in older adults (50+years and subsequent associations with selected pro-inflammatory cytokines and body mass index.Ordinary, ordered and generalized ordered logistic regression techniques were employed to compare chronic morbidity (heart disease (angina, arthritis, stroke, hypertension, asthma and diabetes and cytokines (Interleukins-1 and -6, C-Reactive Protein and Tumor Necrosis Factor-alpha by HIV and ART status on a cross-sectional random sample of 422 older adults nested within a defined rural South African population based demographic surveillance.Using a composite measure of all morbidities, controlling for age, gender, BMI, smoking and wealth quintile, HIV-infected individuals on ART had 51% decreased odds (95% CI:0.26-0.92 of current morbidity compared to HIV-uninfected. In adjusted regression, compared to HIV-uninfected, the proportional odds (aPOR of having elevated inflammation markers of IL6 (>1.56 pg/mL was nearly doubled in HIV-infected individuals on (aPOR 1.84; 95%CI: 1.05-3.21 and not on (aPOR 1.94; 95%CI: 1.11-3.41 ART. Compared to HIV-uninfected, HIV-infected individuals on ART had >twice partial proportional odds (apPOR=2.30;p=0.004 of having non-clinically significant raised hsCRP levels(>1 ug/mL; ART-naïve HIV-infected individuals had >double apPOR of having hsCRP levels indicative of increased heart disease risk(>3.9 ug/mL;p=0.008.Although HIV status was associated with increased inflammatory markers, our results highlight reduced morbidity in those receiving ART and underscore the need of pro-actively extending these services to HIV-uninfected older adults, beyond mere provision at fixed clinics. Providing health services through regular community chronic disease

  6. Pilot trial of an expressive writing intervention with HIV-positive methamphetamine-using men who have sex with men.

    Science.gov (United States)

    Carrico, Adam W; Nation, Austin; Gómez, Walter; Sundberg, Jeffrey; Dilworth, Samantha E; Johnson, Mallory O; Moskowitz, Judith T; Rose, Carol Dawson

    2015-06-01

    Among men who have sex with men (MSM), the co-occurrence of trauma and stimulant use has negative implications for HIV/AIDS prevention. HIV-positive, methamphetamine-using MSM were recruited to pilot test a 7-session, multicomponent resilient affective processing (RAP) intervention that included expressive writing exercises targeting HIV-related traumatic stress. An open-phase pilot with 10 participants provided support for feasibility of intervention delivery such that 99% of the RAP sessions were completed in a 1-month period. Subsequently, 23 additional participants were enrolled in a pilot randomized controlled trial of the RAP intervention (n = 12) versus an attention-control condition that included writing exercises about neutral topics (n = 11). Acceptability was evidenced by participants randomized to RAP expressing significantly more negative emotions in their writing and reporting greater likelihood of recommending expressive writing exercises to a friend living with HIV. Over the 3-month follow-up period, attention-control participants reported significant decreases in HIV-related traumatic stress while RAP intervention participants reported no significant changes. Compared to attention-control participants, those in the RAP intervention reported significant reductions in the frequency of methamphetamine use immediately following the 1-month RAP intervention period. Thematic analyses of RAP expressive writing exercises revealed that multiple negative life events characterized by social stigma or loss contribute to the complex nature of HIV-related traumatic stress. Findings support the feasibility and acceptability of an exposure-based intervention targeting HIV-related traumatic stress. However, more intensive intervention approaches that simultaneously target trauma and stimulant use will likely be needed to optimize HIV/AIDS prevention efforts with this population. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  7. HIV Risk Characteristics Associated with Violence Against Women: A Longitudinal Study Among Women in the United States.

    Science.gov (United States)

    Montgomery, Brooke E E; Frew, Paula M; Hughes, James P; Wang, Jing; Adimora, Adaora A; Haley, Danielle F; Kuo, Irene; Jennings, Larissa; El-Bassel, Nabila; Hodder, Sally L

    2018-06-15

    Using data from HIV Prevention Trials Network 064, a multisite, observational cohort study conducted to estimate HIV incidence rates among women living in areas of high poverty and HIV prevalence in the United States, we examined the use of HIV risk characteristics to predict emotional abuse, physical violence, and forced sex. Participants included 2099 women, 18-44 years of age, who reported unprotected vaginal or anal sex with a male partner and an additional personal or perceived male partner HIV risk characteristic in the past 6 months. Adjusting for time-varying covariates, generalized estimating equations were used to assess the ability of HIV risk characteristics to predict violence 6 months later. Reported analyses were limited to the 1980 study participants who reported having a male sex partner at that assessment. Exchanging sex, perceived partner concurrency, and perceived partner incarceration were significantly predictive of emotional abuse 6 months later (adjusted odds ratio [AOR]: 1.60; 1.59; 1.34, respectively). Prior sexually transmitted infection diagnosis, exchanging sex, and binge drinking were significantly predictive of physical violence 6 months later (AOR: 1.62; 1.71; 1.47, respectively). None of the variables measured was significantly predictive of forced sex. Strategies that address reducing violence against women should be studied further in the context of HIV prevention programs.

  8. Factors associated with D-dimer levels in HIV-infected individuals

    DEFF Research Database (Denmark)

    Borges, Alvaro H; O'Connor, Jemma L; Phillips, Andrew N

    2014-01-01

    BACKGROUND: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. METHODS: In this cross-sectional study, participants in three randomized controlled trials...... with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6...... viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high...

  9. Expression of Herpes Simplex Virus Thymidine Kinase/Ganciclovir by RNA Trans-Splicing Induces Selective Killing of HIV-Producing Cells

    Directory of Open Access Journals (Sweden)

    Carin K. Ingemarsdotter

    2017-06-01

    Full Text Available Antiviral strategies targeting hijacked cellular processes are less easily evaded by the virus than viral targets. If selective for viral functions, they can have a high therapeutic index. We used RNA trans-splicing to deliver the herpes simplex virus thymidine kinase-ganciclovir (HSV-tk/GCV cell suicide system into HIV-producing cells. Using an extensive in silico bioinformatics and RNA structural analysis approach, ten HIV RNA trans-splicing constructs were designed targeting eight different HIV splice donor or acceptor sites and were tested in cells expressing HIV. Trans-spliced mRNAs were identified in HIV-expressing cells using qRT-PCR with successful detection of fusion RNA transcripts between HIV RNA and the HSV-tk RNA transcripts from six of ten candidate RNA trans-splicing constructs. Conventional PCR and Sanger sequencing confirmed RNA trans-splicing junctions. Measuring cell viability in the presence or absence of GCV expression of HSV-tk by RNA trans-splicing led to selective killing of HIV-producing cells using either 3′ exon replacement or 5′ exon replacement in the presence of GCV. Five constructs targeting four HIV splice donor and acceptor sites, D4, A5, A7, and A8, involved in regulating the generation of multiple HIV RNA transcripts proved to be effective for trans-splicing mediated selective killing of HIV-infected cells, within which individual constructs targeting D4 and A8 were the most efficient.

  10. Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans.

    Science.gov (United States)

    Gottlieb, Assaf; Daneshjou, Roxana; DeGorter, Marianne; Bourgeois, Stephane; Svensson, Peter J; Wadelius, Mia; Deloukas, Panos; Montgomery, Stephen B; Altman, Russ B

    2017-11-24

    Genome-wide association studies are useful for discovering genotype-phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into "gene level" effects. Previous work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression-on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals. We build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations. Our results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at https://github.com/assafgo/warfarin-cohort.

  11. Oxidative Stress Predicts All-Cause Mortality in HIV-Infected Patients.

    Directory of Open Access Journals (Sweden)

    Mar Masiá

    Full Text Available We aimed to assess whether oxidative stress is a predictor of mortality in HIV-infected patients.We conducted a nested case-control study in CoRIS, a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Cases were patients who died with available stored plasma samples collected. Two age and sex-matched controls for each case were selected. We measured F2-isoprostanes (F2-IsoPs and malondialdehyde (MDA plasma levels in the first blood sample obtained after cohort engagement.54 cases and 93 controls were included. Median F2-IsoPs and MDA levels were significantly higher in cases than in controls. When adjustment was performed for age, HIV-transmission category, CD4 cell count and HIV viral load at cohort entry, and subclinical inflammation measured with highly-sensitive C-reactive protein (hsCRP, the association of F2-IsoPs with mortality remained significant (adjusted OR per 1 log10 increase, 2.34 [1.23-4.47], P = 0.009. The association of MDA with mortality was attenuated after adjustment: adjusted OR (95% CI per 1 log10 increase, 2.05 [0.91-4.59], P = 0.080. Median hsCRP was also higher in cases, and it also proved to be an independent predictor of mortality in the adjusted analysis: OR (95% CI per 1 log10 increase, 1.39 (1.01-1.91, P = 0.043; and OR (95% CI per 1 log10 increase, 1.46 (1.07-1.99, P = 0.014, respectively, when adjustment included F2-IsoPs and MDA.Oxidative stress is a predictor of all-cause mortality in HIV-infected patients. For plasma F2-IsoPs, this association is independent of HIV-related factors and subclinical inflammation.

  12. Simplifying consent for HIV testing is associated with an increase in HIV testing and case detection in highest risk groups, San Francisco January 2003-June 2007.

    Directory of Open Access Journals (Sweden)

    Nicola M Zetola

    2008-07-01

    Full Text Available Populations at highest risk for HIV infection face multiple barriers to HIV testing. To facilitate HIV testing procedures, the San Francisco General Hospital Medical Center eliminated required written patient consent for HIV testing in its medical settings in May 2006. To describe the change in HIV testing rates in different hospital settings and populations after the change in HIV testing policy in the SFDH medical center, we performed an observational study using interrupted time series analysis.Data from all patients aged 18 years and older seen from January 2003 through June 2007 at the San Francisco Department of Public Health (SFDPH medical care system were included in the analysis. The monthly HIV testing rate per 1000 had patient-visits was calculated for the overall population and stratified by hospital setting, age, sex, race/ethnicity, homelessness status, insurance status and primary language.By June 2007, the average monthly rate of HIV tests per 1000 patient-visits increased 4.38 (CI, 2.17-6.60, p<0.001 over the number predicted if the policy change had not occurred (representing a 44% increase. The monthly average number of new positive HIV tests increased from 8.9 (CI, 6.3-11.5 to 14.9 (CI, 10.6-19.2, p<0.001, representing a 67% increase. Although increases in HIV testing were seen in all populations, populations at highest risk for HIV infection, particularly men, the homeless, and the uninsured experienced the highest increases in monthly HIV testing rates after the policy change.The elimination of the requirement for written consent in May 2006 was associated with a significant and sustained increase in HIV testing rates and HIV case detection in the SFDPH medical center. Populations facing the higher barriers to HIV testing had the highest increases in HIV testing rates and case detection in response to the policy change.

  13. Methamphetamine inhibits HIV-1 replication in CD4+ T cells by modulating anti-HIV-1 miRNA expression.

    Science.gov (United States)

    Mantri, Chinmay K; Mantri, Jyoti V; Pandhare, Jui; Dash, Chandravanu

    2014-01-01

    Methamphetamine is the second most frequently used illicit drug in the United States. Methamphetamine abuse is associated with increased risk of HIV-1 acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. Although a direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be established in patients, methamphetamine has been shown to increase HIV-1 replication in macrophages, dendritic cells, and cells of HIV transgenic mice. Intriguingly, the effects of methamphetamine on HIV-1 replication in human CD4(+) T cells that serve as the primary targets of infection in vivo are not clearly understood. Therefore, we examined HIV-1 replication in primary CD4(+) T cells in the presence of methamphetamine in a dose-dependent manner. Our results demonstrate that methamphetamine had a minimal effect on HIV-1 replication at concentrations of 1 to 50 μmol/L. However, at concentrations >100 μmol/L, it inhibited HIV-1 replication in a dose-dependent manner. We also discovered that methamphetamine up-regulated the cellular anti-HIV-1 microRNAs (miR-125b, miR-150, and miR-28-5p) in CD4(+) T cells. Knockdown experiments illustrated that up-regulation of the anti-HIV miRNAs inhibited HIV-1 replication. These results are contrary to the paradigm that methamphetamine accentuates HIV-1 pathogenesis by increasing HIV-1 replication. Therefore, our findings underline the complex interaction between drug use and HIV-1 and necessitate comprehensive understanding of the effects of methamphetamine on HIV-1 pathogenesis. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. Factors Associated with Delayed Enrollment in HIV Medical Care among HIV-Positive Individuals in Odessa Region, Ukraine.

    Science.gov (United States)

    Neduzhko, Oleksandr; Postnov, Oleksandr; Perehinets, Ihor; DeHovitz, Jack; Joseph, Michael; Odegaard, David; Kaplan, Robert; Kiriazova, Tetiana

    In Ukraine, about one-third of identified HIV-positive individuals are not connected to care. We conducted a cross-sectional survey (n = 200) among patients registered at Odessa AIDS centers in October to December 2011. Factors associated with delayed enrollment in HIV care (>3 months since positive HIV test) were evaluated using logistic regression. Among study participants (mean age 35 ± 8.2 years, 47.5% female, 42.5% reported history of injecting drugs), 55% delayed HIV care enrollment. Odds of delayed enrollment were higher for those with lower educational attainment (adjusted odds ratio [aOR]: 2.65, 95% confidence interval [CI]: 1.04-6.76), not feeling ill (aOR: 2.98, 95% CI: 1.50-5.93), or not having time to go to the AIDS center (aOR: 3.89, 95% CI: 1.39-10.89); injection drug use was not associated with delayed enrollment. Programs linking HIV-positive individuals to specialized care should address enrollment barriers and include education on HIV care benefits and case management for direct linkage to care. HIV testing and treatment should be coupled to ensure a continuum of care.

  15. Stigma in Ethiopia: association with depressive symptoms in people with HIV.

    Science.gov (United States)

    Endeshaw, Meheret; Walson, Judd; Rawlins, Sarah; Dessie, Abere; Alemu, Shitaye; Andrews, Nancy; Rao, Deepa

    2014-01-01

    Rates of depression among people living with HIV can be as high as 50%. In many settings, HIV-related stigma has been associated with depressive symptoms which may lead to poor engagement in care and ultimately, poorer health outcomes. Stigma is a major issue in Ethiopia but data examining the relationship between stigma and depression in Ethiopia are lacking. We performed a mixed-methods cross-sectional study to examine the relationship between stigma of HIV/AIDS and depressive symptoms in Gondar, Ethiopia. We interviewed patients who presented for routine HIV care at Gondar University Hospital during the study period, examining depressive symptoms and HIV/AIDS-related stigma using standardized measures. Multiple-regression was used to assess the relationship between depressive symptoms, stigma, and gender. Of 55 patients included in this analysis, 63.6% were female and most participants had limited formal education (69%, less than 12th grade education). The majority reported experiencing both stigma (78%) and depressive symptoms (60%) ranging in severity from mild to moderately severe. Higher levels of HIV-related stigma were significantly associated with higher levels of depressive symptoms (β = 0.464, p ≤ 0.001). Although gender was associated with stigma, it was not associated with depressive symptoms (β = -0.027, p > 0.05). Results suggest the importance of psychosocial issues in the lives of people with HIV in Ethiopia.

  16. The Cervicovaginal Microbiota and Its Associations With Human Papillomavirus Detection in HIV-Infected and HIV-Uninfected Women.

    Science.gov (United States)

    Reimers, Laura L; Mehta, Supriya D; Massad, L Stewart; Burk, Robert D; Xie, Xianhong; Ravel, Jacques; Cohen, Mardge H; Palefsky, Joel M; Weber, Kathleen M; Xue, Xiaonan; Anastos, Kathryn; Minkoff, Howard; Atrio, Jessica; D'Souza, Gypsyamber; Ye, Qian; Colie, Christine; Zolnik, Christine P; Spear, Gregory T; Strickler, Howard D

    2016-11-01

     Bacterial vaginosis (BV) is characterized by low abundance of Lactobacillus species, high pH, and immune cell infiltration and has been associated with an increased risk of human papillomavirus (HPV) infection. We molecularly assessed the cervicovaginal microbiota over time in human immunodeficiency virus (HIV)-infected and HIV-uninfected women to more comprehensively study the HPV-microbiota relationship, controlling for immune status.  16S ribosomal RNA gene amplicon pyrosequencing and HPV DNA testing were conducted annually in serial cervicovaginal lavage specimens obtained over 8-10 years from African American women from Chicago, of whom 22 were HIV uninfected, 22 were HIV infected with a stable CD4 + T-cell count of > 500 cells/mm 3 , and 20 were HIV infected with progressive immunosuppression. Vaginal pH was serially measured.  The relative abundances of Lactobacillus crispatus and other Lactobacillus species were inversely associated with vaginal pH (all P < .001). High (vs low) L. crispatus relative abundance was associated with decreased HPV detection (odds ratio, 0.48; 95% confidence interval, .24-.96; P trend = .03) after adjustment for repeated observation and multiple covariates, including pH and study group. However, there were no associations between HPV and the relative abundance of Lactobacillus species as a group, nor with Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii individually.  L. crispatus may have a beneficial effect on the burden of HPV in both HIV-infected and HIV-uninfected women (independent of pH). © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  17. To be or not to be sick and tired: Managing the visibility of HIV and HIV-related fatigue.

    Science.gov (United States)

    Schuft, Laura; Duval, Estelle; Thomas, Julie; Ferez, Sylvain

    2017-01-01

    This article takes a new direction in exploring HIV-related fatigue by adopting a qualitative interactionist approach. We analyse the social meanings attributed to fatigue among people living with HIV in France, the social gains and losses of its visibility and the social frames that condition its discursive and physical expression. The two-part methodology combines grounded theory analysis of 50 transcribed unstructured interviews conducted across France and participant observations within four HIV-related associations. Results reveal that the visibility of fatigue is in part dependent on the visibility of this stigmatized illness. The expression of fatigue is therefore closely linked with disclosure and concerns about HIV stigma. The degree to which HIV and HIV-related fatigue are rendered (in)visible also depends on structural factors including gender prescriptions, as well as context effects such as the type of social or 'care' relations involved in the social frame of interaction.

  18. An updated prediction model of the global risk of cardiovascular disease in HIV-positive persons

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Ryom, Lene; Smith, Colette

    2016-01-01

    ,663 HIV-positive persons from 20 countries in Europe and Australia, who were free of CVD at entry into the Data-collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study. Cox regression models (full and reduced) were developed that predict the risk of a global CVD endpoint. The predictive performance...... significantly predicted risk more accurately than the recalibrated Framingham model (Harrell's c-statistic of 0.791, 0.783 and 0.766 for the D:A:D full, D:A:D reduced, and Framingham models respectively; p models also more accurately predicted five-year CVD-risk for key prognostic subgroups...... to quantify risk and to guide preventive care....

  19. Viral-Associated GN: Hepatitis C and HIV.

    Science.gov (United States)

    Kupin, Warren L

    2017-08-07

    Viruses are capable of inducing a wide spectrum of glomerular disorders that can be categorized on the basis of the duration of active viremia: acute, subacute, or chronic. The variable responses of the adaptive immune system to each time period of viral infection results mechanistically in different histologic forms of glomerular injury. The unique presence of a chronic viremic carrier state with either hepatitis C (HCV) or HIV has led to the opportunity to study in detail various pathogenic mechanisms of viral-induced glomerular injury, including direct viral infection of renal tissue and the development of circulating immune complexes composed of viral antigens that deposit along the glomerular basement membrane. Epidemiologic data show that approximately 25%-30% of all HIV patients are coinfected with HCV and 5%-10% of all HCV patients are coinfected with HIV. This situation can often lead to a challenging differential diagnosis when glomerular disease occurs in this dual-infected population and requires the clinician to be familiar with the clinical presentation, laboratory workup, and pathophysiology behind the development of renal disease for both HCV and HIV. Both of these viruses can be categorized under the new classification of infection-associated GN as opposed to being listed as causes of postinfectious GN as has previously been applied to them. Neither of these viruses lead to renal injury after a latent period of controlled and inactive viremia. The geneses of HCV- and HIV-associated glomerular diseases share a total dependence on the presence of active viral replication to sustain renal injury so the renal disease cannot be listed under "postinfectious" GN. With the new availability of direct-acting antivirals for HCV and more effective combined antiretroviral therapy for HIV, successful remission and even regression of glomerular lesions can be achieved if initiated at an early stage. Copyright © 2017 by the American Society of Nephrology.

  20. Factors Associated with HIV Prevalence and HIV Testing in Sierra Leone: Findings from the 2008 Demographic Health Survey.

    Directory of Open Access Journals (Sweden)

    Nataliya Brima

    Full Text Available The Sierra Leone Demographic Health Survey 2008 found an HIV prevalence of 1.5%. This study investigates associations with HIV infection and HIV testing.Households were selected using stratified multi-stage sampling. In all selected households women aged 15-49 were eligible. In every second household men aged 15-59 were also eligible. Participants were asked to consent for anonymous HIV testing. All participants interviewed and tested were analysed. Multiple logistic regression identified associations with HIV infection, undiagnosed infection and with ever having a voluntary HIV test among sexually active participants.Of 7495 invited 86% (6,475 agreed to an interview and HIV test. Among 96 HIV positive participants, 78% had never taken a voluntary HIV test so were unaware of their serostatus, and 86% were sexually active in the last 12 months among whom 96% did not use a condom at last intercourse. 11% of all participants had previously voluntarily tested. Among women who had tested, 60% did so in antenatal care. We found that those living in an urban area, and those previously married, were more likely to be HIV infected. Voluntary HIV testing was more common in those aged 25-44, living in an urban area, females, having secondary or higher education, having first sexual intercourse at age 17 years or older, and using condoms at last sex. Although 82% of men and 69% of women had heard of HIV, only 35% and 29% respectively had heard of antiretroviral therapy.The HIV prevalence in Sierra Leone has been stable. HIV testing, however, is uncommon and most infected individuals are unaware of their serostatus. This could allow the epidemic to escalate as individuals with undiagnosed infection are unlikely to change their behaviour or access treatment. Improving knowledge and increasing testing need to remain central to HIV prevention interventions in Sierra Leone.

  1. Fluctuations in Blood Marginal Zone B-Cell Frequencies May Reflect Migratory Patterns Associated with HIV-1 Disease Progression Status.

    Science.gov (United States)

    Gauvin, Julie; Chagnon-Choquet, Josiane; Poudrier, Johanne; Roger, Michel

    2016-01-01

    We have previously shown that overexpression of BLyS/BAFF was associated with increased relative frequencies of innate "precursor" marginal zone (MZ)-like B-cells in the blood of HIV-1-infected rapid and classic progressors. However, along with relatively normal BLyS/BAFF expression levels, these cells remain unaltered in elite-controllers (EC), rather, percentages of more mature MZ-like B-cells are decreased in the blood of these individuals. Fluctuations in frequencies of blood MZ-like B-cell populations may reflect migratory patterns associated with disease progression status, suggesting an important role for these cells in HIV-1 pathogenesis. We have therefore longitudinally measured plasma levels of B-tropic chemokines by ELISA-based technology as well as their ligands by flow-cytometry on blood B-cell populations of HIV-1-infected individuals with different rates of disease progression and uninfected controls. Migration potential of B-cell populations from these individuals were determined by chemotaxis assays. We found important modulations of CXCL13-CXCR5, CXCL12-CXCR4/CXCR7, CCL20-CCR6 and CCL25-CCR9 chemokine-axes and increased cell migration patterns in HIV progressors. Interestingly, frequencies of CCR6 expressing cells were significantly elevated within the precursor MZ-like population, consistent with increased migration in response to CCL20. Although we found little modulation of chemokine-axes in EC, cell migration was greater than that observed for uninfected controls, especially for MZ-like B-cells. Overall the immune response against HIV-1 may involve recruitment of MZ-like B-cells to peripheral sites. Moreover, our findings suggest that "regulated" attraction of these cells in a preserved BLyS/BAFF non-inflammatory environment, such as encountered in EC could be beneficial to the battle and even control of HIV.

  2. High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

    Science.gov (United States)

    Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

    2017-06-01

    Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  3. The association of psychiatric disorders and HIV infection in the correctional setting.

    Science.gov (United States)

    Baillargeon, Jacques; Ducate, Suzanne; Pulvino, John; Bradshaw, Patrick; Murray, Owen; Olvera, Rene

    2003-10-01

    Psychiatric disorders, such as bipolar disorder, schizophrenia, and depression, have been associated with both HIV-associated risk behaviors and HIV infection. While the US prison population is reported to exhibit elevated rates of HIV/AIDS and most psychiatric disorders, scarce information currently exists on the association of these conditions in the prison setting. The present study examined the association of six major psychiatric disorders with HIV infection in one of the nation's largest prison populations. The study population consisted of 336,668 Texas Department of Criminal Justice inmates who were incarcerated for any duration between January 1, 1999 and December 31, 2001. Information on medical conditions and sociodemographic factors was obtained from an institution-wide medical information system. Inmates diagnosed with HIV infection exhibited elevated rates of major depression, dysthymia, bipolar disorder, schizophrenia, schizoaffective disorder, and non-schizophrenic psychotic disorder. These rates persisted in stratified analyses and in a multivariate analysis that statistically adjusted for gender, race, and age category. The present cross-sectional study's finding of a positive association between HIV infection and psychiatric diagnoses among inmates holds both clinical and public health relevance. It will be important for future investigations to prospectively assess the underlying mechanisms of these associations in the correctional setting.

  4. HIV-1 Infection Is Associated with Depletion and Functional Impairment of Mycobacterium tuberculosis-Specific CD4 T Cells in Individuals with Latent Tuberculosis Infection.

    Science.gov (United States)

    Day, Cheryl L; Abrahams, Deborah A; Harris, Levelle D; van Rooyen, Michele; Stone, Lynnett; de Kock, Marwou; Hanekom, Willem A

    2017-09-15

    Coinfection with HIV is the single greatest risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis disease. HIV-associated dysregulation of adaptive immunity by depletion of CD4 Th cells most likely contributes to loss of immune control of LTBI in HIV-infected individuals, although the precise mechanisms whereby HIV infection impedes successful T cell-mediated control of M. tuberculosis have not been well defined. To further delineate mechanisms whereby HIV impairs protective immunity to M. tuberculosis , we evaluated the frequency, phenotype, and functional capacity of M. tuberculosis -specific CD4 T cells in HIV-infected and HIV-uninfected adults with LTBI. HIV infection was associated with a lower total frequency of cytokine-producing M. tuberculosis -specific CD4 T cells, and preferential depletion of a discrete subset of M. tuberculosis -specific IFN-γ + IL-2 - TNF-α + CD4 T cells. M. tuberculosis -specific CD4 T cells in HIV-infected individuals expressed significantly higher levels of Ki67, compared with HIV-uninfected individuals, thus indicating recent activation and turnover of these cells in vivo. The ex vivo proliferative capacity of M. tuberculosis -specific CD4 T cells was markedly impaired in HIV-infected individuals, compared with HIV-uninfected individuals. Moreover, HIV infection was associated with increased M. tuberculosis Ag-induced CD4 T cell death ex vivo, indicating a possible mechanism contributing to impaired proliferative capacity of M. tuberculosis -specific CD4 T cells in HIV-infected individuals. These data provide new insights into the parameters of M. tuberculosis -specific CD4 T cell immunity that are impaired in HIV-infected individuals with LTBI, which may contribute to their increased risk of developing active tuberculosis disease. Copyright © 2017 by The American Association of Immunologists, Inc.

  5. CD147 expression predicts biochemical recurrence after prostatectomy independent of histologic and pathologic features.

    Science.gov (United States)

    Bauman, Tyler M; Ewald, Jonathan A; Huang, Wei; Ricke, William A

    2015-07-25

    CD147 is an MMP-inducing protein often implicated in cancer progression. The purpose of this study was to investigate the expression of CD147 in prostate cancer (PCa) progression and the prognostic ability of CD147 in predicting biochemical recurrence after prostatectomy. Plasma membrane-localized CD147 protein expression was quantified in patient samples using immunohistochemistry and multispectral imaging, and expression was compared to clinico-pathological features (pathologic stage, Gleason score, tumor volume, preoperative PSA, lymph node status, surgical margins, biochemical recurrence status). CD147 specificity and expression were confirmed with immunoblotting of prostate cell lines, and CD147 mRNA expression was evaluated in public expression microarray datasets of patient prostate tumors. Expression of CD147 protein was significantly decreased in localized tumors (pT2; p = 0.02) and aggressive PCa (≥pT3; p = 0.004), and metastases (p = 0.001) compared to benign prostatic tissue. Decreased CD147 was associated with advanced pathologic stage (p = 0.009) and high Gleason score (p = 0.02), and low CD147 expression predicted biochemical recurrence (HR 0.55; 95 % CI 0.31-0.97; p = 0.04) independent of clinico-pathologic features. Immunoblot bands were detected at 44 kDa and 66 kDa, representing non-glycosylated and glycosylated forms of CD147 protein, and CD147 expression was lower in tumorigenic T10 cells than non-tumorigenic BPH-1 cells (p = 0.02). Decreased CD147 mRNA expression was associated with increased Gleason score and pathologic stage in patient tumors but is not associated with recurrence status. Membrane-associated CD147 expression is significantly decreased in PCa compared to non-malignant prostate tissue and is associated with tumor progression, and low CD147 expression predicts biochemical recurrence after prostatectomy independent of pathologic stage, Gleason score, lymph node status, surgical margins, and tumor volume in multivariable

  6. Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters.

    Directory of Open Access Journals (Sweden)

    Oliver F Brandenberg

    2017-05-01

    Full Text Available The potential of broadly neutralizing antibodies targeting the HIV-1 envelope trimer to prevent HIV-1 transmission has opened new avenues for therapies and vaccines. However, their implementation remains challenging and would profit from a deepened mechanistic understanding of HIV-antibody interactions and the mucosal transmission process. In this study we experimentally determined stoichiometric parameters of the HIV-1 trimer-antibody interaction, confirming that binding of one antibody is sufficient for trimer neutralization. This defines numerical requirements for HIV-1 virion neutralization and thereby enables mathematical modelling of in vitro and in vivo antibody neutralization efficacy. The model we developed accurately predicts antibody efficacy in animal passive immunization studies and provides estimates for protective mucosal antibody concentrations. Furthermore, we derive estimates of the probability for a single virion to start host infection and the risks of male-to-female HIV-1 transmission per sexual intercourse. Our work thereby delivers comprehensive quantitative insights into both the molecular principles governing HIV-antibody interactions and the initial steps of mucosal HIV-1 transmission. These insights, alongside the underlying, adaptable modelling framework presented here, will be valuable for supporting in silico pre-trial planning and post-hoc evaluation of HIV-1 vaccination or antibody treatment trials.

  7. Triterpenoids from Ocimum labiatum Activates Latent HIV-1 Expression In Vitro: Potential for Use in Adjuvant Therapy

    Directory of Open Access Journals (Sweden)

    Petrina Kapewangolo

    2017-10-01

    Full Text Available Latent HIV reservoirs in infected individuals prevent current treatment from eradicating infection. Treatment strategies against latency involve adjuvants for viral reactivation which exposes viral particles to antiretroviral drugs. In this study, the effect of novel triterpenoids isolated from Ocimum labiatum on HIV-1 expression was measured through HIV-1 p24 antigen capture in the U1 latency model of HIV-1 infection and in peripheral blood mononuclear cells (PBMCs of infected patients on combination antiretroviral therapy (cART. The mechanism of viral reactivation was determined through the compound’s effect on cytokine production, histone deacetylase (HDAC inhibition, and protein kinase C (PKC activation. Cytotoxicity of the triterpenoids was determined using a tetrazolium dye and flow cytometry. The isolated triterpene isomers, 3-hydroxy-4,6a,6b,11,12,14b-hexamethyl-1,2,3,4,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-octadecahydropicene-4,8a-dicarboxylic acid (HHODC, significantly (p < 0.05 induced HIV-1 expression in a dose-dependent manner in U1 cells at non-cytotoxic concentrations. HHODC also induced viral expression in PBMCs of HIV-1 infected patients on cART. In addition, the compound up-regulated the production of interleukin (IL-2, IL-6, tumour necrosis factor (TNF-α, and interferon (IFN-γ but had no effect on HDAC and PKC activity, suggesting cytokine upregulation as being involved in latency activation. The observed in vitro reactivation of HIV-1 introduces the adjuvant potential of HHODC for the first time here.

  8. Metabolic complications associated with HIV protease inhibitor therapy.

    Science.gov (United States)

    Nolan, David

    2003-01-01

    HIV protease inhibitors were introduced into clinical practice over 7 years ago as an important component of combination antiretroviral drug regimens which in many ways revolutionised the treatment of HIV infection. The significant improvements in prognosis that have resulted from the use of these regimens, combined with the need for lifelong treatment, have increasingly focused attention on the adverse effects of antiretroviral drugs and on the metabolic complications of HIV protease inhibitors in particular. In this review, the cluster of metabolic abnormalities characterised by triglyceride-rich dyslipidaemia and insulin resistance associated with HIV protease inhibitor therapy are considered, along with implications for cardiovascular risk in patients affected by these complications. Toxicity profiles of individual drugs within the HIV protease inhibitor class are examined, as there is an increased recognition of significant intra-class differences both in terms of absolute risk of metabolic complications as well as the particular metabolic phenotype associated with these drugs. Guidelines for clinical assessment and treatment are emphasised, along with pathophysiological mechanisms that may provide a rational basis for the treatment of metabolic complications. Finally, these drug-specific effects are considered within the context of HIV-specific effects on lipid metabolism as well as lifestyle factors that have contributed to a rapidly increasing incidence of similar metabolic syndromes in the general population. These data highlight the importance of individualising patient management in terms of choice of antiretroviral regimen, assessment of metabolic outcomes and use of therapeutic interventions, based on the assessment of baseline (pre-treatment) metabolic status as well as the presence of potentially modifiable cardiovascular risk factors.

  9. HIV Status Discordance: Associated Factors Among HIV Positive ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    infection for a partner of a person with HIV is about 10%, with higher annual transmission rates ... We recommend the tracking of both men and women as index cases in other to reduce HIV .... HIV status was accepted as known only if backed.

  10. Perceived HIV-associated stigma among HIV-seropositive men: psychometric study of HIV stigma scale

    Directory of Open Access Journals (Sweden)

    Adrian eValle

    2015-07-01

    Full Text Available Objectives: To assess the internal consistency and factor structure of the abridged Spanish version of the Berger HIV Stigma Scale (HSS-21, provide evidence for its convergent and discriminant validity, and describe perceived stigma in an urban population from northeast Mexico. Methods: Seventy five HIV-positive men who have sex with men (MSM were recruited. Participants answered the Spanish versions of three Likert-type scales: HSS-21, Robsenberg’s self-esteem scale, and the abbreviated version of the Zung’s Depression Scale.Results: HSS-21 showed high reliability and validity; its factor structure included four components: concern with public attitudes; negative self-image; disclosure concerns; and enacted stigma. The level of stigma was high in 27 out of 75 (36% participants; nevertheless, the score found in the component related to disclosure concerns indicated high level of stigma in 68% of participants. The score of HSS-21 was positively correlated with the score of depression and negatively correlated with the score of self-esteem. Conclusion: Results demonstrated high reliability for the HSS-21; correlations with other scales supported its validity. This scale demonstrated to be a practical tool for assessing stigma among Mexican HIV-positive MSM. High level of stigma was found only in the factor related to disclosure concerns. Policy Implications: Identifying HIV-associated stigma through a short, reliable and validated instrument will allow the development of interventions that cope and manage stigma in HIV-positive MSM. HSS-21 distinguishes between different dimensions of stigma and will contribute to a better understanding of this phenomenon.

  11. Nef enhances HIV-1 infectivity via association with the virus assembly complex

    International Nuclear Information System (INIS)

    Qi Mingli; Aiken, Christopher

    2008-01-01

    The HIV-1 accessory protein Nef enhances virus infectivity by facilitating an early post-entry step of infection. Nef acts in the virus producer cell, leading to a beneficial modification to HIV-1 particles. Nef itself is incorporated into HIV-1 particles, where it is cleaved by the viral protease during virion maturation. To probe the role of virion-associated Nef in HIV-1 infection, we generated a fusion protein consisting of the host protein cyclophilin A (CypA) linked to the amino terminus of Nef. The resulting CypA-Nef protein enhanced the infectivity of Nef-defective HIV-1 particles and was specifically incorporated into the virions via association with Gag during particle assembly. Pharmacologic or genetic inhibition of CypA-Nef binding to Gag prevented incorporation of CypA-Nef into virions and inhibited infectivity enhancement. Our results indicate that infectivity enhancement by Nef requires its association with a component of the assembling HIV-1 particle

  12. Modeling HIV-associated neurocognitive disorders in mice: new approaches in the changing face of HIV neuropathogenesis

    OpenAIRE

    Laura B. Jaeger; Avindra Nath

    2012-01-01

    It is well established that infection with the human immunodeficiency virus (HIV) leads to immune suppression. Less well known is the fact that long-term, progressive HIV disease is associated with the development of cognitive deficits. Since the introduction of combined antiretroviral therapy (cART), the clinical presentation of HIV infection has evolved into a chronic illness with very low levels of viral replication and chronic immune activation, with compliant affected individuals survivi...

  13. HIV/AIDS Related Knowledge and Perceived Risk Associated with ...

    African Journals Online (AJOL)

    Using data from the 2004 National Survey of Adolescents in Uganda, logistic regression models were fitted to examine the odds that HIV/AIDS related knowledge and perceived risk of HIV infection are associated with condom use among adolescents. After including demographic measures, findings indicated that correct ...

  14. HIV-1 Tat depresses DNA-PKCS expression and DNA repair, and sensitizes cells to ionizing radiation

    International Nuclear Information System (INIS)

    Sun Yi; Huang Yuechen; Xu Qinzhi; Wang Huiping; Bai Bei; Sui Jianli; Zhou Pingkun

    2006-01-01

    Purpose There is accumulating evidence that cancer patients with human immmunodeficiency virus-1/acquired immunodeficency syndrome (HIV-1/AIDS) have more severe tissue reactions and often develop cutaneous toxic effects when subjected to radiotherapy. Here we explored the effects of the HIV-1 Tat protein on cellular responses to ionizing radiation. Methods and Materials Two Tat-expressing cell lines, TT2 and TE671-Tat, were derived from human rhabdomyosarcoma cells by transfecting with the HIV-1 tat gene. Radiosensitivity was determined using colony-forming ability. Gene expression was assessed by cDNA microarray and immunohybridization. The Comet assay and γ-H2AX foci were use to detect DNA double-strand breaks (DSBs) and repair. Radiation-induced cell cycle changes were detected by flow cytometry. Results The radiosensitivity of TT2 and TE671-Tat cells was significantly increased as compared with parental TE671 cells or the control TE671-pCI cells. Tat also increased proliferation activity. The comet assay and γH2AX foci detection revealed a decreased capacity to repair radiation-induced DNA DSBs in Tat-expressing cells. Microarray assay demonstrated that the DNA repair gene DNA-PKcs, and cell cycle-related genes Cdc20, Cdc25C, KIF2C and CTS1 were downregulated in Tat-expressing cells. Depression of DNA-PKcs in Tat-expressing cells was further confirmed by RT-PCR and immuno-hybridization analysis. Tat-expressing cells exhibited a prolonged S phase arrest after 4 Gy γ-irradiation, and a noticeable delay in the initiation and elimination of radiation-induced G 2 /M arrest as compared with parental cells. In addition, the G 2 /M arrest was incomplete in TT2 cells. Moreover, HIV-1 Tat resulted in a constitutive overexpression of cyclin B1 protein. Conclusion HIV-1 Tat protein sensitizes cells to ionizing radiation via depressing DNA repair and dysregulating cell cycle checkpoints. These observations provide new insight into the increased tissue reactions of AIDS

  15. The CD8⁺ memory stem T cell (T(SCM)) subset is associated with improved prognosis in chronic HIV-1 infection.

    Science.gov (United States)

    Ribeiro, Susan P; Milush, Jeffrey M; Cunha-Neto, Edecio; Kallas, Esper G; Kalil, Jorge; Somsouk, Ma; Hunt, Peter W; Deeks, Steven G; Nixon, Douglas F; SenGupta, Devi

    2014-12-01

    Memory stem T cells (T(SCM)) constitute a long-lived, self-renewing lymphocyte population essential for the maintenance of functional immunity. The hallmarks of HIV-1 pathogenesis are CD4(+) T cell depletion and abnormal cellular activation. We investigated the impact of HIV-1 infection on the T(SCM) compartment, as well as any protective role these cells may have in disease progression, by characterizing this subset in a cohort of 113 subjects with various degrees of viral control on and off highly active antiretroviral therapy (HAART). We observed that the frequency of CD8(+) T(SCM) was decreased in all individuals with chronic, untreated HIV-1 infection and that HAART had a restorative effect on this subset. In contrast, natural controllers of HIV-1 had the highest absolute number of CD4(+) T(SCM) cells among all of the infected groups. The frequency of CD4(+) T(SCM) predicted higher CD8(+) T(SCM) frequencies, consistent with a role for the CD4(+) subset in helping to maintain CD8(+) memory T cells. In addition, T(SCM) appeared to be progenitors for effector T cells (TEM), as these two compartments were inversely correlated. Increased frequencies of CD8(+) T(SCM) predicted lower viral loads, higher CD4(+) counts, and less CD8(+) T cell activation. Finally, we found that T(SCM) express the mucosal homing integrin α4β7 and can be identified in gut-associated lymphoid tissue (GALT). The frequency of mucosal CD4(+) T(SCM) was inversely correlated with that in the blood, potentially reflecting the ability of these self-renewing cells to migrate to a crucial site of ongoing viral replication and CD4(+) T cell depletion. HIV-1 infection leads to profound impairment of the immune system. T(SCM) constitute a recently identified lymphocyte subset with stem cell-like qualities, including the ability to generate other memory T cell subtypes, and are therefore likely to play an important role in controlling viral infection. We investigated the relationship between the size

  16. Proteomic Profiling of a Primary CD4+ T Cell Model of HIV-1 Latency Identifies Proteins Whose Differential Expression Correlates with Reactivation of Latent HIV-1.

    Science.gov (United States)

    Saha, Jamaluddin Md; Liu, Hongbing; Hu, Pei-Wen; Nikolai, Bryan C; Wu, Hulin; Miao, Hongyu; Rice, Andrew P

    2018-01-01

    The latent HIV-1 reservoir of memory CD4 + T cells that persists during combination antiviral therapy prevents a cure of infection. Insight into mechanisms of latency and viral reactivation are essential for the rational design of strategies to reduce the latent reservoir. In this study, we quantified the levels of >2,600 proteins in the CCL19 primary CD4 + T cell model of HIV-1 latency. We profiled proteins under conditions that promote latent infection and after cells were treated with phorbol 12-myristate 13-acetate (PMA) + ionomycin, which is known to efficiently induce reactivation of latent HIV-1. In an analysis of cells from two healthy blood donors, we identified 61 proteins that were upregulated ≥2-fold, and 36 proteins that were downregulated ≥2-fold under conditions in which latent viruses were reactivated. These differentially expressed proteins are, therefore, candidates for cellular factors that regulate latency or viral reactivation. Two unexpected findings were obtained from the proteomic data: (1) the interactions among the majority of upregulated proteins are largely undetermined in published protein-protein interaction networks and (2) downregulated proteins are strongly associated with Gene Ontology terms related to mitochondrial protein synthesis. This proteomic data set provides a useful resource for future mechanistic studies of HIV-1 latency.

  17. MicroRNAs upregulated during HIV infection target peroxisome biogenesis factors: Implications for virus biology, disease mechanisms and neuropathology.

    Directory of Open Access Journals (Sweden)

    Zaikun Xu

    2017-06-01

    Full Text Available HIV-associated neurocognitive disorders (HAND represent a spectrum neurological syndrome that affects up to 25% of patients with HIV/AIDS. Multiple pathogenic mechanisms contribute to the development of HAND symptoms including chronic neuroinflammation and neurodegeneration. Among the factors linked to development of HAND is altered expression of host cell microRNAs (miRNAs in brain. Here, we examined brain miRNA profiles among HIV/AIDS patients with and without HAND. Our analyses revealed differential expression of 17 miRNAs in brain tissue from HAND patients. A subset of the upregulated miRNAs (miR-500a-5p, miR-34c-3p, miR-93-3p and miR-381-3p, are predicted to target peroxisome biogenesis factors (PEX2, PEX7, PEX11B and PEX13. Expression of these miRNAs in transfected cells significantly decreased levels of peroxisomal proteins and concomitantly decreased peroxisome numbers or affected their morphology. The levels of miR-500a-5p, miR-34c-3p, miR-93-3p and miR-381-3p were not only elevated in the brains of HAND patients, but were also upregulated during HIV infection of primary macrophages. Moreover, concomitant loss of peroxisomal proteins was observed in HIV-infected macrophages as well as in brain tissue from HIV-infected patients. HIV-induced loss of peroxisomes was abrogated by blocking the functions of the upregulated miRNAs. Overall, these findings point to previously unrecognized miRNA expression patterns in the brains of HIV patients. Targeting peroxisomes by up-regulating miRNAs that repress peroxisome biogenesis factors may represent a novel mechanism by which HIV-1 subverts innate immune responses and/or causes neurocognitive dysfunction.

  18. Neoplasms HIV associated Kaposi sarcoma not

    International Nuclear Information System (INIS)

    Lombardo, K.; Sosa, A.; Krygier, G.; Muse, I.

    2004-01-01

    Abstract - The incidence of malignancies in virus carriers acquired immunodeficiency (HIV) has increased in conjunction with the disease during the past decade. 40% of all AIDS patients develop cancer during the course of HIV infection. Kaposi's sarcoma (KS), Non-Hodgkin lymphoma (NHL) and cervical cancer have an impact extremely high in HIV infected patients, and they are considered as disease AIDS-defining stage. Many reports suggest that other neoplasms they can have a high impact on the population of HIV carrier, including head and neck carcinoma, rectal cancer - anal, plasma cytomas, and melanoma lung cancer. Methods - We examined the spectrum of cancer in HIV-infected patients, specifically neoplasms except Kaposi sarcoma diagnosed between 1/1998 - 6/2004. Information on age, sex, factors was gathered risk for AIDS, neoplasms and mortality rate. Results: The total number of patients in our study was 21 patients, what 15 were male (71%) and 6 females (29%); the median age was 36 (29-70). Tumors were reported: 11 Non-Hodgkin lymphomas (52%), 2 Hodgkin's lymphoma (6.6%), 1 medullary thyroid cancer (6.6%), 1 melanoma (6.6%), 1 rectal cancer (5%) and three head and neck cancers (14%), 1 cancer 1 lung and breast cancer. Five of the patients were intravenous drug abusers (24%); 4 patients were homosexual, bisexual March 8 straight, on 6 patients know the data. Conclusions - The spectrum of malignancies associated with infection HIV in our study was similar to that described in other populations. ratio between the immune system and the epidemiology of the virus-induced tumors is to importance to identify new therapeutic approaches in the treatment and / or prevention of these neoplasms

  19. Improved therapy-success prediction with GSS estimated from clinical HIV-1 sequences.

    Science.gov (United States)

    Pironti, Alejandro; Pfeifer, Nico; Kaiser, Rolf; Walter, Hauke; Lengauer, Thomas

    2014-01-01

    Rules-based HIV-1 drug-resistance interpretation (DRI) systems disregard many amino-acid positions of the drug's target protein. The aims of this study are (1) the development of a drug-resistance interpretation system that is based on HIV-1 sequences from clinical practice rather than hard-to-get phenotypes, and (2) the assessment of the benefit of taking all available amino-acid positions into account for DRI. A dataset containing 34,934 therapy-naïve and 30,520 drug-exposed HIV-1 pol sequences with treatment history was extracted from the EuResist database and the Los Alamos National Laboratory database. 2,550 therapy-change-episode baseline sequences (TCEB) were assigned to test set A. Test set B contains 1,084 TCEB from the HIVdb TCE repository. Sequences from patients absent in the test sets were used to train three linear support vector machines to produce scores that predict drug exposure pertaining to each of 20 antiretrovirals: the first one uses the full amino-acid sequences (DEfull), the second one only considers IAS drug-resistance positions (DEonlyIAS), and the third one disregards IAS drug-resistance positions (DEnoIAS). For performance comparison, test sets A and B were evaluated with DEfull, DEnoIAS, DEonlyIAS, geno2pheno[resistance], HIVdb, ANRS, HIV-GRADE, and REGA. Clinically-validated cut-offs were used to convert the continuous output of the first four methods into susceptible-intermediate-resistant (SIR) predictions. With each method, a genetic susceptibility score (GSS) was calculated for each therapy episode in each test set by converting the SIR prediction for its compounds to integer: S=2, I=1, and R=0. The GSS were used to predict therapy success as defined by the EuResist standard datum definition. Statistical significance was assessed using a Wilcoxon signed-rank test. A comparison of the therapy-success prediction performances among the different interpretation systems for test set A can be found in Table 1, while those for test set

  20. Serodiagnostic profiles of HIV and HIV pathogenesis in vivo

    NARCIS (Netherlands)

    Goudsmit, J.; Lange, J. M.; Smit, L.; Bakker, M.; Klaver, B.; Danner, S. A.; Coutinho, R. A.

    1988-01-01

    Different stages of HIV infection are marked by expression of HIV genes, production of HIV antibodies, formation of antigen/antibody complexes and clearance of such complexes. Transient HIV antigenemia appearing generally 6-8 weeks prior to HIV antibody (HIV-Ab) seroconversion and lasting 3-4 months

  1. Future-oriented tweets predict lower county-level HIV prevalence in the United States.

    Science.gov (United States)

    Ireland, Molly E; Schwartz, H Andrew; Chen, Qijia; Ungar, Lyle H; Albarracín, Dolores

    2015-12-01

    Future orientation promotes health and well-being at the individual level. Computerized text analysis of a dataset encompassing billions of words used across the United States on Twitter tested whether community-level rates of future-oriented messages correlated with lower human immunodeficiency virus (HIV) rates and moderated the association between behavioral risk indicators and HIV. Over 150 million tweets mapped to U.S. counties were analyzed using 2 methods of text analysis. First, county-level HIV rates (cases per 100,000) were regressed on aggregate usage of future-oriented language (e.g., will, gonna). A second data-driven method regressed HIV rates on individual words and phrases. Results showed that counties with higher rates of future tense on Twitter had fewer HIV cases, independent of strong structural predictors of HIV such as population density. Future-oriented messages also appeared to buffer health risk: Sexually transmitted infection rates and references to risky behavior on Twitter were associated with higher HIV prevalence in all counties except those with high rates of future orientation. Data-driven analyses likewise showed that words and phrases referencing the future (e.g., tomorrow, would be) correlated with lower HIV prevalence. Integrating big data approaches to text analysis and epidemiology with psychological theory may provide an inexpensive, real-time method of anticipating outbreaks of HIV and etiologically similar diseases. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  2. Nuclear trafficking of the HIV-1 pre-integration complex depends on the ADAM10 intracellular domain

    International Nuclear Information System (INIS)

    Endsley, Mark A.; Somasunderam, Anoma D.; Li, Guangyu; Oezguen, Numan; Thiviyanathan, Varatharasa; Murray, James L.; Rubin, Donald H.; Hodge, Thomas W.

    2014-01-01

    Previously, we showed that ADAM10 is necessary for HIV-1 replication in primary human macrophages and immortalized cell lines. Silencing ADAM10 expression interrupted the HIV-1 life cycle prior to nuclear translocation of viral cDNA. Furthermore, our data indicated that HIV-1 replication depends on the expression of ADAM15 and γ-secretase, which proteolytically processes ADAM10. Silencing ADAM15 or γ-secretase expression inhibits HIV-1 replication between reverse transcription and nuclear entry. Here, we show that ADAM10 expression also supports replication in CD4 + T lymphocytes. The intracellular domain (ICD) of ADAM10 associates with the HIV-1 pre-integration complex (PIC) in the cytoplasm and immunoprecipitates and co-localizes with HIV-1 integrase, a key component of PIC. Taken together, our data support a model whereby ADAM15/γ-secretase processing of ADAM10 releases the ICD, which then incorporates into HIV-1 PIC to facilitate nuclear trafficking. Thus, these studies suggest ADAM10 as a novel therapeutic target for inhibiting HIV-1 prior to nuclear entry. - Highlights: • Nuclear trafficking of the HIV-1 pre-integration complex depends on ADAM10. • ADAM10 associates with HIV-1 integrase in the pre-integration complex. • HIV-1 replication depends on the expression of ADAM15 and γ-secretase. • Silencing ADAM15 or γ-secretase expression inhibits nuclear import of viral cDNA. • ADAM10 is important for HIV-1 replication in human macrophages and CD4 + T lymphocytes

  3. Nuclear trafficking of the HIV-1 pre-integration complex depends on the ADAM10 intracellular domain

    Energy Technology Data Exchange (ETDEWEB)

    Endsley, Mark A., E-mail: maendsle@utmb.edu [Department Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 (United States); Somasunderam, Anoma D., E-mail: asomasun@utmb.edu [Department Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 (United States); Li, Guangyu, E-mail: LIG001@mail.etsu.edu [Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 (United States); Oezguen, Numan, E-mail: numan.oezguen@bcm.edu [Department of Pathology and Immunology, Microbiome Center, Texas Children' s Hospital, Houston, TX 77030 (United States); Thiviyanathan, Varatharasa, E-mail: Varatharasa.Thiviyanathan@uth.tmc.edu [Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030 (United States); Murray, James L., E-mail: jmurray100@yahoo.com [GeneTAG Technology, Inc., 3155 Northwoods Place, Norcross, GA 30071 (United States); Rubin, Donald H., E-mail: don.h.rubin@vanderbilt.edu [Research Medicine, VA Tennessee Valley Healthcare System, 1310 24th Ave. South, Nashville, TN 37212 (United States); Departments of Medicine, Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, 1161 21st Ave South, Nashville, TN 37232 (United States); Hodge, Thomas W., E-mail: twhodge3@gmail.com [Pre-clinical and Antiviral Research, Tamir Biotechnology, Inc., 12625 High Bluff Dr., Suite 113, San Diego, CA 92130 (United States); and others

    2014-04-15

    Previously, we showed that ADAM10 is necessary for HIV-1 replication in primary human macrophages and immortalized cell lines. Silencing ADAM10 expression interrupted the HIV-1 life cycle prior to nuclear translocation of viral cDNA. Furthermore, our data indicated that HIV-1 replication depends on the expression of ADAM15 and γ-secretase, which proteolytically processes ADAM10. Silencing ADAM15 or γ-secretase expression inhibits HIV-1 replication between reverse transcription and nuclear entry. Here, we show that ADAM10 expression also supports replication in CD4{sup +} T lymphocytes. The intracellular domain (ICD) of ADAM10 associates with the HIV-1 pre-integration complex (PIC) in the cytoplasm and immunoprecipitates and co-localizes with HIV-1 integrase, a key component of PIC. Taken together, our data support a model whereby ADAM15/γ-secretase processing of ADAM10 releases the ICD, which then incorporates into HIV-1 PIC to facilitate nuclear trafficking. Thus, these studies suggest ADAM10 as a novel therapeutic target for inhibiting HIV-1 prior to nuclear entry. - Highlights: • Nuclear trafficking of the HIV-1 pre-integration complex depends on ADAM10. • ADAM10 associates with HIV-1 integrase in the pre-integration complex. • HIV-1 replication depends on the expression of ADAM15 and γ-secretase. • Silencing ADAM15 or γ-secretase expression inhibits nuclear import of viral cDNA. • ADAM10 is important for HIV-1 replication in human macrophages and CD4{sup +} T lymphocytes.

  4. Prediction of HIV-1 sensitivity to broadly neutralizing antibodies shows a trend towards resistance over time.

    Science.gov (United States)

    Hake, Anna; Pfeifer, Nico

    2017-10-01

    Treatment with broadly neutralizing antibodies (bNAbs) has proven effective against HIV-1 infections in humanized mice, non-human primates, and humans. Due to the high mutation rate of HIV-1, resistance testing of the patient's viral strains to the bNAbs is still inevitable. So far, bNAb resistance can only be tested in expensive and time-consuming neutralization experiments. Here, we introduce well-performing computational models that predict the neutralization response of HIV-1 to bNAbs given only the envelope sequence of the virus. Using non-linear support vector machines based on a string kernel, the models learnt even the important binding sites of bNAbs with more complex epitopes, i.e., the CD4 binding site targeting bNAbs, proving thereby the biological relevance of the models. To increase the interpretability of the models, we additionally provide a new kind of motif logo for each query sequence, visualizing those residues of the test sequence that influenced the prediction outcome the most. Moreover, we predicted the neutralization sensitivity of around 34,000 HIV-1 samples from different time points to a broad range of bNAbs, enabling the first analysis of HIV resistance to bNAbs on a global scale. The analysis showed for many of the bNAbs a trend towards antibody resistance over time, which had previously only been discovered for a small non-representative subset of the global HIV-1 population.

  5. Epidemiology of respiratory syncytial virus-associated acute lower respiratory tract infection hospitalizations among HIV-infected and HIV-uninfected South African children, 2010-2011.

    Science.gov (United States)

    Moyes, Jocelyn; Cohen, Cheryl; Pretorius, Marthi; Groome, Michelle; von Gottberg, Anne; Wolter, Nicole; Walaza, Sibongile; Haffejee, Sumayya; Chhagan, Meera; Naby, Fathima; Cohen, Adam L; Tempia, Stefano; Kahn, Kathleen; Dawood, Halima; Venter, Marietjie; Madhi, Shabir A

    2013-12-15

    There are limited data on respiratory syncytial virus (RSV) infection among children in settings with a high prevalence of human immunodeficiency virus (HIV). We studied the epidemiology of RSV-associated acute lower respiratory tract infection (ALRTI) hospitalizations among HIV-infected and HIV-uninfected children in South Africa. Children aged infection among HIV-infected and uninfected children were examined. The relative risk of hospitalization in HIV-infected and HIV-uninfected children was calculated in 1 site with population denominators. Of 4489 participants, 4293 (96%) were tested for RSV, of whom 1157 (27%) tested positive. With adjustment for age, HIV-infected children had a 3-5-fold increased risk of hospitalization with RSV-associated ALRTI (2010 relative risk, 5.6; [95% confidence interval (CI), 4.5-6.4]; 2011 relative risk, 3.1 [95% CI, 2.6-3.6]). On multivariable analysis, HIV-infected children with RSV-associated ALRTI had higher odds of death (adjusted odds ratio. 31.1; 95% CI, 5.4-179.8) and hospitalization for >5 days (adjusted odds ratio, 4.0; 95% CI, 1.5-10.6) than HIV-uninfected children. HIV-infected children have a higher risk of hospitalization with RSV-associated ALRTI and a poorer outcome than HIV-uninfected children. These children should be targeted for interventions aimed at preventing severe RSV disease.

  6. A stably expressed llama single-domain intrabody targeting Rev displays broad-spectrum anti-HIV activity.

    Science.gov (United States)

    Boons, Eline; Li, Guangdi; Vanstreels, Els; Vercruysse, Thomas; Pannecouque, Christophe; Vandamme, Anne-Mieke; Daelemans, Dirk

    2014-12-01

    The HIV Rev protein mediates the transport of partially and unspliced HIV mRNA from the nucleus to the cytoplasm. Rev multimerizes on a secondary stem-loop structure present in the viral intron-containing mRNA species and recruits the cellular karyopherin CRM1 to export viral mRNAs from the nucleus to the cytoplasm. Previously we have identified a single-domain intrabody (Nb(190)), derived from a llama heavy-chain antibody, which efficiently inhibits Rev multimerization and suppresses the production of infectious virus. We recently mapped the epitope of this nanobody and demonstrated that Rev residues K20 and Y23 are crucial for interaction while residues V16, H53 and L60 are important to a lesser extent. Here, we generated cell lines stably expressing Nb(190) and assessed the capacity of these cell lines to suppress the replication of different HIV-1 subtypes. These cells stably expressing the single-domain antibody are protected from virus-induced cytopathogenic effect even in the context of high multiplicity of infection. In addition, the replication of different subtypes of group M and one strain of group O is significantly suppressed in these cell lines. Next, we analysed the natural variations of Rev amino acids in sequence samples from HIV-1 infected patients worldwide and assessed the effect of Nb(190) on the most prevalent polymorphisms occurring at the key epitope positions (K20 and Y23) in Rev. We found that Nb(190) was able to suppress the function of these Rev variants except for the K20N mutant, which was present in only 0.7% of HIV-1 sequence populations (n = 4632). Cells stably expressing the single-domain intrabody Nb(190) are protected against virus-induced cytopathogenic effect and display a selective survival advantage upon infection. In addition, Nb(190) suppresses the replication of a wide range of different HIV-1 subtypes. Large-scale sequence analysis reveals that the Nb(190) epitope positions in Rev are well conserved across major HIV-1

  7. Knowledge and Concern about STIs/HIV and Sociodemographic Variables Associated with Getting Tested for HIV Among the General Population in Spain.

    Science.gov (United States)

    Teva, Inmaculada; de Araújo, Ludgleydson Fernandes; de la Paz Bermúdez, María

    2018-07-04

    HIV testing is important in terms of prevention and treatment. However, HIV testing rates in the Spanish general population remains low. Therefore, HIV testing promotion constitutes a key issue. A high level of knowledge about HIV/AIDS is associated with having been tested for HIV. The general aim of this study was to determine the prevalence of people who had ever been tested for HIV in Spain. The sample consisted of 1,106 participants from the general population - 60.0% females and 40.0% males - aged between 17 and 55 years old. The assessment instruments were a questionnaire on sociodemographic data and HIV testing, a scale of knowledge about STIs and HIV/AIDS, and a scale of concern about STIs/HIV. Results showed that greater knowledge about STIs and HIV was associated with a greater likelihood of being tested for HIV (OR = .77; 95.0% CI = .73-.82; p concern about HIV/AIDS decreased the likelihood of not having been tested for HIV (OR = .87; 95.0% CI = .83-.92; p concern about STIs was, the lower their likelihood of not having been tested for HIV was (OR = .87; 95.0% CI = .83-.91; p < .05). It is necessary to promote HIV testing in the general population as well as to consider their socio-demographic and psychological characteristics.

  8. Expression of HIV-1 antigens in plants as potential subunit vaccines

    CSIR Research Space (South Africa)

    Meyers, A

    2008-06-23

    Full Text Available Open AcceResearch article Expression of HIV-1 antigens in plants as potential subunit vaccines Ann Meyers1,2, Ereck Chakauya1,2,3, Enid Shephard1,4, Fiona L Tanzer1,2, James Maclean1,2, Alisson Lynch1,2, Anna-Lise Williamson1,5 and Edward P Rybicki...Figure 1 The HIV-1 Gag-derived proteins used in this study. Scale diagram showing (A) native Pr55Gag ORF organisation in the Page 2 of 15 (page number not for citation purposes) gag gene, (B) the p17/p24 fusion protein ORF, (C) p24 ORF. ORFs labelled p7...

  9. μ-opioid modulation of HIV-1 coreceptor expressionand HIV-1 replication

    International Nuclear Information System (INIS)

    Steele, Amber D.; Henderson, Earl E.; Rogers, Thomas J.

    2003-01-01

    A substantial proportion of HIV-1-infected individuals are intravenous drug users (IVDUs) who abuse opiates. Opioids induce a number of immunomodulatory effects that may directly influence HIV-1 disease progression. In the present report, we have investigated the effect of opioids on the expression of the major HIV-1 coreceptors CXCR4 and CCR5. For these studies we have focused on opiates which are ligands for the μ-opioid receptor. Our results show that DAMGO, a selective μ-opioid agonist, increases CXCR4 and CCR5 expression in both CD3 + lymphoblasts and CD14 + monocytes three- to fivefold. Furthermore, DAMGO-induced elevation of HIV-1 coreceptor expression translates into enhanced replication of both X4 and R5 viral strains of HIV-1. We have confirmed the role of the μ-opioid receptor based on the ability of a μ-opioid receptor-selective antagonist to block the effects of DAMGO. We have also found that morphine enhances CXCR4 and CCR5 expression and subsequently increases both X4 and R5 HIV-1 infection. We suggest that the capacity of μ-opioids to increase HIV-1 coreceptor expression and replication may promote viral binding, trafficking of HIV-1-infected cells, and enhanced disease progression

  10. Expression of Human CD4 and chemokine receptors in cotton rat cells confers permissiveness for productive HIV infection

    Directory of Open Access Journals (Sweden)

    Broder Christopher C

    2009-05-01

    Full Text Available Abstract Background Current small animal models for studying HIV-1 infection are very limited, and this continues to be a major obstacle for studying HIV-1 infection and pathogenesis, as well as for the urgent development and evaluation of effective anti-HIV-1 therapies and vaccines. Previously, it was shown that HIV-1 can infect cotton rats as indicated by development of antibodies against all major proteins of the virus, the detection of viral cDNA in spleen and brain of challenged animals, the transmission of infectious virus, albeit with low efficiency, from animal to animal by blood, and an additional increase in the mortality in the infected groups. Results Using in vitro experiments, we now show that cotton rat cell lines engineered to express human receptor complexes for HIV-1 (hCD4 along with hCXCR4 or hCCR5 support virus entry, viral cDNA integration, and the production of infectious virus. Conclusion These results further suggest that the development of transgenic cotton rats expressing human HIV-1 receptors may prove to be useful small animal model for HIV infection.

  11. HIV sequence diversity during the early phase of infection is associated with HIV DNA reductions during antiretroviral therapy.

    Science.gov (United States)

    Wang, Nidan; Li, Yijia; Han, Yang; Xie, Jing; Li, Taisheng

    2017-06-01

    The association between baseline human immunodeficiency virus (HIV) sequence diversity and HIV DNA decay after the initiation of antiretroviral therapy (ART) remains uncharacterized during the early stages of HIV infection. Samples were obtained from a cohort of 17 patients with early HIV infection (HIV-1 envelope (env) gene was amplified via single genome amplification (SGA) to determine the peripheral plasma HIV quasispecies. We categorized HIV quasispecies into two groups according to baseline viral sequence genetic distance, which was determined by the Poisson-Fitter tool. Total HIV DNA in peripheral blood mononuclear cells (PBMCs), viral load, and T cell subsets were measured prior to and after the initiation of ART. The median SGA sequence number was 17 (range 6-28). At baseline, we identified 7 patients with homogeneous viral populations (designated the Homogeneous group) and 10 patients with heterogeneous viral populations (designated the Heterogeneous group) based on SGA sequences. Both groups exhibited similar HIV DNA decay rates during the first 6 months of ART (P > 0.99), but the Homogenous group experienced more prominent decay than the Heterogeneous group after 6 months (P = 0.037). The Heterogeneous group had higher CD4 cell counts after ART initiation; however, both groups had comparable recovery in terms of CD4/CD8 ratios and CD8 T cell activation levels. Viral population homogeneity upon the initiation of ART is associated with a decrease in HIV DNA levels during ART. J. Med. Virol. 89:982-988, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. HIV and smoking: associated risks and prevention strategies

    Directory of Open Access Journals (Sweden)

    Kariuki W

    2015-12-01

    Full Text Available Wanjiku Kariuki,1 Jennifer I Manuel,2 Ngaruiya Kariuki,3 Ellen Tuchman,2 Johnnie O'Neal,4 Genevieve A Lalanne2 1University of Texas School of Public Health, Department of Management, Policy, and Community Health, Houston, TX, 2Silver School of Social Work, New York University, New York, 3Internal Medicine Department, Maimonides Medical Center, Brooklyn, 4Department of Social Work, The College of New Rochelle, New Rochelle, NY, USA Abstract: High rates of smoking among persons living with HIV (PLWH may reduce the effectiveness of HIV treatment and contribute to significant morbidity and mortality. Factors associated with smoking in PLWH include mental health comorbidity, alcohol and drug use, health-related quality of life, smoking among social networks and supports, and lack of access to care. PLWH smokers are at a higher risk of numerous HIV-associated infections and non-HIV related morbidity, including a decreased response to antiretroviral treatment, impaired immune functioning, reduced cognitive functioning, decreased lung functioning, and cardiovascular disease. Seventeen smoking cessation interventions were identified, of which seven were randomized controlled trials. The most effective studies combined behavioral and pharmacotherapy treatments that incorporated comprehensive assessments, multiple sessions, and cognitive-behavioral and motivational strategies. Smoking cessation interventions that are tailored to the unique needs of diverse samples and incorporate strategies to reduce the risk of relapse are essential to advancing health outcomes in PLWH. Keywords: HIV, AIDS, smoking, health risks, smoking cessation interventions

  13. Modelling sexual transmission of HIV: testing the assumptions, validating the predictions

    Science.gov (United States)

    Baggaley, Rebecca F.; Fraser, Christophe

    2010-01-01

    Purpose of review To discuss the role of mathematical models of sexual transmission of HIV: the methods used and their impact. Recent findings We use mathematical modelling of “universal test and treat” as a case study to illustrate wider issues relevant to all modelling of sexual HIV transmission. Summary Mathematical models are used extensively in HIV epidemiology to deduce the logical conclusions arising from one or more sets of assumptions. Simple models lead to broad qualitative understanding, while complex models can encode more realistic assumptions and thus be used for predictive or operational purposes. An overreliance on model analysis where assumptions are untested and input parameters cannot be estimated should be avoided. Simple models providing bold assertions have provided compelling arguments in recent public health policy, but may not adequately reflect the uncertainty inherent in the analysis. PMID:20543600

  14. Fluorescent reporter signals, EGFP and DsRed, encoded in HIV-1 facilitate the detection of productively infected cells and cell-associated viral replication levels

    Directory of Open Access Journals (Sweden)

    Kazutaka eTerahara

    2012-01-01

    Full Text Available Flow cytometric analysis is a reliable and convenient method for investigating molecules at the single cell level. Previously, recombinant human immunodeficiency virus type 1 (HIV-1 strains were constructed that express a fluorescent reporter, either enhanced green fluorescent protein or DsRed, which allow the monitoring of HIV-1-infected cells by flow cytometry. The present study further investigated the potential of these recombinant viruses in terms of whether the HIV-1 fluorescent reporters would be helpful in evaluating viral replication based on fluorescence intensity. When primary CD4+ T cells were infected with recombinant viruses, the fluorescent reporter intensity measured by flow cytometry was associated with the level of CD4 downmodulation and Gag p24 expression in infected cells. Interestingly, some HIV-1-infected cells, in which CD4 was only moderately downmodulated, were reporter-positive but Gag p24-negative. Furthermore, when the activation status of primary CD4+ T cells was modulated by T cell receptor-mediated stimulation, we confirmed the preferential viral production upon strong stimulation and showed that the intensity of the fluorescent reporter within a proportion of HIV-1-infected cells was correlated with the viral replication level. These findings indicate that a fluorescent reporter encoded within HIV-1 is useful for the sensitive detection of productively-infected cells at different stages of infection and for evaluating cell-associated viral replication at the single cell level.

  15. Cell-associated HIV DNA measured early during infection has prognostic value independent of serum HIV RNA measured concomitantly

    DEFF Research Database (Denmark)

    Katzenstein, Terese L; Oliveri, Roberto S; Benfield, Thomas

    2002-01-01

    Using data from the Danish AIDS Cohort of HIV-infected homosexual men established in the 1980s, the prognostic value of early HIV DNA loads was evaluated. In addition to DNA measurements, concomitant serum HIV RNA levels, CD4 cell counts and CCR5 genotypes were determined. The patients were divided...... into 3 groups, according to whether their cell-associated HIV DNA load was or = 2,500 DNA copies/10(6) peripheral blood mononuclear cells. Clinical progression rates differed significantly between the groups (p value independent...... of serum HIV RNA (p value. Patients heterozygous for the CCR5 delta 32 allele had significantly lower HIV DNA loads than those homozygous for the normal allele (p

  16. Human cyclin T1 expression ameliorates a T-cell-specific transcriptional limitation for HIV in transgenic rats, but is not sufficient for a spreading infection of prototypic R5 HIV-1 strains ex vivo

    Directory of Open Access Journals (Sweden)

    Littman Dan R

    2009-01-01

    Full Text Available Abstract Background Cells derived from native rodents have limits at distinct steps of HIV replication. Rat primary CD4 T-cells, but not macrophages, display a profound transcriptional deficit that is ameliorated by transient trans-complementation with the human Tat-interacting protein Cyclin T1 (hCycT1. Results Here, we generated transgenic rats that selectively express hCycT1 in CD4 T-cells and macrophages. hCycT1 expression in rat T-cells boosted early HIV gene expression to levels approaching those in infected primary human T-cells. hCycT1 expression was necessary, but not sufficient, to enhance HIV transcription in T-cells from individual transgenic animals, indicating that endogenous cellular factors are critical co-regulators of HIV gene expression in rats. T-cells from hCD4/hCCR5/hCycT1-transgenic rats did not support productive infection of prototypic wild-type R5 HIV-1 strains ex vivo, suggesting one or more significant limitation in the late phase of the replication cycle in this primary rodent cell type. Remarkably, we identify a replication-competent HIV-1 GFP reporter strain (R7/3 YU-2 Env that displays characteristics of a spreading, primarily cell-to-cell-mediated infection in primary T-cells from hCD4/hCCR5-transgenic rats. Moreover, the replication of this recombinant HIV-1 strain was significantly enhanced by hCycT1 transgenesis. The viral determinants of this so far unique replicative ability are currently unknown. Conclusion Thus, hCycT1 expression is beneficial to de novo HIV infection in a transgenic rat model, but additional genetic manipulations of the host or virus are required to achieve full permissivity.

  17. HIV-Associated Lung Cancer.

    Science.gov (United States)

    Kiderlen, Til R; Siehl, Jan; Hentrich, Marcus

    2017-01-01

    Lung cancer (LC) is one of the most common non-AIDS (acquired immune deficiency syndrome)-defining malignancies. It occurs more frequently in persons living with human immunodeficiency virus (PLWHIV) than in the HIV-negative population. Compared to their HIV-negative counterparts, patients are usually younger and diagnosed at more advanced stages. The pathogenesis of LC in PLWHIV is not fully understood, but immunosuppression in combination with chronic infection and the oncogenic effects of smoking and HIV itself all seem to play a role. Currently, no established preventive screening is available, making smoking cessation the most promising preventive measure. Treatment protocols and standards are the same as for the general population. Notably, immuno-oncology will also become standard of care in a significant subset of HIV-infected patients with LC. As drug interactions and hematological toxicity must be taken into account, a multidisciplinary approach should include a physician experienced in the treatment of HIV. Only limited data is available on novel targeted therapies and checkpoint inhibitors in the setting of HIV. © 2017 S. Karger GmbH, Freiburg.

  18. Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans

    Directory of Open Access Journals (Sweden)

    Assaf Gottlieb

    2017-11-01

    Full Text Available Abstract Background Genome-wide association studies are useful for discovering genotype–phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into “gene level” effects. Methods Previous work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression—on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals. Results We build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations. Conclusions Our results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at https://github.com/assafgo/warfarin-cohort

  19. Multicohort Genomewide Association Study Reveals a New Signal of Protection Against HIV-1 Acquisition

    Science.gov (United States)

    Limou, Sophie; Delaneau, Olivier; van Manen, Daniëlle; An, Ping; Sezgin, Efe; Le Clerc, Sigrid; Coulonges, Cédric; Troyer, Jennifer L.; Veldink, Jan H.; van den Berg, Leonard H.; Spadoni, Jean-Louis; Taing, Lieng; Labib, Taoufik; Montes, Matthieu; Delfraissy, Jean-François; Schachter, François; O’Brien, Stephen J.; Buchbinder, Susan; van Natta, Mark L.; Jabs, Douglas A.; Froguel, Philippe; Schuitemaker, Hanneke; Winkler, Cheryl A.

    2012-01-01

    Background. To date, only mutations in CCR5 have been shown to confer resistance to human immunodeficiency virus type 1 (HIV-1) infection, and these explain only a small fraction of the observed variability in HIV susceptibility. Methods. We performed a meta-analysis between 2 independent European genomewide association studies, each comparing HIV-1 seropositive cases with normal population controls known to be HIV uninfected, to identify single-nucleotide polymorphisms (SNPs) associated with the HIV-1 acquisition phenotype. SNPs exhibiting P < 10−5 in this first stage underwent second-stage analysis in 2 independent US cohorts of European descent. Results. After the first stage, a single highly significant association was revealed for the chromosome 8 rs6996198 with HIV-1 acquisition and was replicated in both second-stage cohorts. Across the 4 groups, the rs6996198-T allele was consistently associated with a significant reduced risk of HIV-1 infection, and the global meta-analysis reached genomewide significance: Pcombined = 7.76 × 10−8. Conclusions. We provide strong evidence of association for a common variant with HIV-1 acquisition in populations of European ancestry. This protective signal against HIV-1 infection is the first identified outside the CCR5 nexus. First clues point to a potential functional role for a nearby candidate gene, CYP7B1, but this locus warrants further investigation. PMID:22362864

  20. Investigating the association between HIV/AIDS and recent fertility patterns in Kenya.

    Science.gov (United States)

    Magadi, Monica Akinyi; Agwanda, Alfred O

    2010-07-01

    Findings from previous studies linking the HIV/AIDS epidemic and fertility of populations have remained inconclusive. In sub-Saharan Africa, demographic patterns point to the epidemic resulting in fertility reduction. However, evidence from the 2003 Kenya Demographic and Health Survey (KDHS) has revealed interesting patterns, with regions most adversely affected with HIV/AIDS showing the clearest reversal trend in fertility decline. While there is suggestive evidence that fertility behaviour in some parts of sub-Saharan Africa has changed in relation to the HIV/AIDS epidemic, more rigorous empirical analysis is necessary to better understand this relationship. In this paper, we examine individual and contextual community HIV/AIDS factors associated with fertility patterns in Kenya, paying particular attention to possible mechanisms of the association. Multilevel models are applied to the 2003 KDHS, introducing various proximate fertility determinants in successive stages, to explore possible mechanisms through which HIV/AIDS may be associated with fertility. The results corroborate findings from earlier studies of the fertility inhibiting effect of HIV among infected women. HIV-infected women have 40 percent lower odds of having had a recent birth than their uninfected counterparts of similar background characteristics. Further analysis suggests an association between HIV/AIDS and fertility that exists through proximate fertility determinants relating to sexual exposure, breastfeeding duration, and foetal loss. While HIV/AIDS may have contributed to reduced fertility, mainly through reduced sexual exposure, there is evidence that it has contributed to increased fertility, through reduced breastfeeding and increased desire for more children resulting from increased infant/child mortality (i.e. a replacement phenomenon). In communities at advanced stages of the HIV/AIDS epidemic, it is possible that infant/child mortality has reached appreciably high levels where the

  1. Increased Expression of microRNA-17 Predicts Poor Prognosis in Human Glioma

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    Shengkui Lu

    2012-01-01

    Full Text Available Aim. To investigate the clinical significance of microRNA-17 (miR-17 expression in human gliomas. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR analysis was used to characterize the expression patterns of miR-17 in 108 glioma and 20 normal brain tissues. The associations of miR-17 expression with clinicopathological factors and prognosis of glioma patients were also statistically analyzed. Results. Compared with normal brain tissues, miR-17 expression was significantly higher in glioma tissues (P<0.001. In addition, the increased expression of miR-17 in glioma was significantly associated with advanced pathological grade (P=0.006 and low Karnofsky performance score (KPS, P=0.01. Moreover, Kaplan-Meier survival and Cox regression analyses showed that miR-17 overexpression (P=0.008 and advanced pathological grade (P=0.02 were independent factors predicting poor prognosis for gliomas. Furthermore, subgroup analyses showed that miR-17 expression was significantly associated with poor overall survival in glioma patients with high pathological grades (for grade III~IV: P<0.001. Conclusions. Our data offer the convinced evidence that the increased expression of miR-17 may have potential value for predicting poor prognosis in glioma patients with high pathological grades, indicating that miR-17 may contribute to glioma progression and be a candidate therapeutic target for this disease.

  2. HIV-associated vasculopathy

    African Journals Online (AJOL)

    Third World countries. HIV has brought an array of new clinical presentations and has also generated new syndromes.4. HIV vasculopathy was first described as an entity in 19875 and may ..... The EGF pathway is also implicated in cancer, which suggests that anticancer drugs that interfere with this pathway might increase.

  3. Strong association between in-migration and HIV prevalence in urban sub-Saharan Africa.

    Science.gov (United States)

    Voeten, Hélène A C M; Vissers, Debby C J; Gregson, Simon; Zaba, Basia; White, Richard G; de Vlas, Sake J; Habbema, J Dik F

    2010-04-01

    Enormous variation exists in HIV prevalence between countries in sub-Saharan Africa. The contribution of migration to the spread of HIV has long been recognized, but its effect at the population level has never been assessed. In this ecological analysis, we explore how much variation in HIV prevalence in urban sub-Saharan Africa is explained by in-migration. We performed a linear regression to analyze the association between the proportion of recent in-migrants and HIV prevalence for men and women in urban areas, using 60 data points from 28 sub-Saharan African countries between 1987 and 2005. We found a strong association between recent in-migration and HIV prevalence for women (Pearson R = 57%, P Africa (R = 50%, P = 0.003). For both genders, the association was strongest between 1985 and 1994, slightly weaker between 1995 and 1999, and nonexistent as from 2000. The overall association for both men and women was not confounded by the developmental indicators GNI per capita, income inequalities, or adult literacy. Migration explains much of the variation in HIV spread in urban areas of sub-Saharan Africa, especially before the year 2000, after which HIV prevalences started to level off in many countries. Our findings suggest that migration is an important factor in the spread of HIV, especially in rapidly increasing epidemics. This may be of relevance to the current HIV epidemics in China and India.

  4. Factors Associated with Length of Hospital Stay among HIV Positive and HIV Negative Patients with Tuberculosis in Brazil

    Science.gov (United States)

    Gonçalves, Maria Jacirema Ferreira; Ferreira, Alaidistania A.

    2013-01-01

    Objective Identify and analyze the factors associated to length of hospital stay among HIV positive and HIV negative patients with tuberculosis in Manaus city, state of Amazonas, Brazil, in 2010. Methods Epidemiological study with primary data obtained from monitoring of hospitalized patients with tuberculosis in Manaus. Data were collected by interviewing patients and analyzing medical records, according to the following study variables age, sex, co-morbidities, education, race, income, lifestyle, history of previous treatment or hospitalization due to tuberculosis, treatment regimen, adverse reactions, smear test, clinical form, type of discharge, and length of hospital stay. The associated factors were identified through chi-square or t-Student test at a 5% significance level. Results Income from 1 to 3 minimum wages (P = 0.028), pulmonary tuberculosis form (P = 0.011), negative smear test or no information in this regard (P = 0.014), initial 6-month treatment scheme (P = 0.029), and adverse drug reactions (P = 0.021) were associated to prolonged hospital stay in HIV positive patients. Conclusion We found out that although there were no significant differences in the length of hospital stay in HIV positive patients, all factors significantly associated to prolonged hospital stay occurred in this group of patients. This finding corroborates other studies indicating the severity of tuberculosis in HIV patients, which may also contribute to lengthen their hospital stay. PMID:23593227

  5. Physiotherapy management of patients with HIV-associated Kaposi's sarcoma.

    Science.gov (United States)

    Harris-Love, Michael O; Shrader, Joseph A

    2004-01-01

    Kaposi's sarcoma is the most common form of cancer in patients with human immunodeficiency virus (HIV) infection. Although Kaposi sarcoma lesions may contribute to significant physical impairments, there is a lack of scientific literature detailing the role of physiotherapy in the treatment of HIV-associated Kaposi's sarcoma. The present Case Report includes two males, aged 36 and 39 years, seropositive for HIV with invasive Kaposi's sarcoma. Patient A was evaluated for bilateral foot pain caused by plantar surface Kaposi s sarcoma lesions that rendered him unable to walk. He progressed to walking 400feet after a treatment regimen of gait training with the use of custom plastazote sandals. Patient B was evaluated for right lower extremity lymphoedema secondary to invasive Kaposi's sarcoma. He experienced an 18% reduction in limb volume, a 38% reduction in pain and a 20 degrees increase in terminal knee flexion after therapeutic exercise and the use of compressive bandaging and garments. This Case Report suggests that physiotherapy interventions may be valuable in the conservative management of patients with HIV-associated Kaposi s sarcoma.

  6. CD147 expression predicts biochemical recurrence after prostatectomy independent of histologic and pathologic features

    International Nuclear Information System (INIS)

    Bauman, Tyler M.; Ewald, Jonathan A.; Huang, Wei; Ricke, William A.

    2015-01-01

    CD147 is an MMP-inducing protein often implicated in cancer progression. The purpose of this study was to investigate the expression of CD147 in prostate cancer (PCa) progression and the prognostic ability of CD147 in predicting biochemical recurrence after prostatectomy. Plasma membrane-localized CD147 protein expression was quantified in patient samples using immunohistochemistry and multispectral imaging, and expression was compared to clinico-pathological features (pathologic stage, Gleason score, tumor volume, preoperative PSA, lymph node status, surgical margins, biochemical recurrence status). CD147 specificity and expression were confirmed with immunoblotting of prostate cell lines, and CD147 mRNA expression was evaluated in public expression microarray datasets of patient prostate tumors. Expression of CD147 protein was significantly decreased in localized tumors (pT2; p = 0.02) and aggressive PCa (≥pT3; p = 0.004), and metastases (p = 0.001) compared to benign prostatic tissue. Decreased CD147 was associated with advanced pathologic stage (p = 0.009) and high Gleason score (p = 0.02), and low CD147 expression predicted biochemical recurrence (HR 0.55; 95 % CI 0.31–0.97; p = 0.04) independent of clinico-pathologic features. Immunoblot bands were detected at 44 kDa and 66 kDa, representing non-glycosylated and glycosylated forms of CD147 protein, and CD147 expression was lower in tumorigenic T10 cells than non-tumorigenic BPH-1 cells (p = 0.02). Decreased CD147 mRNA expression was associated with increased Gleason score and pathologic stage in patient tumors but is not associated with recurrence status. Membrane-associated CD147 expression is significantly decreased in PCa compared to non-malignant prostate tissue and is associated with tumor progression, and low CD147 expression predicts biochemical recurrence after prostatectomy independent of pathologic stage, Gleason score, lymph node status, surgical margins, and tumor volume in multivariable

  7. Absolute leukocyte telomere length in HIV-infected and uninfected individuals: evidence of accelerated cell senescence in HIV-associated chronic obstructive pulmonary disease.

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    Joseph C Y Liu

    Full Text Available Combination antiretroviral therapy (cART has extended the longevity of human immunodeficiency virus (HIV-infected individuals. However, this has resulted in greater awareness of age-associated diseases such as chronic obstructive pulmonary disease (COPD. Accelerated cellular senescence may be responsible, but its magnitude as measured by leukocyte telomere length is unknown and its relationship to HIV-associated COPD has not yet been established. We measured absolute telomere length (aTL in peripheral leukocytes from 231 HIV-infected adults. Comparisons were made to 691 HIV-uninfected individuals from a population-based sample. Subject quartiles of aTL were assessed for relationships with measures of HIV disease severity, airflow obstruction, and emphysema severity on computed tomographic (CT imaging. Multivariable regression models identified factors associated with shortened aTL. Compared to HIV-uninfected subjects, the mean aTL in HIV-infected patients was markedly shorter by 27 kbp/genome (p<0.001; however, the slopes of aTL vs. age were not different (p=0.469. Patients with longer known durations of HIV infection (p=0.019 and lower nadir CD4 cell counts (p=0.023 had shorter aTL. Shorter aTL were also associated with older age (p=0.026, smoking (p=0.005, reduced forced expiratory volume in one second (p=0.030, and worse CT emphysema severity score (p=0.049. HIV-infected subjects demonstrate advanced cellular aging, yet in a cART-treated cohort, the relationship between aTL and age appears no different from that of HIV-uninfected subjects.

  8. Regulatory CD4 T cells inhibit HIV-1 expression of other CD4 T cell subsets via interactions with cell surface regulatory proteins.

    Science.gov (United States)

    Zhang, Mingce; Robinson, Tanya O; Duverger, Alexandra; Kutsch, Olaf; Heath, Sonya L; Cron, Randy Q

    2018-03-01

    During chronic HIV-1 infection, regulatory CD4 T cells (Tregs) frequently represent the largest subpopulation of CD4 T cell subsets, implying relative resistant to HIV-1. When HIV-1 infection of CD4 T cells was explored in vitro and ex vivo from patient samples, Tregs possessed lower levels of HIV-1 DNA and RNA in comparison with conventional effector and memory CD4 T cells. Moreover, Tregs suppressed HIV-1 expression in other CD4 T cells in an in vitro co-culture system. This suppression was mediated in part via multiple inhibitory surface proteins expressed on Tregs. Antibody blockade of CTLA-4, PD-1, and GARP on Tregs resulted in increased HIV-1 DNA integration and mRNA expression in neighboring CD4 T cells. Moreover, antibody blockade of Tregs inhibitory proteins resulted in increased HIV-1 LTR transcription in co-cultured CD4 T cells. Thus, Tregs inhibit HIV-1 infection of other CD4 T cell subsets via interactions with inhibitory cell surface proteins. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Use of human papillomavirus DNA, E6/E7 mRNA, and p16 immunocytochemistry to detect and predict anal high-grade squamous intraepithelial lesions in HIV-positive and HIV-negative men who have sex with men.

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    Nittaya Phanuphak

    Full Text Available Men who have sex with men (MSM are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV infection and HPV-mediated cell transformation to detect and predict HSIL among HIV-positive and HIV-negative MSM.A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled and followed for 12 months. High-resolution anoscopy (HRA with biopsies were performed at every visit along with anal sample collection for cytology, high-risk HPV DNA genotyping, HPV E6/E7 mRNA, and p16 immunocytochemistry. Performance characteristics and area under the receiver operator characteristics curve were calculated for these biomarkers at baseline, and Cox regression compared the usefulness of these biomarkers in predicting incident HSIL. High-risk HPV DNA, E6/E7 mRNA, and p16 immunocytochemistry each identified 43-46% of MSM whose baseline test positivity would trigger HRA referral. E6/E7 mRNA had the highest sensitivity (64.7% and correctly classified the highest number of prevalent HSIL cases. With the exception of p16 immunochemistry, most tests showed significant increases in sensitivity but decreases specificity versus anal cytology, while the overall number of correctly classified cases was not significantly different. Baseline or persistent type 16 and/or 18 HPV DNA was the only test significantly predicting incident histologic HSIL within 12 months in models adjusted for HIV status and low-grade squamous intraepithelial lesions at baseline.Countries with a high HIV prevalence among MSM and limited HRA resources may consider using biomarkers to identify individuals at high risk of HSIL. E6/E7 mRNA had the highest sensitivity for prevalent HSIL detection regardless of HIV status, whereas type 16 and/or 18 HPV DNA performed best in predicting development of incident HSIL within 12 months.

  10. Fibroblast growth factors 1 and 2 in cerebrospinal fluid are associated with HIV disease, methamphetamine use, and neurocognitive functioning

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    Bharti AR

    2016-04-01

    in five of seven cognitive domains, more than FGF-2, MCP-1, or neopterin. Conclusion: These findings provide in vivo support that HIV and MAD alter expression of FGFs, which may contribute to the NC abnormalities associated with these conditions. These cross-sectional findings cannot establish causality and the therapeutic benefits of recombinant FGF-1 need to be investigated. Keywords: biomarker, cerebrospinal fluid, fibroblast growth factor, HIV, methamphetamine, HIV-associated neurocognitive disorders, HAND, neurocognitive impairment

  11. Plasmacytoid dendritic cells accumulate and secrete interferon alpha in lymph nodes of HIV-1 patients.

    Directory of Open Access Journals (Sweden)

    Clara Lehmann

    2010-06-01

    Full Text Available Circulating plasmacytoid dendritic cells (pDC decline during HIV-1 infection, but at the same time they express markedly higher levels of interferon alpha (IFNalpha, which is associated with HIV-1 disease progression. Here we show an accumulation of pDC in lymph nodes (LN of treatment-naïve HIV-1 patients. This phenomenon was associated with elevated expression of the LN homing marker, CCR7, on pDC in peripheral blood of HIV-1 patients, which conferred increased migratory capacity in response to CCR7 ligands in ex vivo functional assays. LN-homed pDC of HIV-1 patients presented higher CD40 and lower BDCA2 levels, but unchanged CD83 and CD86 expression. In addition, these cells expressed markedly higher amounts of IFNalpha compared to uninfected individuals, and were undergoing faster rates of cell death. These results demonstrate for the first time that in asymptomatic, untreated HIV-1 patients circulating pDC up-regulate CCR7 expression, accumulate in lymph nodes, and express high amounts of IFNalpha before undergoing cell death. Since IFNalpha inhibits cell proliferation and modulates immune responses, chronically high levels of this cytokine in LN of HIV-1 patients may impair differentiation and immune function of bystander CD4(+ T cells, thus playing into the mechanisms of AIDS immunopathogenesis.

  12. Toll-like receptor 3 signalling up-regulates expression of the HIV co-receptor G-protein coupled receptor 15 on human CD4+ T cells.

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    Miriam Kiene

    Full Text Available BACKGROUND: Many HIV-2 and SIV isolates, as well as some HIV-1 strains, can use the orphan 7-transmembrane receptor GPR15 as co-receptor for efficient entry into host cells. GPR15 is expressed on central memory and effector memory CD4(+ T cells in healthy individuals and a subset of these cells is susceptible to HIV-1 and SIV infection. However, it has not been determined whether GPR15 expression is altered in the context of HIV-1 infection. RESULTS: Here, we show that GPR15 expression in CD4(+ T cells is markedly up-regulated in some HIV-1 infected individuals compared to the rest of the infected patients and to healthy controls. Infection of the PM1 T cell line with primary HIV-1 isolates was found to up-regulate GPR15 expression on the infected cells, indicating that viral components can induce GPR15 expression. Up-regulation of GPR15 expression on CD4(+ T cells was induced by activation of Toll-like receptor 3 signalling via TIR-domain-containing adapter-inducing interferon-β (TRIF and was more prominent on gut-homing compared to lymph node-homing CD4(+ T cells. CONCLUSION: These results suggest that infection-induced up-regulation of GPR15 expression could increase susceptibility of CD4(+ T cells to HIV infection and target cell availability in the gut in some infected individuals.

  13. Prevalence and associated factors of TB/HIV co-infection among HIV ...

    African Journals Online (AJOL)

    Abstract. Background: Tuberculosis is one of the world's most common causes of death in the era of Human immunodeficiency virus. The purpose of this study was to determine the prevalence and associated factors of TB/HIV co-infection. Methods: Hospital based retrospective studies were conducted among adult ...

  14. Factors Associated with Variations in Population HIV Prevalence across West Africa: Findings from an Ecological Analysis

    Science.gov (United States)

    Prudden, Holly J.; Beattie, Tara S.; Bobrova, Natalia; Panovska-Griffiths, Jasmina; Mukandavire, Zindoga; Gorgens, Marelize; Wilson, David; Watts, Charlotte H.

    2015-01-01

    Background Population HIV prevalence across West Africa varies substantially. We assess the national epidemiological and behavioural factors associated with this. Methods National, urban and rural data on HIV prevalence, the percentage of younger (15–24) and older (25–49) women and men reporting multiple (2+) partners in the past year, HIV prevalence among female sex workers (FSWs), men who have bought sex in the past year (clients), and ART coverage, were compiled for 13 countries. An Ecological analysis using linear regression assessed which factors are associated with national variations in population female and male HIV prevalence, and with each other. Findings National population HIV prevalence varies between 0 4–2 9% for men and 0 4–5.6% for women. ART coverage ranges from 6–23%. National variations in HIV prevalence are not shown to be associated with variations in HIV prevalence among FSWs or clients. Instead they are associated with variations in the percentage of younger and older males and females reporting multiple partners. HIV prevalence is weakly negatively associated with ART coverage, implying it is not increased survival that is the cause of variations in HIV prevalence. FSWs and younger female HIV prevalence are associated with client population sizes, especially older men. Younger female HIV prevalence is strongly associated with older male and female HIV prevalence. Interpretation In West Africa, population HIV prevalence is not significantly higher in countries with high FSW HIV prevalence. Our analysis suggests, higher prevalence occurs where more men buy sex, and where a higher percentage of younger women, and older men and women have multiple partnerships. If a sexual network between clients and young females exists, clients may potentially bridge infection to younger females. HIV prevention should focus both on commercial sex and transmission between clients and younger females with multiple partners. PMID:26698854

  15. Factors Associated with Variations in Population HIV Prevalence across West Africa: Findings from an Ecological Analysis.

    Directory of Open Access Journals (Sweden)

    Holly J Prudden

    Full Text Available Population HIV prevalence across West Africa varies substantially. We assess the national epidemiological and behavioural factors associated with this.National, urban and rural data on HIV prevalence, the percentage of younger (15-24 and older (25-49 women and men reporting multiple (2+ partners in the past year, HIV prevalence among female sex workers (FSWs, men who have bought sex in the past year (clients, and ART coverage, were compiled for 13 countries. An Ecological analysis using linear regression assessed which factors are associated with national variations in population female and male HIV prevalence, and with each other.National population HIV prevalence varies between 0 4-2 9% for men and 0 4-5.6% for women. ART coverage ranges from 6-23%. National variations in HIV prevalence are not shown to be associated with variations in HIV prevalence among FSWs or clients. Instead they are associated with variations in the percentage of younger and older males and females reporting multiple partners. HIV prevalence is weakly negatively associated with ART coverage, implying it is not increased survival that is the cause of variations in HIV prevalence. FSWs and younger female HIV prevalence are associated with client population sizes, especially older men. Younger female HIV prevalence is strongly associated with older male and female HIV prevalence.In West Africa, population HIV prevalence is not significantly higher in countries with high FSW HIV prevalence. Our analysis suggests, higher prevalence occurs where more men buy sex, and where a higher percentage of younger women, and older men and women have multiple partnerships. If a sexual network between clients and young females exists, clients may potentially bridge infection to younger females. HIV prevention should focus both on commercial sex and transmission between clients and younger females with multiple partners.

  16. Ecological association between HIV and concurrency point-prevalence in South Africa's ethnic groups.

    Science.gov (United States)

    Kenyon, Chris

    2013-11-01

    HIV prevalence between different ethnic groups within South Africa exhibits considerable variation. Numerous authors believe that elevated sexual partner concurrency rates are important in the spread of HIV. Few studies have, however, investigated if differential concurrency rates could explain differential HIV spread within ethnic groups in South Africa. This ecological analysis, explores how much of the variation in HIV prevalence by ethnic group is explained by differential concurrency rates. Using a nationally representative survey (the South African National HIV Prevalence, HIV Incidence, Behaviour and Communication Survey, 2005) the HIV prevalence in each of eight major ethnic groups was calculated. Linear regression analysis was used to assess the association between an ethnic group's HIV prevalence and the point-prevalence of concurrency. Results showed that HIV prevalence rates varied considerably between South Africa's ethnic groups. This applied to both different racial groups and to different ethnic groups within the black group. The point-prevalence of concurrency by ethnic group was strongly associated with HIV prevalence (R(2) = 0.83; p = 0.001). Tackling the key drivers of high HIV transmission in this population may benefit from more emphasis on partner reduction interventions.

  17. Genome-wide expression profiling analysis to identify key genes in the anti-HIV mechanism of CD4+ and CD8+ T cells.

    Science.gov (United States)

    Gao, Lijie; Wang, Yunqi; Li, Yi; Dong, Ya; Yang, Aimin; Zhang, Jie; Li, Fengying; Zhang, Rongqiang

    2018-07-01

    Comprehensive bioinformatics analyses were performed to explore the key biomarkers in response to HIV infection of CD4 + and CD8 + T cells. The numbers of CD4 + and CD8 + T cells of HIV infected individuals were analyzed and the GEO database (GSE6740) was screened for differentially expressed genes (DEGs) in HIV infected CD4 + and CD8 + T cells. Gene Ontology enrichment, KEGG pathway analyses, and protein-protein interaction (PPI) network were performed to identify the key pathway and core proteins in anti-HIV virus process of CD4 + and CD8 + T cells. Finally, we analyzed the expressions of key proteins in HIV-infected T cells (GSE6740 dataset) and peripheral blood mononuclear cells(PBMCs) (GSE511 dataset). 1) CD4 + T cells counts and ratio of CD4 + /CD8 + T cells decreased while CD8 + T cells counts increased in HIV positive individuals; 2) 517 DEGs were found in HIV infected CD4 + and CD8 + T cells at acute and chronic stage with the criterial of P-value T cells. The main biological processes of the DEGs were response to virus and defense response to virus. At chronic stage, ISG15 protein, in conjunction with IFN-1 pathway might play key roles in anti-HIV responses of CD4 + T cells; and 4) The expression of ISG15 increased in both T cells and PBMCs after HIV infection. Gene expression profile of CD4 + and CD8 + T cells changed significantly in HIV infection, in which ISG15 gene may play a central role in activating the natural antiviral process of immune cells. © 2018 Wiley Periodicals, Inc.

  18. A neuropsychological investigation of multitasking in HIV infection: implications for everyday functioning.

    Science.gov (United States)

    Scott, J Cobb; Woods, Steven Paul; Vigil, Ofilio; Heaton, Robert K; Schweinsburg, Brian C; Ellis, Ronald J; Grant, Igor; Marcotte, Thomas D

    2011-07-01

    A subset of individuals with HIV-associated neurocognitive impairment experience related deficits in "real world" functioning (i.e., independently performing instrumental activities of daily living [IADL]). While performance-based tests of everyday functioning are reasonably sensitive to HIV-associated IADL declines, questions remain regarding the extent to which these tests' highly structured nature fully captures the inherent complexities of daily life. The aim of this study was to assess the predictive and ecological validity of a novel multitasking measure in HIV infection. Participants included 60 individuals with HIV infection (HIV+) and 25 demographically comparable seronegative adults (HIV-). Participants were administered a comprehensive neuropsychological battery, questionnaires assessing mood and everyday functioning, and a novel standardized test of multitasking, which involved balancing the demands of four interconnected performance-based functional tasks (i.e., financial management, cooking, medication management, and telephone communication). HIV+ individuals demonstrated significantly worse overall performance, fewer simultaneous task attempts, and increased errors on the multitasking test as compared to the HIV- group. Within the HIV+ sample, multitasking impairments were modestly associated with deficits on standard neuropsychological measures of executive functions, episodic memory, attention/working memory, and information processing speed, providing preliminary evidence for convergent validity. More importantly, multivariate prediction models revealed that multitasking deficits were uniquely predictive of IADL dependence beyond the effects of depression and global neurocognitive impairment, with excellent sensitivity (86%), but modest specificity (57%). Taken together, these data indicate that multitasking ability may play an important role in successful everyday functioning in HIV+ individuals. PsycINFO Database Record (c) 2011 APA, all rights

  19. Utility of urine lipoarabinomannan (LAM) in diagnosing tuberculosis and predicting mortality with and without HIV: prospective TB cohort from the Thailand Big City TB Research Network.

    Science.gov (United States)

    Suwanpimolkul, Gompol; Kawkitinarong, Kamon; Manosuthi, Weerawat; Sophonphan, Jiratchaya; Gatechompol, Sivaporn; Ohata, Pirapon June; Ubolyam, Sasiwimol; Iampornsin, Thatri; Katerattanakul, Pairaj; Avihingsanon, Anchalee; Ruxrungtham, Kiat

    2017-06-01

    To evaluate the applicability and accuracy of the urine lipoarabinomannan (LAM) test in tuberculosis (TB)/HIV co-infected patients and HIV-negative patients with disseminated TB. Frozen urine samples obtained at baseline from patients in the TB research cohort with proven culture-positive TB were selected for blinded urine LAM testing. One hundred and nine patients were categorized into four groups: (1) HIV-positive patients with TB; (2) HIV-negative patients with disseminated TB; (3) HIV-negative immunocompromised patients with TB; and (4) patients with diseases other than TB. The sensitivity of urine LAM testing for culture-positive TB, specificity of urine LAM testing for patients without TB, positive predictive value (PPV), and negative predictive value (NPV) were assessed. The sensitivity of the urine LAM test in group 1 patients with a CD4 T-cell count of >100, ≤100, and ≤50 cells/mm 3 was 38.5%, 40.6%, and 45%, respectively. The specificity and PPV of the urine LAM test were >80%. The sensitivity of the test was 20% in group 2 and 12.5% in group 3, and the specificity and PPV were 100% for both groups. A positive urine LAM test result was significantly associated with death. This promising diagnostic tool could increase the yield of TB diagnosis and may predict the mortality rate of TB infection, particularly in TB/HIV co-infected patients. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  20. Microarray analysis of HIV resistant female sex workers reveal a gene expression signature pattern reminiscent of a lowered immune activation state.

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    Elijah M Songok

    Full Text Available To identify novel biomarkers for HIV-1 resistance, including pathways that may be critical in anti-HIV-1 vaccine design, we carried out a gene expression analysis on blood samples obtained from HIV-1 highly exposed seronegatives (HESN from a commercial sex worker cohort in Nairobi and compared their profiles to HIV-1 negative controls. Whole blood samples were collected from 43 HIV-1 resistant sex workers and a similar number of controls. Total RNA was extracted and hybridized to the Affymetrix HUG 133 Plus 2.0 micro arrays (Affymetrix, Santa Clara CA. Output data was analysed through ArrayAssist software (Agilent, San Jose CA. More than 2,274 probe sets were differentially expressed in the HESN as compared to the control group (fold change ≥1.3; p value ≤0.0001, FDR <0.05. Unsupervised hierarchical clustering of the differentially expressed genes readily distinguished HESNs from controls. Pathway analysis through the KEGG signaling database revealed a majority of the impacted pathways (13 of 15, 87% had genes that were significantly down regulated. The most down expressed pathways were glycolysis/gluconeogenesis, pentose phosphate, phosphatidyl inositol, natural killer cell cytotoxicity and T-cell receptor signaling. Ribosomal protein synthesis and tight junction genes were up regulated. We infer that the hallmark of HIV-1 resistance is down regulation of genes in key signaling pathways that HIV-1 depends on for infection.

  1. Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression.

    Directory of Open Access Journals (Sweden)

    Robert M Paris

    Full Text Available The role of PD-1 expression on CD4 T cells during HIV infection is not well understood. Here, we describe the differential expression of PD-1 in CD127high CD4 T cells within the early/intermediate differentiated (EI (CD27highCD45RAlow T cell population among uninfected and HIV-infected subjects, with higher expression associated with decreased viral replication (HIV-1 viral load. A significant loss of circulating PD-1highCTLA-4low CD4 T cells was found specifically in the CD127highCD27highCD45RAlow compartment, while initiation of antiretroviral treatment, particularly in subjects with advanced disease, reversed these dynamics. Increased HIV-1 Gag DNA was also found in PD-1high compared to PD-1low ED CD4 T cells. In line with an increased susceptibility to HIV infection, PD-1 expression in this CD4 T cell subset was associated with increased activation and expression of the HIV co-receptor, CCR5. Rather than exhaustion, this population produced more IFN-g, MIP1-a, IL-4, IL-10, and IL-17a compared to PD-1low EI CD4 T cells. In line with our previous findings, PD-1high EI CD4 T cells were also characterized by a high expression of CCR7, CXCR5 and CCR6, a phenotype associated with increased in vitro B cell help. Our data show that expression of PD-1 on early-differentiated CD4 T cells may represent a population that is highly functional, more susceptible to HIV infection and selectively lost in chronic HIV infection.

  2. Hepatic HMOX1 expression positively correlates with Bach-1 and miR-122 in patients with HCV mono and HIV/HCV coinfection.

    Science.gov (United States)

    Jabłonowska, Elżbieta; Wójcik, Kamila; Szymańska, Bożena; Omulecka, Aleksandra; Cwiklińska, Hanna; Piekarska, Anna

    2014-01-01

    To analyze the expression of HMOX1 and miR-122 in liver biopsy samples obtained from HCV mono-and HIV/HCV co-infected patients in relation to selected clinical parameters, histological examination and IL-28B polymorphism as well as to determine whether HMOX1 expression is dependent on Bach-1. The study group consisted of 90 patients with CHC: 69 with HCV mono and 21 with HIV/HCV co-infection. RT-PCR was used in the analysis of HMOX1, Bach-1 and miR-122 expression in liver biopsy samples and in the assessment of IL-28B single-nucleotide polymorphism C/T (rs12979860) in the blood. Moreover in liver biopsy samples an analysis of HO-1 and Bach-1 protein level by Western Blot was performed. HCV mono-infected patients, with lower grading score (G600000 IU/mL) demonstrated higher expression of HMOX1. In patients with HIV/HCV co-infection, the expression of HMOX1 was lower in patients with lower lymphocyte CD4 count and higher HIV viral load. IL28B polymorphism did not affect the expression of either HMOX1 or miR-122. Higher HMOX1 expression correlated with higher expression of Bach-1 (Spearman's ρ = 0.586, p = 0.000001) and miR-122 (Spearman's ρ = 0.270, p = 0.014059). HMOX1 and miR-122 play an important role in the pathogenesis of CHC in HCV mono-and HIV/HCV co-infected patients. Reduced expression of HMOX1 in patients with HIV/HCV co-infection may indicate a worse prognosis in this group. Our results do not support the importance of Bach-1 in repression of HMOX1 in patients with chronic hepatitis C.

  3. Validation of the International HIV Dementia Scale as a Screening Tool for HIV-Associated Neurocognitive Disorders in a German-Speaking HIV Outpatient Clinic.

    Directory of Open Access Journals (Sweden)

    Victor Marin-Webb

    Full Text Available HIV-associated neurocognitive disorders (HAND are widely present among people living with HIV. Especially its milder forms, asymptomatic neurocognitive impairment (ANI and mild neurocognitive disorder (MND, remain highly prevalent worldwide. Diagnosing these conditions is subject to a time and resource consuming neuropsychological assessment. Selecting patients at a higher risk of cognitive impairment by using a simple but effective screening tool helps to organise access to further neuropsychological diagnosis. The International HIV Dementia Scale (IHDS has until now been a well-established screening tool in African and American countries, however these populations' demographics defer significantly from ours, so using the same parameters could be ineffective.To calculate the prevalence of this condition among people attending an HIV outpatient clinic in Berlin and to validate the use of the IHDS as a screening tool for HAND in a German-speaking population.We screened 480 HIV-infected patients using the IHDS, 89% of them were on a stable antiretroviral treatment. Ninety of them completed a standardised neuropsychological battery of tests and a specific cognitive complaints questionnaire. The same procedure was applied to a control group of 30 HIV-negative participants. HAND diagnosis was established according to the Frascati criteria.The overall prevalence of HAND in our cohort was 43% (20% ANI, 17% MND and 6% HIV-associated dementia. The optimal cut-off on the IHDS for detecting HAND cases was set at 11 and achieved both a sensitivity and a specificity of 80%. When specifically screening for the more severe form of HAND, HIV-associated dementia, a cut-off value of 10 offered an increase in both sensitivity (94% and specificity (86%. The Youden Index for diagnostic accuracy was 0.6 and 0.8, respectively.The prevalence of HAND was comparable to the reported by recent studies performed in countries with a similar economic development. The study

  4. Validation of the International HIV Dementia Scale as a Screening Tool for HIV-Associated Neurocognitive Disorders in a German-Speaking HIV Outpatient Clinic.

    Science.gov (United States)

    Marin-Webb, Victor; Jessen, Heiko; Kopp, Ute; Jessen, Arne B; Hahn, Katrin

    2016-01-01

    HIV-associated neurocognitive disorders (HAND) are widely present among people living with HIV. Especially its milder forms, asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND), remain highly prevalent worldwide. Diagnosing these conditions is subject to a time and resource consuming neuropsychological assessment. Selecting patients at a higher risk of cognitive impairment by using a simple but effective screening tool helps to organise access to further neuropsychological diagnosis. The International HIV Dementia Scale (IHDS) has until now been a well-established screening tool in African and American countries, however these populations' demographics defer significantly from ours, so using the same parameters could be ineffective. To calculate the prevalence of this condition among people attending an HIV outpatient clinic in Berlin and to validate the use of the IHDS as a screening tool for HAND in a German-speaking population. We screened 480 HIV-infected patients using the IHDS, 89% of them were on a stable antiretroviral treatment. Ninety of them completed a standardised neuropsychological battery of tests and a specific cognitive complaints questionnaire. The same procedure was applied to a control group of 30 HIV-negative participants. HAND diagnosis was established according to the Frascati criteria. The overall prevalence of HAND in our cohort was 43% (20% ANI, 17% MND and 6% HIV-associated dementia). The optimal cut-off on the IHDS for detecting HAND cases was set at 11 and achieved both a sensitivity and a specificity of 80%. When specifically screening for the more severe form of HAND, HIV-associated dementia, a cut-off value of 10 offered an increase in both sensitivity (94%) and specificity (86%). The Youden Index for diagnostic accuracy was 0.6 and 0.8, respectively. The prevalence of HAND was comparable to the reported by recent studies performed in countries with a similar economic development. The study confirms

  5. Growth hormone and tesamorelin in the management of HIV-associated lipodystrophy

    Directory of Open Access Journals (Sweden)

    Bedimo R

    2011-07-01

    Full Text Available Roger BedimoInfectious Disease section, VA North Texas Health Care System, TX, USAAbstract: HIV-infected patients on highly active antiretroviral therapy (HAART develop a complex of body composition changes known, including peripheral fat loss (lipoatrophy and central fat accumulation (lipohypertrophy. These changes may cause significant patient distress, which could in turn interfere with adherence to antiretroviral therapy. Treatment options – including antiretroviral switch, insulin sensitizers, and surgical approaches – have been associated with limited success and potential complications. The observation that low growth hormone levels are associated with central fat accumulation among HIV patients has led to the development of tesamorelin (a growth hormone releasing hormone analog for the management of central fat accumulation. Randomized controlled trials have shown that administration of tesamorelin is safe and effective in reducing central fat accumulation among HIV-infected patients. This effect is transient, however, and its association with improved cardiovascular risk remains unclear.Keywords: HAART, HIV, tesamorelin, lipodystrophy

  6. Genome-wide association studies on HIV susceptibility, pathogenesis and pharmacogenomics

    Directory of Open Access Journals (Sweden)

    van Manen Daniëlle

    2012-08-01

    Full Text Available Abstract Susceptibility to HIV-1 and the clinical course after infection show a substantial heterogeneity between individuals. Part of this variability can be attributed to host genetic variation. Initial candidate gene studies have revealed interesting host factors that influence HIV infection, replication and pathogenesis. Recently, genome-wide association studies (GWAS were utilized for unbiased searches at a genome-wide level to discover novel genetic factors and pathways involved in HIV-1 infection. This review gives an overview of findings from the GWAS performed on HIV infection, within different cohorts, with variable patient and phenotype selection. Furthermore, novel techniques and strategies in research that might contribute to the complete understanding of virus-host interactions and its role on the pathogenesis of HIV infection are discussed.

  7. Measuring child awareness for adult symptomatic HIV using a verbal assessment tool: concordance between adult-child dyads on adult HIV-associated symptoms and illnesses.

    Science.gov (United States)

    Becker, Elisabeth; Kuo, Caroline; Operario, Don; Moshabela, Mosa; Cluver, Lucie

    2015-11-01

    This study assessed children's awareness for adult HIV-associated symptoms and illnesses using a verbal assessment tool by analysing inter-rater reliability between adult-child dyads. This study also evaluated sociodemographic and household characteristics associated with child awareness of adult symptomatic HIV. A cross-sectional survey using a representative community sample of adult-child dyads (N=2477 dyads) was conducted in KwaZulu-Natal, South Africa. Analyses focused on a subsample (n=673 adult-child dyads) who completed verbal assessment interviews for symptomatic HIV. We used an existing validated verbal autopsy approach, originally designed to determine AIDS-related deaths by adult proxy reporters. We adapted this approach for use by child proxy reporters for reporting on HIV-associated symptoms and illnesses among living adults. Analyses assessed whether children could reliably report on adult HIV-associated symptoms and illnesses and adult provisional HIV status. Adult-child pairs concurred above the 65th percentile for 9 of the 10 HIV-associated symptoms and illnesses with sensitivities ranging from 10% to 100% and specificities ranging from 20% to 100%. Concordant reporting between adult-child dyads for the adult's provisional HIV status was 72% (sensitivity=68%, specificity=73%). Children were more likely to reliably match adult's reports of provisional HIV status when they lived in households with more household members, and households with more robust socioeconomic indicators including access to potable water, food security and television. Children demonstrate awareness of HIV-associated symptoms and illnesses experienced by adults in their household. Children in households with greater socioeconomic resources and more household members were more likely to reliably report on the adult's provisional HIV status. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Validity of impedance-based predictions of total body water as measured by 2H dilution in African HIV/AIDS outpatients

    International Nuclear Information System (INIS)

    Diouf, Adama; Idohou Dossou, Nicole; Wade, Salimata; Gartner, Agnes; Sanon, Dominique Alexis; Bluck, Les; Wright, Antony

    2009-01-01

    Measurements of body composition are crucial in identifying HIV-infected patients at risk of malnutrition. No information is available on the validity of indirect body composition methods in African HIV-infected outpatients. Our aim was to test the validity of fifteen published equations, developed in whites, African-Americans and/or Africans who were or not HIV-infected, for predicting total body water (TBW) from bioelectrical impedance analysis (BIA) in HIV-infected patients. The second aim was to develop specific predictive equations. Thirty-four HIV-infected patients without antiretroviral treatment and oedema at the beginning of the study (age 39 (SD 7) years, BMI 18.7 (SD 3.7) kg/m2, TBW 30.4 (SD 7.2 kg) were measured at inclusion then 3 and 6 months later. In the resulting eighty-eight measurements, we compared TBW values predicted from BIA to those measured by 2H dilution. Range of bias values was 0.1-4.3, and errors showed acceptable values (2.2-3.4 kg) for fourteen equations and a high value (10.4) for one equation. Two equations developed in non-HIV-infected subjects showed non-significant bias and could be used in African HIV-infected patients. In the other cases, poor agreement indicated a lack of validity. Specific equations developed from our sample showed a higher precision of TBW prediction when using resistance at 1000kHz (1.7kg) than at 50kHz (2.3kg), this latter precision being similar to that of the valid published equations (2.3 and 2.8kg). The valid published or developed predictive equations should be cross-validated in large independent samples of African HIV-infected patients. (Authors)

  9. Pulmonary symptoms and diagnoses are associated with HIV in the MACS and WIHS cohorts.

    Science.gov (United States)

    Gingo, Matthew R; Balasubramani, Goundappa K; Rice, Thomas B; Kingsley, Lawrence; Kleerup, Eric C; Detels, Roger; Seaberg, Eric C; Greenblatt, Ruth M; Holman, Susan; Huang, Laurence; Sutton, Sarah H; Bertolet, Marnie; Morris, Alison

    2014-04-30

    Several lung diseases are increasingly recognized as comorbidities with HIV; however, few data exist related to the spectrum of respiratory symptoms, diagnostic testing, and diagnoses in the current HIV era. The objective of the study is to determine the impact of HIV on prevalence and incidence of respiratory disease in the current era of effective antiretroviral treatment. A pulmonary-specific questionnaire was administered yearly for three years to participants in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS). Adjusted prevalence ratios for respiratory symptoms, testing, or diagnoses and adjusted incidence rate ratios for diagnoses in HIV-infected compared to HIV-uninfected participants were determined. Risk factors for outcomes in HIV-infected individuals were modeled. Baseline pulmonary questionnaires were completed by 907 HIV-infected and 989 HIV-uninfected participants in the MACS cohort and by 1405 HIV-infected and 571 HIV-uninfected participants in the WIHS cohort. In MACS, dyspnea, cough, wheezing, sleep apnea, and incident chronic obstructive pulmonary disease (COPD) were more common in HIV-infected participants. In WIHS, wheezing and sleep apnea were more common in HIV-infected participants. Smoking (MACS and WIHS) and greater body mass index (WIHS) were associated with more respiratory symptoms and diagnoses. While sputum studies, bronchoscopies, and chest computed tomography scans were more likely to be performed in HIV-infected participants, pulmonary function tests were no more common in HIV-infected individuals. Respiratory symptoms in HIV-infected individuals were associated with history of pneumonia, cardiovascular disease, or use of HAART. A diagnosis of asthma or COPD was associated with previous pneumonia. In these two cohorts, HIV is an independent risk factor for several respiratory symptoms and pulmonary diseases including COPD and sleep apnea. Despite a higher prevalence of chronic respiratory symptoms

  10. Epidemiology, Diagnosis, and Treatment of HIV-Associated Non-Hodgkin Lymphoma in Resource-Limited Settings

    Directory of Open Access Journals (Sweden)

    Matthew Ulrickson

    2012-01-01

    Full Text Available Lymphoma was a common complication of HIV infection in the pre-antiretroviral era, and the incidence of HIV-associated lymphoma has dropped dramatically since the introduction of combination antiretroviral therapy (cART in resource-rich regions. Conversely, lymphoma is an increasingly common complication of HIV infection in resource-limited settings where the prevalence of HIV infection is high. Relatively little is known, however, about the true incidence and optimal treatment regimens for HIV-associated lymphoma in resource-poor regions. We review the epidemiology, diagnosis, and treatment of HIV-associated non-Hodgkin lymphoma in developing nations and highlight areas for further research that may benefit care in both settings. Examples include risk modification and dose modification of chemotherapy based on HIV risk factors, improving our understanding of the current burden of disease through national cancer registries, and developing cost-effective hematopathological diagnostic strategies to optimize care delivery and maximize use of available chemotherapy.

  11. Associations between HIV-related stigma, racial discrimination, gender discrimination, and depression among HIV-positive African, Caribbean, and Black women in Ontario, Canada.

    Science.gov (United States)

    Logie, Carmen; James, Llana; Tharao, Wangari; Loutfy, Mona

    2013-02-01

    Abstract African, Caribbean, and Black (ACB) women are greatly overrepresented in new HIV infections in comparison with Canada's general population. Social and structural factors such as HIV-related stigma, gender discrimination, and racial discrimination converge to increase vulnerability to HIV infection among ACB women by reducing access to HIV prevention services. Stigma and discrimination also present barriers to treatment, care, and support and may contribute to mental health problems. We administered a cross-sectional survey to HIV-positive ACB women (n=173) across Ontario in order to examine the relationships between HIV-related stigma, gender discrimination, racial discrimination, and depression. One-third of participants reported moderate/severe depression scores using the Beck Depression Inventory Fast-Screen guidelines. Hierarchical block regression, moderation, and mediation analyses were conducted to measure associations between independent (HIV-related stigma, gender discrimination, racial discrimination), moderator/mediator (social support, resilient coping), and dependent (depression) variables. Findings included: (1) HIV-related stigma was associated with increased depression; (2) resilient coping was associated with reduced depression but did not moderate the influence of HIV-related stigma on depression; and (3) the effects of HIV-related stigma on depression were partially mediated through resilient coping. HIV-related stigma, gender discrimination, and racial discrimination were significantly correlated with one another and with depression, highlighting the salience of examining multiple intersecting forms of stigma. Generalizability of findings may be limited due to nonrandom sampling. Findings emphasize the importance of multi-component interventions, including building resilient coping skills, mental health promotion and assessment, and stigma reduction programs.

  12. HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell.

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    Mikaël Boullé

    2016-11-01

    Full Text Available Cell-to-cell spread of HIV, a directed mode of viral transmission, has been observed to be more rapid than cell-free infection. However, a mechanism for earlier onset of viral gene expression in cell-to-cell spread was previously uncharacterized. Here we used time-lapse microscopy combined with automated image analysis to quantify the timing of the onset of HIV gene expression in a fluorescent reporter cell line, as well as single cell staining for infection over time in primary cells. We compared cell-to-cell spread of HIV to cell-free infection, and limited both types of transmission to a two-hour window to minimize differences due to virus transit time to the cell. The mean time to detectable onset of viral gene expression in cell-to-cell spread was accelerated by 19% in the reporter cell line and by 35% in peripheral blood mononuclear cells relative to cell-free HIV infection. Neither factors secreted by infected cells, nor contact with infected cells in the absence of transmission, detectably changed onset. We recapitulated the earlier onset by infecting with multiple cell-free viruses per cell. Surprisingly, the acceleration in onset of viral gene expression was not explained by cooperativity between infecting virions. Instead, more rapid onset was consistent with a model where the fastest expressing virus out of the infecting virus pool sets the time for infection independently of the other co-infecting viruses.

  13. Adverse psychosocial factors predict poorer prognosis in HIV disease: a meta-analytic review of prospective investigations.

    Science.gov (United States)

    Chida, Yoichi; Vedhara, Kavita

    2009-05-01

    There is a growing epidemiological literature focusing on the association between psychosocial stress and human immunodeficiency virus (HIV) disease progression or acquired immunodeficiency syndrome (AIDS), but inconsistent findings have been published. We aimed to quantify the association between adverse psychosocial factors and HIV disease progression. We searched Medline; PsycINFO; Web of Science; PubMed up to 19 January 2009, and included population studies with a prospective design that investigated associations between adverse psychosocial factors and HIV disease progression or AIDS. Two reviewers independently extracted data on study characteristics, quality, and estimates of associations. The overall meta-analysis examined 36 articles including 100 psychosocial and disease related relationships. It exhibited a small, but robust positive association between adverse psychosocial factors and HIV progression (correlation coefficient as combined size effect 0.059, 95% confidence interval 0.043-0.074, p<0.001). Notably, sensitivity analyses showed that personality types or coping styles and psychological distress were more strongly associated with greater HIV disease progression than stress stimuli per se, and that all of the immunological and clinical outcome indicators (acquired immunodeficiency syndrome stage, CD4+ T-cell decline, acquired immunodeficiency syndrome diagnosis, acquired immunodeficiency syndrome mortality, and human immunodeficiency virus disease or acquired immunodeficiency syndrome symptoms) except for viral load exhibited detrimental effects by adverse psychosocial factors. In conclusion, the current review reveals a robust relationship between adverse psychosocial factors and HIV disease progression. Furthermore, there would appear to be some evidence for particular psychosocial factors to be most strongly associated with HIV disease progression.

  14. Outcome of HIV-1-associated cryptococcal meningitis, Denmark 1988-2008

    DEFF Research Database (Denmark)

    Mathiesen, Inger Hee Mabuza; Knudsen, Jenny Dahl; Gerstoft, Jan

    2012-01-01

    Abstract Introduction: The risk of HIV-1-associated Cryptococcus neoformans meningitis (CM) has decreased and the outcome has improved with the use of combination antiretroviral therapy (cART). Outcome has not been reported in Denmark in the cART era. Methods: A review of all cases of HIV-1...

  15. Disclosure appraisal mediating the association between perceived stigma and HIV disclosure to casual sex partners among HIV+ MSM: a path model analysis.

    Science.gov (United States)

    Li, Haochu; Chen, Xinguang; Yu, Bin

    2016-01-01

    HIV stigma is widely believed to be related to HIV disclosure. However, there is a dearth of studies examining the mechanisms that link stigma to disclosure. This is a specific study to assess the relationship between perceived stigma and HIV disclosure to casual sex partners based on a social cognitive theory. HIV+ men who have sex with men (MSM) from two US cities (N = 297) completed questionnaires administered using audio computer-assisted self-interviewing. Path modeling analysis was used to assess the theory-based structural relationships. Perceived stigma was negatively associated with attitudes, intention and behavior of HIV disclosure to casual sex partners. The association was fully mediated by disclosure appraisal, including disclosure outcome expectations, costs and self-efficacy. Findings of this study add new knowledge regarding HIV stigma and disclosure, and provide timely data supporting more effective behavioral interventions to encourage HIV disclosure among MSM.

  16. Clinical correlates of HIV-associated neurocognitive disorders in South Africa.

    Science.gov (United States)

    Joska, John A; Fincham, Dylan S; Stein, Dan J; Paul, Robert H; Seedat, Soraya

    2010-04-01

    Human immunodeficiency virus-associated neurocognitive disorders (HAND) occurs globally and across different genetic clades of the virus. However, few studies have examined HAND in South Africa, despite the prevalence of HIV in this region of the world, and the predominance of clade C. The present study examined the relationship between a number of demographic and clinical variables in a sample of 536 patients attending HIV clinics in South Africa. HAND was present in 23.5% of the sample and was associated with older age, a low educational level among those with post-traumatic stress disorder (PTSD) and alcohol abuse among those with many months since diagnosis. These results suggest that HAND is common among patients in South Africa, and is associated with clinical variables such as PTSD and alcohol abuse. This underlines the impact of HIV on the nervous system and the importance of screening for co morbid mental health conditions.

  17. Rapid High-Level Production of Functional HIV Broadly Neutralizing Monoclonal Antibodies in Transient Plant Expression Systems

    Science.gov (United States)

    Rosenberg, Yvonne; Sack, Markus; Montefiori, David; Forthal, Donald; Mao, Lingjun; -Abanto, Segundo Hernandez; Urban, Lori; Landucci, Gary; Fischer, Rainer; Jiang, Xiaoming

    2013-01-01

    Passive immunotherapy using anti-HIV broadly neutralizing monoclonal antibodies (mAbs) has shown promise as an HIV treatment, reducing mother-to-child-transmission (MTCT) of simian/human immunodeficiency virus (SHIV) in non-human primates and decreasing viral rebound in patients who ceased receiving anti-viral drugs. In addition, a cocktail of potent mAbs may be useful as mucosal microbicides and provide an effective therapy for post-exposure prophylaxis. However, even highly neutralizing HIV mAbs used today may lose their effectiveness if resistance occurs, requiring the rapid production of new or engineered mAbs on an ongoing basis in order to counteract the viral resistance or the spread of a certain HIV-1 clade in a particular region or patient. Plant-based expression systems are fast, inexpensive and scalable and are becoming increasingly popular for the production of proteins and monoclonal antibodies. In the present study, Agrobacterium-mediated transient transfection of plants, utilizing two species of Nicotiana, have been tested to rapidly produce high levels of an HIV 89.6PΔ140env and several well-studied anti-HIV neutralizing monoclonal antibodies (b12, 2G12, 2F5, 4E10, m43, VRC01) or a single chain antibody construct (m9), for evaluation in cell-based viral inhibition assays. The protein-A purified plant-derived antibodies were intact, efficiently bound HIV envelope, and were equivalent to, or in one case better than, their counterparts produced in mammalian CHO or HEK-293 cells in both neutralization and antibody dependent viral inhibition assays. These data indicate that transient plant-based transient expression systems are very adaptable and could rapidly generate high levels of newly identified functional recombinant HIV neutralizing antibodies when required. In addition, they warrant detailed cost-benefit analysis of prolonged incubation in plants to further increase mAb production. PMID:23533588

  18. Rapid high-level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems.

    Directory of Open Access Journals (Sweden)

    Yvonne Rosenberg

    Full Text Available Passive immunotherapy using anti-HIV broadly neutralizing monoclonal antibodies (mAbs has shown promise as an HIV treatment, reducing mother-to-child-transmission (MTCT of simian/human immunodeficiency virus (SHIV in non-human primates and decreasing viral rebound in patients who ceased receiving anti-viral drugs. In addition, a cocktail of potent mAbs may be useful as mucosal microbicides and provide an effective therapy for post-exposure prophylaxis. However, even highly neutralizing HIV mAbs used today may lose their effectiveness if resistance occurs, requiring the rapid production of new or engineered mAbs on an ongoing basis in order to counteract the viral resistance or the spread of a certain HIV-1 clade in a particular region or patient. Plant-based expression systems are fast, inexpensive and scalable and are becoming increasingly popular for the production of proteins and monoclonal antibodies. In the present study, Agrobacterium-mediated transient transfection of plants, utilizing two species of Nicotiana, have been tested to rapidly produce high levels of an HIV 89.6PΔ140env and several well-studied anti-HIV neutralizing monoclonal antibodies (b12, 2G12, 2F5, 4E10, m43, VRC01 or a single chain antibody construct (m9, for evaluation in cell-based viral inhibition assays. The protein-A purified plant-derived antibodies were intact, efficiently bound HIV envelope, and were equivalent to, or in one case better than, their counterparts produced in mammalian CHO or HEK-293 cells in both neutralization and antibody dependent viral inhibition assays. These data indicate that transient plant-based transient expression systems are very adaptable and could rapidly generate high levels of newly identified functional recombinant HIV neutralizing antibodies when required. In addition, they warrant detailed cost-benefit analysis of prolonged incubation in plants to further increase mAb production.

  19. Association of Pulmonary Tuberculosis and HIV in the Mexican Institute of Social Security, 2006-2014.

    Directory of Open Access Journals (Sweden)

    David Alejandro Cabrera-Gaytán

    Full Text Available Tuberculosis and HIV remain a public health problem in developed countries. The objective of this study was to analyze the incidence trends of pulmonary TB and HIV comorbidity and treatment outcomes according to HIV during the period 2006 to 2014 in the Mexican Institute of Social Security.Analyzed data from this registry including pulmonary tuberculosis patients aged 15 years and older who had been diagnosed during the years 2006 to 2014 in the Mexican Institute of Social Security. The outcomes that we use were incidents rate, failure to treatment and death. Regression models were used to quantify associations between pulmonary tuberculosis and HIV mortality.During the study period, 31,352 patients were registered with pulmonary tuberculosis. The incidence rate observed during 2014 was 11.6 case of PTB per 100,000. The incidence rate for PTB and HIV was 0.345 per 100,000. The PTB incidence rate decreased by 0.07%, differences found in the PTB incidence rate by sex since in women decreased by 5.52% and in man increase by 3.62%. The pulmonary TB with HIV incidence rate decreased by 16.3% during the study period (In women increase 4.81% and in man decrease 21.6%. Analysis of PTB associated with HIV by age groups revealed that the highest incidence rates were observed for the 30 to 44 years old group. Meanwhile, the highest incidence rates of PTB without HIV occurred among the 60 and more years old individuals. We did not find statistically significant differences between treatment failure and PTB patients with HIV and without HIV. The treatment failure was associated with sex and the region of the patient. We found a strong association between HIV and the probability of dying during treatment. Our data suggested that patients suffering from both conditions (PTB and HIV have no difference in the probability of failure of treatment contrary to other reports. Hypotheses to this is adherence to tuberculosis treatment with people living with HIV

  20. Association of Pulmonary Tuberculosis and HIV in the Mexican Institute of Social Security, 2006-2014.

    Science.gov (United States)

    Cabrera-Gaytán, David Alejandro; Niebla-Fuentes, María Del Rosario; Padilla-Velázquez, Rosario; Valle-Alvarado, Gabriel; Arriaga-Nieto, Lumumba; Rojas-Mendoza, Teresita; Rosado-Quiab, Ulises; Grajales-Muñiz, Concepción; Vallejos-Parás, Alfonso

    2016-01-01

    Tuberculosis and HIV remain a public health problem in developed countries. The objective of this study was to analyze the incidence trends of pulmonary TB and HIV comorbidity and treatment outcomes according to HIV during the period 2006 to 2014 in the Mexican Institute of Social Security. Analyzed data from this registry including pulmonary tuberculosis patients aged 15 years and older who had been diagnosed during the years 2006 to 2014 in the Mexican Institute of Social Security. The outcomes that we use were incidents rate, failure to treatment and death. Regression models were used to quantify associations between pulmonary tuberculosis and HIV mortality. During the study period, 31,352 patients were registered with pulmonary tuberculosis. The incidence rate observed during 2014 was 11.6 case of PTB per 100,000. The incidence rate for PTB and HIV was 0.345 per 100,000. The PTB incidence rate decreased by 0.07%, differences found in the PTB incidence rate by sex since in women decreased by 5.52% and in man increase by 3.62%. The pulmonary TB with HIV incidence rate decreased by 16.3% during the study period (In women increase 4.81% and in man decrease 21.6%). Analysis of PTB associated with HIV by age groups revealed that the highest incidence rates were observed for the 30 to 44 years old group. Meanwhile, the highest incidence rates of PTB without HIV occurred among the 60 and more years old individuals. We did not find statistically significant differences between treatment failure and PTB patients with HIV and without HIV. The treatment failure was associated with sex and the region of the patient. We found a strong association between HIV and the probability of dying during treatment. Our data suggested that patients suffering from both conditions (PTB and HIV) have no difference in the probability of failure of treatment contrary to other reports. Hypotheses to this is adherence to tuberculosis treatment with people living with HIV/AIDS, detection of PTB

  1. Using an improved phagocytosis assay to evaluate the effect of HIV on specific antibodies to pregnancy-associated malaria.

    Science.gov (United States)

    Ataíde, Ricardo; Hasang, Wina; Wilson, Danny W; Beeson, James G; Mwapasa, Victor; Molyneux, Malcolm E; Meshnick, Steven R; Rogerson, Stephen J

    2010-05-25

    Pregnant women residing in malaria endemic areas are highly susceptible to Plasmodium falciparum malaria, particularly during their first pregnancy, resulting in low birth weight babies and maternal anaemia. This susceptibility is associated with placental sequestration of parasitised red blood cells expressing pregnancy-specific variant surface antigens. Acquisition of antibodies against these variant surface antigens may protect women and their offspring. Functions of such antibodies may include prevention of placental sequestration or opsonisation of parasitised cells for phagocytic clearance. Here we report the development and optimisation of a new high-throughput flow cytometry-based phagocytosis assay using undifferentiated Thp-1 cells to quantitate the amount of opsonizing antibody in patient sera, and apply this assay to measure the impact of HIV on the levels of antibodies to a pregnancy malaria-associated parasite line in a cohort of Malawian primigravid women. The assay showed high reproducibility, with inter-experimental correlation of r(2) = 0.99. In primigravid women, concurrent malaria infection was associated with significantly increased antibodies, whereas HIV decreased the ability to acquire opsonising antibodies (Mann-Whitney ranksum: p = 0.013). This decrease was correlated with HIV-induced immunosuppression, with women with less than 350 x 10(6) CD4+ T- cells/L having less opsonising antibodies (coef: -11.95,P = 0.002). Levels of antibodies were not associated with protection from low birth weight or anaemia. This flow cytometry-based phagocytosis assay proved to be efficient and accurate for the measurement of Fc-receptor mediated phagocytosis-inducing antibodies in large cohorts. HIV was found to affect mainly the acquisition of antibodies to pregnancy-specific malaria in primigravidae. Further studies of the relationship between opsonising antibodies to malaria in pregnancy and HIV are indicated.

  2. HIV-1 RNAs are Not Part of the Argonaute 2 Associated RNA Interference Pathway in Macrophages.

    Directory of Open Access Journals (Sweden)

    Valentina Vongrad

    Full Text Available MiRNAs and other small noncoding RNAs (sncRNAs are key players in post-transcriptional gene regulation. HIV-1 derived small noncoding RNAs (sncRNAs have been described in HIV-1 infected cells, but their biological functions still remain to be elucidated. Here, we approached the question whether viral sncRNAs may play a role in the RNA interference (RNAi pathway or whether viral mRNAs are targeted by cellular miRNAs in human monocyte derived macrophages (MDM.The incorporation of viral sncRNAs and/or their target RNAs into RNA-induced silencing complex was investigated using photoactivatable ribonucleoside-induced cross-linking and immunoprecipitation (PAR-CLIP as well as high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP, which capture Argonaute2-bound miRNAs and their target RNAs. HIV-1 infected monocyte-derived macrophages (MDM were chosen as target cells, as they have previously been shown to express HIV-1 sncRNAs. In addition, we applied small RNA deep sequencing to study differential cellular miRNA expression in HIV-1 infected versus non-infected MDMs.PAR-CLIP and HITS-CLIP data demonstrated the absence of HIV-1 RNAs in Ago2-RISC, although the presence of a multitude of HIV-1 sncRNAs in HIV-1 infected MDMs was confirmed by small RNA sequencing. Small RNA sequencing revealed that 1.4% of all sncRNAs were of HIV-1 origin. However, neither HIV-1 derived sncRNAs nor putative HIV-1 target sequences incorporated into Ago2-RISC were identified suggesting that HIV-1 sncRNAs are not involved in the canonical RNAi pathway nor is HIV-1 targeted by this pathway in HIV-1 infected macrophages.

  3. Cognitive factors associated with the willingness for HIV testing among pregnant women in China.

    Science.gov (United States)

    Li, Chunrong; Yang, Liu; Kong, Jinwang

    2014-01-01

    The spread of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic in the worldwide trend is not contained effectively. The pregnant women infected HIV seriously in the high HIV epidemic areas in China. The transmission of HIV to child may be cut off if HIV positive mother was found early by HIV testing. Pregnant women mandatorily received the HIV counseling and testing services. Most of them did not know the knowledge about HIV prevention and were not willing to receive HIV testing actively. Willingness for HIV testing among pregnant women was investigated, which can help to promote them to take up HIV testing actively. This study assessed the prevalence of the willingness for HIV testing and cognitive factors associated with it. A cross-sectional survey was conducted to 500 pregnant women via face-to-face interviews with anonymous structured questionnaire guided by the Health Belief Model (HBM). The prevalence of the willingness for HIV testing was 58.60%. Perceived higher susceptibility to HIV (multivariate-adjusted odds ratio (ORm) = 2.02, 95% confidence interval (CI): 1.40-5.06), more knowledge for HIV (ORm = 1.92, 95% CI: 1.11-3.87) and perceived less social stigma (ORm = 0.80, 95% CI: 0.34-0.91) were associated with higher willingness for HIV testing among pregnant women. To prevent HIV mother to children transmission, it is necessary to enhance knowledge for HIV, change cognitive factors and increase willingness for HIV testing among pregnant women.

  4. Prevalence and associated factors of late HIV diagnosis in north ...

    African Journals Online (AJOL)

    User

    Moreover, there is still a lack of studies addressing the risk factors ..... Jiang, H., Yin, J., Fan, Y., Liu, J., Zhang, Z, Liu, L. & Nie, S. (2015) Gender difference in advanced HIV disease ... Incidence of HIV-associated tuberculosis among individuals taking combination antiretroviral therapy: a systematic review and meta-analysis.

  5. Cocaine use may modify HIV/ART-associated myocardial steatosis and hepatic steatosis.

    Science.gov (United States)

    Lai, Shenghan; Gerstenblith, Gary; Moore, Richard D; Celentano, David D; Bluemke, David A; Treisman, Glenn; Liu, Chia-Ying; Li, Ji; Chen, Shaoguang; Kickler, Thomas; Lai, Hong

    2017-08-01

    It has been recognized that myocardial and hepatic steatosis may be more prevalent in HIV-infected individuals on antiretroviral therapy (ART); however, factors associated with these conditions have not been thoroughly investigated. The goals of this study were (1) to identify the risk factors for myocardial and hepatic steatosis in HIV-infected African Americans (AAs) and explore whether ART use is independently associated with myocardial and hepatic steatosis, and (2) to examine whether and how cocaine use influences any associations of ART use with myocardial and hepatic steatosis. Between June 2010 and December 2013, 220 HIV-infected AAs in Baltimore, Maryland, were enrolled in a study investigating HIV/ART-associated myocardial and hepatic damage. Proton magnetic resonance spectroscopy was performed to quantify myocardial and hepatic triglyceride contents. Sociodemographic, medical and laboratory data were also obtained. Robust regression model was employed to perform primary statistical analysis. Robust regression analyses showed that (1) duration of protease inhibitor (PI) use was independently associated with myocardial and hepatic triglyceride contents, (2) duration of PI use was independently associated with myocardial triglyceride in cocaine users (p=0.025), but not in cocaine never-users (p=0.84), and (3) duration of PI use was independently associated with hepatic triglyceride in cocaine users, but not in cocaine never-users (p=0.52). Cocaine use may trigger/exacerbate the toxicity of PI in ART-associated myocardial and hepatic steatosis, suggesting that cocaine abstinence/reduced use may retard these ART-associated comorbidities. Clinical trials should be conducted to examine whether reduced cocaine use improves HIV/AIDS-associated myocardial and hepatic steatosis. Copyright © 2017. Published by Elsevier B.V.

  6. HIV-1 Infection of Primary CD4+ T Cells Regulates the Expression of Specific Human Endogenous Retrovirus HERV-K (HML-2) Elements.

    Science.gov (United States)

    Young, George R; Terry, Sandra N; Manganaro, Lara; Cuesta-Dominguez, Alvaro; Deikus, Gintaras; Bernal-Rubio, Dabeiba; Campisi, Laura; Fernandez-Sesma, Ana; Sebra, Robert; Simon, Viviana; Mulder, Lubbertus C F

    2018-01-01

    Endogenous retroviruses (ERVs) occupy extensive regions of the human genome. Although many of these retroviral elements have lost their ability to replicate, those whose insertion took place more recently, such as the HML-2 group of HERV-K elements, still retain intact open reading frames and the capacity to produce certain viral RNA and/or proteins. Transcription of these ERVs is, however, tightly regulated by dedicated epigenetic control mechanisms. Nonetheless, it has been reported that some pathological states, such as viral infections and certain cancers, coincide with ERV expression, suggesting that transcriptional reawakening is possible. HML-2 elements are reportedly induced during HIV-1 infection, but the conserved nature of these elements has, until recently, rendered their expression profiling problematic. Here, we provide comprehensive HERV-K HML-2 expression profiles specific for productively HIV-1-infected primary human CD4 + T cells. We combined enrichment of HIV-1 infected cells using a reporter virus expressing a surface reporter for gentle and efficient purification with long-read single-molecule real-time sequencing. We show that three HML-2 proviruses-6q25.1, 8q24.3, and 19q13.42-are upregulated on average between 3- and 5-fold in HIV-1-infected CD4 + T cells. One provirus, HML-2 12q24.33, in contrast, was repressed in the presence of active HIV replication. In conclusion, this report identifies the HERV-K HML-2 loci whose expression profiles differ upon HIV-1 infection in primary human CD4 + T cells. These data will help pave the way for further studies on the influence of endogenous retroviruses on HIV-1 replication. IMPORTANCE Endogenous retroviruses inhabit big portions of our genome. Moreover, although they are mainly inert, some of the evolutionarily younger members maintain the ability to express both RNA and proteins. We have developed an approach using long-read single-molecule real-time (SMRT) sequencing that produces long reads that

  7. A cohort pilot study on HIV-associated neuropsychological impairments in haemophilia patients

    Directory of Open Access Journals (Sweden)

    Silvia eRiva

    2015-06-01

    Full Text Available Despite advances in the management of HIV infection with the introduction of combination antiretroviral therapy (cART, it is well known that HIV can directly infect the central nervous system (CNS and, as a result of such infection, neuropsychological impairments can be manifested. In this study we tried to determine whether seropositivity was associated with a poor neuropsychological performance in patients with hemophilia and HIV. Such a cohort of patients is very often underrepresented and understudied in the HIV literature. To amend such a gap, we carried out an extensive neuropsychological evaluation on these patients, and compared their performance with that of a group of seronegative hemophilia patients. The results revealed that HIV infection in HIV seropositive (HIV+ hemophilia patients was associated with deficits in attention, short-term memory, abstraction and visual recognition. Such results are still preliminary and explorative due to the small cohort of patients enrolled. However, the results do seem to have some important implications for day-to-day functioning, as the level of impairment detected may cause difficulties in completing common everyday tasks such as maintaining adherence to complex medication regimens, or maintaining social life activities. Continued research into the mechanisms related to HIV and neurocognitive dysfunction may provide targets for interventions that could have meaningful consequences in the real world for HIV hemophilia patients.

  8. Proteinuria is associated with neurocognitive impairment in antiretroviral therapy treated HIV-infected individuals.

    Science.gov (United States)

    Kalayjian, Robert C; Wu, Kunling; Evans, Scott; Clifford, David B; Pallaki, Muraldihar; Currier, Judith S; Smryzynski, Marlene

    2014-09-01

    Proteinuria is a marker of vascular dysfunction that predicted increased cardiovascular mortality and is associated with neurocognitive impairment (NCI) in population-based studies. We examined associations between proteinuria and HIV-associated NCI. Multivariable logistic regression was used to examine associations between NCI at the first neurocognitive assessment (baseline) and simultaneous, clinically significant proteinuria [as random spot urine protein-to-creatinine ratios (UP/Cr) ≥200 mg/g] in a prospective multicenter observational cohort study. Generalized estimating equations were used to examine associations between baseline proteinuria and subsequent NCI among subjects without NCI at baseline. NCI was defined as a Z-score, derived from the combination of normalized scores from the Trailmaking A and B and the Wechsler Adult Intelligence Scale-Revised Digit Symbol tests. A total of 1972 subjects were included in this analysis. Baseline proteinuria was associated with increased odds of NCI [odds ratio (OR): 1.41, 95% confidence interval (CI): 1.08 to 1.85; P = 0.01] and with subsequent NCI among subjects without NCI at baseline (OR: 1.39, 95% CI: 1.01 to 1.93; P = 0.046) in multivariable models adjusted for risk factors and potential confounders. Similar associations were evident when these analyses were limited to visits at which time study subjects maintained plasma HIV RNA levels <200 copies per milliliter. The association between proteinuria and NCI observed in this study adds to a growing body of evidence implicating contributions by vascular disease to NCI in antiretroviral treated individuals. Studies examining interventions that improve vascular function are warranted.

  9. A gene expression signature associated with survival in metastatic melanoma

    Science.gov (United States)

    Mandruzzato, Susanna; Callegaro, Andrea; Turcatel, Gianluca; Francescato, Samuela; Montesco, Maria C; Chiarion-Sileni, Vanna; Mocellin, Simone; Rossi, Carlo R; Bicciato, Silvio; Wang, Ena; Marincola, Francesco M; Zanovello, Paola

    2006-01-01

    Background Current clinical and histopathological criteria used to define the prognosis of melanoma patients are inadequate for accurate prediction of clinical outcome. We investigated whether genome screening by means of high-throughput gene microarray might provide clinically useful information on patient survival. Methods Forty-three tumor tissues from 38 patients with stage III and stage IV melanoma were profiled with a 17,500 element cDNA microarray. Expression data were analyzed using significance analysis of microarrays (SAM) to identify genes associated with patient survival, and supervised principal components (SPC) to determine survival prediction. Results SAM analysis revealed a set of 80 probes, corresponding to 70 genes, associated with survival, i.e. 45 probes characterizing longer and 35 shorter survival times, respectively. These transcripts were included in a survival prediction model designed using SPC and cross-validation which allowed identifying 30 predicting probes out of the 80 associated with survival. Conclusion The longer-survival group of genes included those expressed in immune cells, both innate and acquired, confirming the interplay between immunological mechanisms and the natural history of melanoma. Genes linked to immune cells were totally lacking in the poor-survival group, which was instead associated with a number of genes related to highly proliferative and invasive tumor cells. PMID:17129373

  10. A gene expression signature associated with survival in metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Rossi Carlo R

    2006-11-01

    Full Text Available Abstract Background Current clinical and histopathological criteria used to define the prognosis of melanoma patients are inadequate for accurate prediction of clinical outcome. We investigated whether genome screening by means of high-throughput gene microarray might provide clinically useful information on patient survival. Methods Forty-three tumor tissues from 38 patients with stage III and stage IV melanoma were profiled with a 17,500 element cDNA microarray. Expression data were analyzed using significance analysis of microarrays (SAM to identify genes associated with patient survival, and supervised principal components (SPC to determine survival prediction. Results SAM analysis revealed a set of 80 probes, corresponding to 70 genes, associated with survival, i.e. 45 probes characterizing longer and 35 shorter survival times, respectively. These transcripts were included in a survival prediction model designed using SPC and cross-validation which allowed identifying 30 predicting probes out of the 80 associated with survival. Conclusion The longer-survival group of genes included those expressed in immune cells, both innate and acquired, confirming the interplay between immunological mechanisms and the natural history of melanoma. Genes linked to immune cells were totally lacking in the poor-survival group, which was instead associated with a number of genes related to highly proliferative and invasive tumor cells.

  11. Intra- and interspecies gene expression models for predicting drug response in canine osteosarcoma.

    Science.gov (United States)

    Fowles, Jared S; Brown, Kristen C; Hess, Ann M; Duval, Dawn L; Gustafson, Daniel L

    2016-02-19

    Genomics-based predictors of drug response have the potential to improve outcomes associated with cancer therapy. Osteosarcoma (OS), the most common primary bone cancer in dogs, is commonly treated with adjuvant doxorubicin or carboplatin following amputation of the affected limb. We evaluated the use of gene-expression based models built in an intra- or interspecies manner to predict chemosensitivity and treatment outcome in canine OS. Models were built and evaluated using microarray gene expression and drug sensitivity data from human and canine cancer cell lines, and canine OS tumor datasets. The "COXEN" method was utilized to filter gene signatures between human and dog datasets based on strong co-expression patterns. Models were built using linear discriminant analysis via the misclassification penalized posterior algorithm. The best doxorubicin model involved genes identified in human lines that were co-expressed and trained on canine OS tumor data, which accurately predicted clinical outcome in 73 % of dogs (p = 0.0262, binomial). The best carboplatin model utilized canine lines for gene identification and model training, with canine OS tumor data for co-expression. Dogs whose treatment matched our predictions had significantly better clinical outcomes than those that didn't (p = 0.0006, Log Rank), and this predictor significantly associated with longer disease free intervals in a Cox multivariate analysis (hazard ratio = 0.3102, p = 0.0124). Our data show that intra- and interspecies gene expression models can successfully predict response in canine OS, which may improve outcome in dogs and serve as pre-clinical validation for similar methods in human cancer research.

  12. Association between oral candidiasis and low CD4+ count among HIV positive patients in Hoima Regional Referral Hospital.

    Science.gov (United States)

    Nanteza, Martina; Tusiime, Jayne B; Kalyango, Joan; Kasangaki, Arabat

    2014-11-28

    The aim of this study was to determine the prevalence of Human Immune Virus (HIV) related oral lesions and their association with Cluster of Differentiation 4 (CD4+) count among treatment naïve HIV positive patients. This was a descriptive and analytical cross sectional study. Participants were 346 treatment naïve HIV positive adult patients. These were consecutively recruited from Hoima Regional Referral hospital between March and April 2012. Data collection involved interviews, oral examinations and laboratory analysis. A total of 168(48.6%) participants had oral lesions. The four commonest lesions were oral candidiasis (24.9%, CI = 20.6-29.7%), melanotic hyperpigmentation (17.3%, CI = 13.7-21.7%), kaposi sarcoma (9.3%, CI = 6.6-12.8%) and Oral Hairy Leukoplakia (OHL) (5.5%, CI = 3.5-8.4%). There was significant association between oral candidiasis and immunosuppression measured as CD4+ less than 350 cells/mm3 (OR = 2.69, CI = 1.608-4.502, p Oral candidiasis was the only oral lesion significantly predictive of immunosuppression (OR = 2.56, CI = 1.52-4.30, p Oral candidiasis can be considered as a marker for immunesuppression, making routine oral examinations essential in the management of HIV positive patients.

  13. Spontaneous control of HIV-1 viremia in a subject with protective HLA-B plus HLA-C alleles and HLA-C associated single nucleotide polymorphisms.

    Science.gov (United States)

    Moroni, Marco; Ghezzi, Silvia; Baroli, Paolo; Heltai, Silvia; De Battista, Davide; Pensieroso, Simone; Cavarelli, Mariangela; Dispinseri, Stefania; Vanni, Irene; Pastori, Claudia; Zerbi, Pietro; Tosoni, Antonella; Vicenzi, Elisa; Nebuloni, Manuela; Wong, Kim; Zhao, Hong; McHugh, Sarah; Poli, Guido; Lopalco, Lucia; Scarlatti, Gabriella; Biassoni, Roberto; Mullins, James I; Malnati, Mauro S; Alfano, Massimo

    2014-12-05

    Understanding the mechanisms by which some individuals are able to naturally control HIV-1 infection is an important goal of AIDS research. We here describe the case of an HIV-1(+) woman, CASE1, who has spontaneously controlled her viremia for the last 14 of her 20 years of infection. CASE1 has been clinically monitored since 1993. Detailed immunological, virological and histological analyses were performed on samples obtained between 2009 and 2011. As for other Elite Controllers, CASE1 is characterized by low to undetectable levels of plasma HIV-1 RNA, peripheral blood mononuclear cell (PBMC) associated HIV-1 DNA and reduced in vitro susceptibility of target cells to HIV-1 infection. Furthermore, a slow rate of virus evolution was demonstrated in spite the lack of assumption of any antiretroviral agent. CASE1 failed to transmit HIV-1 to either her sexual male partner or to her child born by vaginal delivery. Normal values and ratios of T and B cells were observed, along with normal histology of the intestinal mucosa. Attempts to isolate HIV-1 from her PBMC and gut-derived cells were unsuccessful, despite expression of normal cell surface levels of CD4, CCRC5 and CXCR4. CASE1 did not produce detectable anti-HIV neutralizing antibodies in her serum or genital mucosal fluid although she displayed potent T cell responses against HIV-1 Gag and Nef. CASE1 also possessed multiple genetic polymorphisms, including HLA alleles (B*14, B*57, C*06 and C*08.02) and HLA-C single nucleotide polymorphisms (SNPs, rs9264942 C/C and rs67384697 del/del), that have been previously individually associated with spontaneous control of plasma viremia, maintenance of high CD4(+) T cell counts and delayed disease progression. CASE1 has controlled her HIV-1 viremia below the limit of detection in the absence of antiretroviral therapy for more than 14 years and has not shown any sign of immunologic deterioration or disease progression. Co-expression of multiple protective HLA alleles, HLA

  14. Monocyte activation in HIV/HCV coinfection correlates with cognitive impairment.

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    Hans Rempel

    Full Text Available Coinfection with human immunodeficiency virus (HIV and hepatitis C virus (HCV challenges the immune system with two viruses that elicit distinct immune responses. Chronic immune activation is a hallmark of HIV infection and an accurate indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART effectively prolongs life and significantly improves immune function. HIV/HCV coinfected individuals have peripheral immune activation despite effective ART control of HIV viral load. Here we examined freshly isolated CD14 monocytes for gene expression using high-density cDNA microarrays and analyzed T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV and HIV, and HIV-suppressed coinfected subjects. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological performance, which were summarized as a global deficit score (GDS. Monocyte gene expression analysis in HIV-suppressed coinfected subjects identified 43 genes that were elevated greater than 2.5 fold. Correlative analysis of subjects' GDS and gene expression found eight genes with significance after adjusting for multiple comparisons. Correlative expression of six genes was confirmed by qPCR, five of which were categorized as type 1 IFN response genes. Global deficit scores were not related to plasma lipopolysaccharide levels. In the T cell compartment, coinfection significantly increased expression of activation markers CD38 and HLADR on both CD4 and CD8 T cells but did not correlate with GDS. These findings indicate that coinfection is associated with a type 1 IFN monocyte activation profile which was further found to correlate with cognitive impairment, even in subjects with controlled HIV infection. HIV-suppressed coinfected subjects with controlled HIV viral load experiencing immune activation could benefit significantly from successful anti-HCV therapy and may be

  15. Medroxyprogesterone acetate-treated human, primary endometrial epithelial cells reveal unique gene expression signature linked to innate immunity and HIV-1 susceptibility.

    Science.gov (United States)

    Woods, Matthew W; Zahoor, Muhammad Atif; Dizzell, Sara; Verschoor, Chris P; Kaushic, Charu

    2018-01-01

    Medroxyprogesterone acetate (MPA), a progestin-based hormonal contraceptive designed to mimic progesterone, has been linked to increased human immunodeficiency virus (HIV-1) susceptibility. Genital epithelial cells (GECs) form the mucosal lining of the female genital tract (FGT) and provide the first line of protection against HIV-1. The impact of endogenous sex hormones or MPA on the gene expression profile of GECs has not been comprehensively documented. Using microarray analysis, we characterized the transcriptional profile of primary endometrial epithelial cells grown in physiological levels of E2, P4, and MPA. Each hormone treatment altered the gene expression profile of GECs in a unique manner. Interestingly, although MPA is a progestogen, the gene expression profile induced by it was distinct from P4. MPA increased gene expression of genes related to inflammation and cholesterol synthesis linked to innate immunity and HIV-1 susceptibility. The analysis of gene expression profiles provides insights into the effects of sex hormones and MPA on GECs and allows us to posit possible mechanisms of the MPA-mediated increase in HIV-1 acquisition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. HIV disclosure and stigma among women living with HIV in Denmark

    DEFF Research Database (Denmark)

    Wessman, Maria; Thorsteinsson, Kristina; Storgaard, Merete

    2017-01-01

    OBJECTIVE: To identify disclosure, stigma and predictors of non-disclosure among women living with HIV in Denmark. METHODS: A questionnaire study of women living with HIV in Denmark was performed. The enrolment period was from February 2013 to March 2014. Logistic regression was used to estimate......%), friends (63%) and children (41%). The primary reason for non-disclosure was a feeling that it did not concern others (55%), although reactions upon disclosure were mainly positive in 53%. Predictors of non-disclosure were being of black or Asian ethnicity. Following their HIV diagnosis, 40% no longer...... diagnosis to fewer than three people and black or Asian ethnicity predicted non-disclosure. HIV-related stigma regarding sex and contact with others is still highly prevalent; however, reactions to disclosure were mainly positive and associated with secondary positive gains. We strongly urge healthcare...

  17. Genome-wide association scan in HIV-1-infected individuals identifying variants influencing disease course.

    Directory of Open Access Journals (Sweden)

    Daniëlle van Manen

    Full Text Available BACKGROUND: AIDS develops typically after 7-11 years of untreated HIV-1 infection, with extremes of very rapid disease progression (15 years. To reveal additional host genetic factors that may impact on the clinical course of HIV-1 infection, we designed a genome-wide association study (GWAS in 404 participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. METHODS: The association of SNP genotypes with the clinical course of HIV-1 infection was tested in Cox regression survival analyses using AIDS-diagnosis and AIDS-related death as endpoints. RESULTS: Multiple, not previously identified SNPs, were identified to be strongly associated with disease progression after HIV-1 infection, albeit not genome-wide significant. However, three independent SNPs in the top ten associations between SNP genotypes and time between seroconversion and AIDS-diagnosis, and one from the top ten associations between SNP genotypes and time between seroconversion and AIDS-related death, had P-values smaller than 0.05 in the French Genomics of Resistance to Immunodeficiency Virus cohort on disease progression. CONCLUSIONS: Our study emphasizes that the use of different phenotypes in GWAS may be useful to unravel the full spectrum of host genetic factors that may be associated with the clinical course of HIV-1 infection.

  18. Genome-Wide Association Scan in HIV-1-Infected Individuals Identifying Variants Influencing Disease Course

    Science.gov (United States)

    van Manen, Daniëlle; Delaneau, Olivier; Kootstra, Neeltje A.; Boeser-Nunnink, Brigitte D.; Limou, Sophie; Bol, Sebastiaan M.; Burger, Judith A.; Zwinderman, Aeilko H.; Moerland, Perry D.; van 't Slot, Ruben; Zagury, Jean-François; van 't Wout, Angélique B.; Schuitemaker, Hanneke

    2011-01-01

    Background AIDS develops typically after 7–11 years of untreated HIV-1 infection, with extremes of very rapid disease progression (15 years). To reveal additional host genetic factors that may impact on the clinical course of HIV-1 infection, we designed a genome-wide association study (GWAS) in 404 participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. Methods The association of SNP genotypes with the clinical course of HIV-1 infection was tested in Cox regression survival analyses using AIDS-diagnosis and AIDS-related death as endpoints. Results Multiple, not previously identified SNPs, were identified to be strongly associated with disease progression after HIV-1 infection, albeit not genome-wide significant. However, three independent SNPs in the top ten associations between SNP genotypes and time between seroconversion and AIDS-diagnosis, and one from the top ten associations between SNP genotypes and time between seroconversion and AIDS-related death, had P-values smaller than 0.05 in the French Genomics of Resistance to Immunodeficiency Virus cohort on disease progression. Conclusions Our study emphasizes that the use of different phenotypes in GWAS may be useful to unravel the full spectrum of host genetic factors that may be associated with the clinical course of HIV-1 infection. PMID:21811574

  19. KSHV/HHV-8 associated lymph node based lymphomas in HIV seronegative subjects. Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Quyen Nguyen, MD

    2016-12-01

    Full Text Available Extracavitary primary effusion lymphoma (ExPEL is a rare, high-grade lymphoproliferative disorder that displays immunoblastic, plasmablastic, or anaplastic morphology. It usually lacks expression of B-cell and T-cell markers, but often expresses the plasma cell markers CD138 and MUM1, and the activation marker CD30, along with EMA. ExPEL, similar to classic PEL occurring as lymphomatous effusions in serous body cavities without an associated tumor mass, is consistently associated with human herpes virus-8 (HHV8 infection, while a majority of cases also exhibits Epstein–Barr virus (EBV co-infection. Clinically, it is characterized by an almost exclusive male predominance (98% male, HIV-positivity (96% of patients are HIV+, acute presentation with B symptoms, and unfavorable overall survival (40% of patients die within 2 months. We report an asymptomatic HIV-negative female patient with incidentally found splenomegaly and extensive PET FDG-avid retroperitoneal, pelvic, and mediastinal lymphadenopathy. A core biopsy of her right pelvic lymph node showed aggregates of atypical cells with anaplastic features. Immunohistochemistry revealed that the neoplastic cells were positive for CD45, CD20, CD30, MUM1, CD138, EMA, CD3, HHV-8 and EBER. The diagnosis of ExPEL was established. Against medical advice and given the absence of significant symptoms, the patient refused to start treatment. Four months after the diagnosis, the patient remains asymptomatic, and follow-up CT scan demonstrates stability of her lymphadenopathy. We present here a case of ExPEL in which the patient's presentation defies the clinical norms, illustrating that ExPEL should also be included in the differential diagnosis of lymphomas occurring in asymptomatic HIV-negative patients.

  20. A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV.

    Science.gov (United States)

    Triplette, Matthew; Attia, Engi F; Akgün, Kathleen M; Soo Hoo, Guy W; Freiberg, Matthew S; Butt, Adeel A; Wongtrakool, Cherry; Goetz, Matthew Bidwell; Brown, Sheldon T; Graber, Christopher J; Huang, Laurence; Crothers, Kristina

    2017-01-01

    The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects. We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonary function markers of COPD. Mild or greater emphysema (>10% lung involvement) was present in 31% of subjects. Low CD4/CD8 ratio was associated with >10% emphysema in multivariable models, adjusting for risk factors including smoking, current and nadir CD4 count and HIV RNA level. Those with CD4/CD8 ratio 10% emphysema compared to those with a ratio >1.0 in fully adjusted models. A low CD4/CD8 ratio was also associated with reduced diffusion capacity (DLCO). A low CD4/CD8 ratio was associated with emphysema and low DLCO in HIV+ subjects, independent of other risk factors and clinical markers of HIV. The CD4/CD8 ratio may be a useful, clinically available, marker for risk of emphysema in HIV+ subjects in the antiretroviral therapy (ART) era.

  1. Observed versus predicted cardiovascular events and all-cause death in HIV infection: a longitudinal cohort study.

    Science.gov (United States)

    De Socio, Giuseppe Vittorio; Pucci, Giacomo; Baldelli, Franco; Schillaci, Giuseppe

    2017-06-12

    The aim of the study was to assess the applicability of an algorithm predicting 10-year cardiovascular disease (CVD) generated in the setting of the Framingham Heart Study to a real-life, contemporary Italian cohort of HIV-positive subjects. The study was an observational longitudinal cohort study. The probability for 10-year CVD events according to the Framingham algorithm was assessed in 369 consecutive HIV-positive participants free from overt CVD enrolled in 2004, who were followed for a median of 10.0 years (interquartile range, 9.1-10.1). Cardiovascular events included myocardial infarction, hospitalized heart failure, revascularized angina, sudden cardiac death, stroke, peripheral arterial disease. Over 3097 person-years of observation, we observed a total of 34 CVD events, whereas Framingham algorithm predicted the occurrence of 34.3 CVD events. CVD event rate was 11.0/1000 person-years of follow-up. In a receiver operating characteristics curve analysis, Framingham risk equation showed an excellent predictive value for incident CVD events (c-statistics, 0.83; 95% confidence interval, 0.76-0.90). In a multivariable Cox analysis, age, smoking and diabetes were independent predictors of CVD events. All-cause death rate was 20.0/1000 person-years of follow-up (n = 62 deaths). Causes of death included liver diseases (18), malignancies (14), AIDS-related (11); cardiovascular (9) and others (10). In a Cox analysis, age, AIDS diagnosis and chronic hepatitis were independent predictors of death. Observed CVD events in HIV-infected patients were well predicted by Framingham algorithm. Established major CVD risk factors are the strongest determinants of CVD morbidity in an Italian contemporary cohort of HIV-positive subjects. Interventions to modify traditional risk factors are urgently needed in HIV people.

  2. Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses

    Science.gov (United States)

    Mitra, Sanjana; Chen, Shiyi; Gogolishvili, David; Globerman, Jason; Chambers, Lori; Wilson, Mike; Logie, Carmen H; Shi, Qiyun; Morassaei, Sara; Rourke, Sean B

    2016-01-01

    Objective To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV. Data sources A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health-related outcomes published between 1996 and 2013. Study eligibility criteria Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion. Outcome measures Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours. Results 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV. Conclusions This systematic review and series of meta-analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to

  3. Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses.

    Science.gov (United States)

    Rueda, Sergio; Mitra, Sanjana; Chen, Shiyi; Gogolishvili, David; Globerman, Jason; Chambers, Lori; Wilson, Mike; Logie, Carmen H; Shi, Qiyun; Morassaei, Sara; Rourke, Sean B

    2016-07-13

    To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV. A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health-related outcomes published between 1996 and 2013. Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion. Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours. 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV. This systematic review and series of meta-analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to reduce the impact of HIV-related stigma on the health and well-being of people living

  4. HIV prevalence and factors associated with HIV infection among transgender women in Cambodia: results from a national Integrated Biological and Behavioral Survey.

    Science.gov (United States)

    Chhim, Srean; Ngin, Chanrith; Chhoun, Pheak; Tuot, Sovannary; Ly, Cheaty; Mun, Phalkun; Pal, Khondyla; Macom, John; Dousset, Jean-Philippe; Mburu, Gitau; Yi, Siyan

    2017-08-11

    To examine factors associated with HIV infection among transgender women in Cambodia. Cross-sectional study. HIV high-burden sites including the capital city and 12 provinces. This study included 1375 sexually active transgender women with a mean age of 25.9 years (SD 7.1), recruited by using respondent-driven sampling for structured questionnaire interviews and rapid finger-prick HIV testing. HIV infection detected by using Determine antibody test. HIV prevalence among this population was 5.9%. After adjustment for other covariates, participants living in urban areas were twice as likely to be HIV infected as those living in rural areas. Participants with primary education were 1.7 times as likely to be infected compared with those with high school education. HIV infection increased with age; compared with those aged 18-24 years, the odds of being HIV infected were twice as high among transgender women aged 25-34 years and 2.8 times higher among those aged ≥35 years. Self-injection of gender affirming hormones was associated with a fourfold increase in the odds of HIV infection. A history of genital sores over the previous 12 months increased the odds of HIV infection by threefold. Transgender women with stronger feminine identity, dressing as a woman all the time, were twice as likely to be HIV infected compared with those who did not dress as a woman all the time. Having never used online services developed for transgender women in the past six months was also associated with higher odds of being HIV infected. Transgender women in Cambodia are at high risk of HIV. To achieve the goal of eliminating HIV in Cambodia, effective combination prevention strategies addressing the above risk factors among transgender women should be strengthened. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Mucosal immunity in HIV infection: what can be done to restore gastrointestinal-associated lymphoid tissue function?

    Science.gov (United States)

    George, Michael D; Asmuth, David M

    2014-06-01

    This review describes the impact of HIV infection on gut-associated lymphoid tissue, the mechanisms for persistent gut-associated lymphoid tissue dysfunction despite effective antiretroviral therapy, and potential strategies to restore gut-associated lymphoid tissue function and promote immune reconstitution. Recent studies indicate that unresolved microbial translocation and intestinal dysbiosis may continue to promote enteropathy as well as HIV-associated and non-HIV-associated conditions in many HIV patients who otherwise maintain therapeutic control of systemic viral replication. Several novel therapeutic approaches to reduce intestinal inflammation and mitigate microbial translocation may hold promise for restoring gastrointestinal health and thereby increasing the efficacy of immune reconstitution in HIV-infected patients undergoing antiretroviral therapy.

  6. Predictive value of MSH2 gene expression in colorectal cancer treated with capecitabine

    DEFF Research Database (Denmark)

    Jensen, Lars H; Danenberg, Kathleen D; Danenberg, Peter V

    2007-01-01

    was associated with a hazard ratio of 0.5 (95% confidence interval, 0.23-1.11; P = 0.083) in survival analysis. CONCLUSION: The higher gene expression of MSH2 in responders and the trend for predicting overall survival indicates a predictive value of this marker in the treatment of advanced CRC with capecitabine.......PURPOSE: The objective of the present study was to evaluate the gene expression of the DNA mismatch repair gene MSH2 as a predictive marker in advanced colorectal cancer (CRC) treated with first-line capecitabine. PATIENTS AND METHODS: Microdissection of paraffin-embedded tumor tissue, RNA...

  7. Association of depression with social support and self-esteem among HIV positives.

    Science.gov (United States)

    Jagannath, Vinita; Unnikrishnan, B; Hegde, Supriya; Ramapuram, John T; Rao, S; Achappa, B; Madi, D; Kotian, M S

    2011-12-01

    Depression in Human Immunodeficiency Virus (HIV) positives has implications such as poor drug compliance, lower quality of life, faster progression to full blown Acquired Immunodeficiency Syndrome (AIDS) and higher mortality. To assess depression, social support and self-esteem in HIV positives and to find out the association of depression with social support and self-esteem among HIV positive patients. Kasturba Medical College (KMC) Hospital, a tertiary care hospital, Mangalore, India and cross-sectional design. Study constituted of 105 HIV positive subjects; depression was assessed using BDI (Beck depression inventory), social support was assessed using Lubben social network scale and self-esteem was assessed using Rosenberg self-esteem scale. Kappa statistics was used to measure the agreement of depression assessed by BDI with clinical diagnosis of depression. Logistic regression analyses were done to find out predictors of depression among HIV positives. All analyses were conducted using Statistical Package for Social Sciences (SPSS) version 11.5. Depression was found to be present in 43.8% of HIV positives. Among the study subjects, 10.5% had high risk for isolation and low self-esteem was found only among 5.7%. In univariate analysis both gender and self-esteem were significantly associated with depression whereas in multivariate analysis only self-esteem was found to be significantly associated with depression. The present study shows a high prevalence of depression in HIV positive patients along with the importance of self-esteem. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Comparison of HIV DNA and RNA in gut-associated lymphoid tissue of HIV-infected controllers and noncontrollers.

    Science.gov (United States)

    Hatano, Hiroyu; Somsouk, Ma; Sinclair, Elizabeth; Harvill, Kara; Gilman, Lee; Cohen, Michelle; Hoh, Rebecca; Hunt, Peter W; Martin, Jeffrey N; Wong, Joseph K; Deeks, Steven G; Yukl, Steven A

    2013-09-10

    HIV-infected controllers have provided novel insights into mechanisms of viral control. We investigated the degree to which HIV DNA and RNA are present in gut-associated lymphoid tissue (GALT) of controllers. Cross-sectional cohort study. Colorectal biopsy pieces were obtained from five untreated noncontrollers, five ART-suppressed patients, and nine untreated controllers. Rectal HIV DNA was lower in controllers (median 496 copies/10(6) CD4 T cells) than in untreated noncontrollers (117483 copies/10(6) CD4+ T cells, P = 0.001) and ART-suppressed patients (6116 copies/10(6) CD4 T cells, P = 0.004). Similarly, rectal HIV RNA was lower in controllers (19 copies/10(6) CD4 T cells) than in noncontrollers (15210 copies/10(6) CD4+ T cells, P = 0.001) and ART-suppressed patients (1625 copies/10(6) CD4+ T cells, P = 0.0599). Rectal HIV RNA/DNA ratios were not statistically different between the three groups. Despite being able to maintain very low plasma HIV RNA levels in the absence of antiretroviral therapy (ART), HIV-infected controllers have readily measurable levels of HIV DNA and RNA in GALT. As expected, controllers had lower rectal HIV DNA and RNA compared with untreated noncontrollers and ART-suppressed individuals. Compared with the mechanisms of 'natural' viral control of controllers, long-term ART does not reduce the total HIV reservoir to the level of controllers.

  9. Factors Associated with Non-disclosure of HIV Status in a Cohort of Childbearing HIV-Positive Women in Ukraine.

    Science.gov (United States)

    Ahn, Jane V; Bailey, Heather; Malyuta, Ruslan; Volokha, Alla; Thorne, Claire

    2016-01-01

    Ukraine has one of the largest populations of persons living with HIV in Europe. Data on 2019 HIV-positive married or cohabiting women enrolled in a postnatal cohort from 2007 to 2012 were analysed to investigate prevalence and factors associated with self-reported non-disclosure of HIV status. Median age at enrolment was 27.5 years, with two-thirds diagnosed during their most recent pregnancy. Almost all had received antenatal antiretroviral therapy and 24 % were taking it currently. One-tenth (n = 198) had not disclosed their HIV status to their partner and 1 in 20 (n = 93) had disclosed to no-one. Factors associated with non-disclosure were: unmarried status (AOR 2.99 (95 % CI 1.51-5.92), younger age at leaving full-time education (AOR 0.41 (95 % CI 0.19-0.88) for ≥19 years vs ≤16 years) and lack of knowledge of partner's HIV status (AOR 2.01 (95 % CI 1.09-3.66). Further work is needed to support disclosure in some groups and to explore relationships between disclosure and psychological factors in this setting, including depression, lack of support and perception of stigma.

  10. HIV-infected persons with bipolar disorder are less aware of memory deficits than HIV-infected persons without bipolar disorder.

    Science.gov (United States)

    Blackstone, Kaitlin; Tobin, Alexis; Posada, Carolina; Gouaux, Ben; Grant, Igor; Moore, David J; The Hiv Neurobehavioral Research Program Hnrp

    2012-01-01

    Episodic memory deficits are common in HIV infection and bipolar disorder, but patient insight into such deficits remains unclear. Thirty-four HIV-infected individuals without bipolar disorder (HIV+/BD-) and 47 HIV+ individuals with comorbid bipolar disorder (HIV+/BD+) were administered the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised to examine objective learning/memory functioning. Subjective memory complaints were assessed via the memory subscale of the Patient's Assessment of Own Functioning Inventory. HIV+/BD+ individuals performed poorer on tests of visual learning and visual/verbal recall than did HIV+/BD- participants (ps Memory complaints only predicted verbal learning (at a trend level, p = .10) and recall (p = .03) among the HIV+/BD- individuals. Memory complaints were not associated with memory performance within the HIV+/BD+ group (ps > .10). Memory complaints were associated with depressive symptoms in both groups (ps memory abilities was particularly poor among HIV+/BD+ individuals (i.e., objective learning/memory did not correspond to reported complaints), which has important implications for the capacity of these individuals to engage in error-monitoring and compensatory strategies in daily life. Memory complaints are associated with depressed mood regardless of group membership. Among HIV+/BD+ individuals, these complaints may also signify worse HIV disease status and problems with everyday functioning. Clinicians and researchers should be cognizant of what these complaints indicate in order to lead treatment most effectively; use of objective neurocognitive assessments may still be warranted when working with these populations.

  11. Are we meeting the American Diabetes Association goals for HIV-infected patients with diabetes mellitus?

    Science.gov (United States)

    Adeyemi, Oluwatoyin; Vibhakar, Sonia; Max, Blake

    2009-09-01

    We determined rates of achieving the American Diabetes Association goals among human immunodeficiency virus (HIV)-infected diabetic patients. American Diabetes Association goals (for hemoglobin A1c, blood pressure, and lipid levels) were defined by 2008 American Diabetes Association guidelines. HIV-infected diabetic patients achieved American Diabetes Association goals at rates similar to those in general medicine clinic patients. A multidisciplinary approach is needed to improve diabetes management in HIV clinics.

  12. HIV and Syphilis Prevalence and Associated Risks in the Cameroonian Armed Forces.

    Science.gov (United States)

    Grillo, Michael; Tran, Bonnie Robin; Tamoufe, Ubald; Djoko, Cyrille F; Saylors, Karen; Woodland, Kelly; Wangmene, L T C; Macera, Caroline

    2017-01-01

    Continued surveillance of the HIV epidemic is critical to monitor changes in trends and risk behaviors. A 2005 study in the Cameroonian Armed Forces (CAF) found an HIV prevalence of 11.3% among male and female service members. The purpose of the current study is to determine the 5-year change in the HIV prevalence, estimate the prevalence of syphilis, and examine factors associated with infection in the CAF. Participants were male and female service members 18 years of age or older who were stationed at one of the 10 military garrisons selected for participation. The military garrisons included in this study were proportionally representative of the CAF by geographic region. Military companies and individuals within the selected garrisons were randomly chosen to participate in the study. Demographic and behavioral risk data were collected from September-November 2011 using personal interviews. Blood was collected for HIV and syphilis testing. Of 2,523 participants tested, 6.0% screened positive for HIV [includes 5.3% who screened positive for HIV only and 0.7% who screened positive for both HIV and syphilis], and 3.1% screened positive for syphilis only. Analyses examining risk factors associated with HIV/syphilis infection (i.e., infected with HIV, infected with syphilis, or co-infected with both HIV and syphilis) were restricted to 2,255 men who reported ever having sex. In a multivariate logistic regression model, the odds of testing positive for HIV/syphilis were higher among men who were separated, divorced, or widowed (adjusted odds ratio [AOR]=3.13, 95% confidence interval [CI]: 1.24-7.89), had sex with sex workers (AOR=1.64, 95% CI: 1.19-2.27), and reported a genital sore/ulcer in the past 12 months preceeding the survey (AOR=1.73, 95% CI: 1.05-2.86). Higher HIV knowledge was protective against HIV/syphilis infection (AOR=0.73, 95% CI: 0.54-0.99). While the overall HIV prevalence in this sample of military personnel was lower than previously reported (6

  13. High levels of CD8-positive lymphocytes expressing CD45R0, granzyme B, and Ki-67 in lymph nodes of HIV-infected individuals are not associated with increased mortality

    DEFF Research Database (Denmark)

    Espersen, C; Pakkenberg, B; Harder, Eva

    2001-01-01

    -seropositive patients and seven HIV-negative patients. Eleven of the HIV-positive patients died within 78 months of biopsy time and 10 patients were alive on July 1, 1998. Double immunohistochemical staining procedures were developed to identify CD8(+) cells expressing CD45R0, granzyme B, and Ki-67. A stereological...... method was used to count the different cell types in the lymph nodes. There were no significant differences in the total cell (nucleated) and CD3(+) cell concentrations between the three groups. However, there were significantly higher concentrations of CD3(+)CD8(+), CD8(+)CD45R0(+), and CD8(+)Ki-67...... of biopsy time, were among the patients with the lowest concentrations of CD8(+)granzyme B(+) and CD8(+)Ki-67(+) lymphocytes. This finding allowed us to conclude that CD8(+) lymphocytes expressing high levels of CD45R0, granzyme B, and Ki-67 in lymph nodes of HIV patients are not related to increased...

  14. FEELINGS EXPRESSED BY WOMEN WITH HIV CLINICAL UNABLE TO BREASTFEED

    Directory of Open Access Journals (Sweden)

    Michelle Larissa Andrade Sousa

    2009-05-01

    Full Text Available In clinical practice are restricted conditions that no-indicated definitively the breastfeeding. Therefore, this study addresses the objectives: know the sentiments expressed by women with HIV clinical failure to breastfeed; describe the importance of the mother and child contact in breastfeeding, as well as reporting the alternatives encountered by mothers to compensate for the deprivation of this practice. Therefore this research is characterized as descriptive exploratory qualitative in nature. Taking as a sample 10 women who had already passed the period of breast feeding at the breast, using the Reference Center for STD / AIDS in the municipality of Jequié / Ba. The instrument for data collection was the form, which was filled from the signing of the term of Free and Informed Consent built for this purpose. Data analysis was submitted to the technical analysis of the Content of Bardin, from which emerged the categories and subcategories: Feelings Sentimentos manifestados por mulheres com HIV (sadness, helplessness, shame, despair, guilt; importance of breastfeeding (prevention of diseases and exchange of affection and finally, strategy to compensate for the deprivation of breastfeeding (offering more care and attention. Given the foregoing concluded that the HIV positive mothers in addition to carrying this condition throughout his life, which has already lead to a significant blow in their emotions, they had to give up breastfeeding natural - by which time the woman was fully realizes mother - leading the lastimosas express the same experiences, mainly by various understand the benefits of breast milk as much as nutritional immunological and psychological for the baby. This reality serves as incentive for reflection on the part of health professionals to see these women on a holistic and natural in these children as defenceless beings who require more care and attention.

  15. Live attenuated measles vaccine expressing HIV-1 Gag virus like particles covered with gp160ΔV1V2 is strongly immunogenic

    International Nuclear Information System (INIS)

    Guerbois, Mathilde; Moris, Arnaud; Combredet, Chantal; Najburg, Valerie; Ruffie, Claude; Fevrier, Michele; Cayet, Nadege; Brandler, Samantha; Schwartz, Olivier; Tangy, Frederic

    2009-01-01

    Although a live attenuated HIV vaccine is not currently considered for safety reasons, a strategy inducing both T cells and neutralizing antibodies to native assembled HIV-1 particles expressed by a replicating virus might mimic the advantageous characteristics of live attenuated vaccine. To this aim, we generated a live attenuated recombinant measles vaccine expressing HIV-1 Gag virus-like particles (VLPs) covered with gp160ΔV1V2 Env protein. The measles-HIV virus replicated efficiently in cell culture and induced the intense budding of HIV particles covered with Env. In mice sensitive to MV infection, this recombinant vaccine stimulated high levels of cellular and humoral immunity to both MV and HIV with neutralizing activity. The measles-HIV virus infected human professional antigen-presenting cells, such as dendritic cells and B cells, and induced efficient presentation of HIV-1 epitopes and subsequent activation of human HIV-1 Gag-specific T cell clones. This candidate vaccine will be next tested in non-human primates. As a pediatric vaccine, it might protect children and adolescents simultaneously from measles and HIV.

  16. Membrane expression of MRP-1, but not MRP-1 splicing or Pgp expression, predicts survival in patients with ESFT.

    Science.gov (United States)

    Roundhill, E; Burchill, S

    2013-07-09

    Primary Ewing's sarcoma family of tumours (ESFTs) may respond to chemotherapy, although many patients experience subsequent disease recurrence and relapse. The survival of ESFT cells following chemotherapy has been attributed to the development of resistant disease, possibly through the expression of ABC transporter proteins. MRP-1 and Pgp mRNA and protein expression in primary ESFTs was determined by quantitative reverse-transcriptase PCR (RT-qPCR) and immunohistochemistry, respectively, and alternative splicing of MRP-1 by RT-PCR. We observed MRP-1 protein expression in 92% (43 out of 47) of primary ESFTs, and cell membrane MRP-1 was highly predictive of both overall survival (PMRP-1 was detected in primary ESFTs, although the pattern of splicing variants was not predictive of patient outcome, with the exception of loss of exon 9 in six patients, which predicted relapse (P=0.041). Pgp protein was detected in 6% (38 out of 44) of primary ESFTs and was not associated with patient survival. For the first time we have established that cell membrane expression of MRP-1 or loss of exon 9 is predictive of outcome but not the number of splicing events or expression of Pgp, and both may be valuable factors for the stratification of patients for more intensive therapy.

  17. Modelling self-assessed vulnerability to HIV and its associated factors in a HIV-burdened country.

    Science.gov (United States)

    Fagbamigbe, A F; Lawal, A M; Idemudia, E S

    2017-12-01

    Globally, individuals' self-assessment of vulnerability to HIV infection is important to maintain safer sexual behaviour and reduce risky behaviours. However, determinants of self-perceived risk of HIV infection are not well documented and differ. We assessed the level of self-perceived vulnerability to HIV infection in Nigeria and also identified its risk factors. We explored a recent nationally representative data with self-reported vulnerability ('high', 'low' and 'no risk at all') to HIV infection as the outcome of interest. Data were weighted and association between the outcomes and the risk factors determined. We used simple ordered logit regression to model relationship between the outcome variable and risk factors, and controlled for the significant variables in multiple ordered logistic regression at 5% significance level. About 74% had good knowledge of HIV transmission and 6% had experienced STI recently. The likelihood of assessing oneself as having 'no risk at all' was 50% and for 'high chances' was 1.6%. Self-perceived high risk of HIV was higher among those who recently experienced STI (5.6%) than those who did not (1.7%), and also higher among those who recently engaged in transactional sex and had multiple sexual partners. The odds of good knowledge of HIV transmission on high self-perceived vulnerability to HIV was 19% higher than poor knowledge (OR = 1.19, 95% CI: 1.12-1.27). Also, respondents who recently had multiple sexual partners were 72% (OR = 1.72, 95% CI: 1.60-1.86) more likely to report self as having high risk. Younger respondents aged 14-19 years had higher odds of 41% (OR = 1.41, 95% CI: 1.29-1.55) to perceive self as having high vulnerability to HIV than older respondents. High vulnerability to HIV infection was reported among younger respondents, those with history of STIS and those who engage in multiple sexual relations. Despite high level of risky sexual behaviour and good knowledge of HIV transmission and prevention

  18. Oligodendrocyte Injury and Pathogenesis of HIV-1-Associated Neurocognitive Disorders

    Directory of Open Access Journals (Sweden)

    Han Liu

    2016-07-01

    Full Text Available Oligodendrocytes wrap neuronal axons to form myelin, an insulating sheath which is essential for nervous impulse conduction along axons. Axonal myelination is highly regulated by neuronal and astrocytic signals and the maintenance of myelin sheaths is a very complex process. Oligodendrocyte damage can cause axonal demyelination and neuronal injury, leading to neurological disorders. Demyelination in the cerebrum may produce cognitive impairment in a variety of neurological disorders, including human immunodeficiency virus type one (HIV-1-associated neurocognitive disorders (HAND. Although the combined antiretroviral therapy has markedly reduced the incidence of HIV-1-associated dementia, a severe form of HAND, milder forms of HAND remain prevalent even when the peripheral viral load is well controlled. HAND manifests as a subcortical dementia with damage in the brain white matter (e.g., corpus callosum, which consists of myelinated axonal fibers. How HIV-1 brain infection causes myelin injury and resultant white matter damage is an interesting area of current HIV research. In this review, we tentatively address recent progress on oligodendrocyte dysregulation and HAND pathogenesis.

  19. The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study

    Directory of Open Access Journals (Sweden)

    Poulton Joanna

    2009-04-01

    Full Text Available Abstract Background The mitochondrial DNA (mtDNA T16189C polymorphism, with a homopolymeric C-tract of 10–12 cytosines, is a putative genetic risk factor for idiopathic dilated cardiomyopathy in the African and British populations. We hypothesized that this variant may predispose to dilated cardiomyopathy in people who are infected with the human immunodeficiency virus (HIV. Methods A case-control study of 30 HIV-positive cases with dilated cardiomyopathy and 37 HIV-positive controls without dilated cardiomyopathy was conducted. The study was confined to persons of black African ancestry to minimize confounding of results by population admixture. HIV-positive patients with an echocardiographically confirmed diagnosis of dilated cardiomyopathy and HIV-positive controls with echocardiographically normal hearts were studied. Patients with secondary causes of cardiomyopathy (such as hypertension, diabetes, pregnancy, alcoholism, valvular heart disease, and opportunistic infection were excluded from the study. DNA samples were sequenced for the mtDNA T16189C polymorphism with a homopolymeric C-tract in the forward and reverse directions on an ABI3100 sequencer. Results The cases and controls were well matched for age (median 35 years versus 34 years, P = 0.93, gender (males 60% vs 53%, P = 0.54, and stage of HIV disease (mean CD4 T cell count 260.7/μL vs. 176/μL, P = 0.21. The mtDNA T16189C variant with a homopolymeric C-tract was detected at a frequency of 26.7% (8/30 in the HIV-associated cardiomyopathy cases and 13.5% (5/37 in the HIV-positive controls. There was no significant difference between cases and controls (Odds Ratio 2.33, 95% Confidence Interval 0.67–8.06, p = 0.11. Conclusion The mtDNA T16189C variant with a homopolymeric C-tract is not associated with dilated cardiomyopathy in black African people infected with HIV.

  20. HIV Distal Neuropathic Pain Is Associated with Smaller Ventral Posterior Cingulate Cortex.

    Science.gov (United States)

    Keltner, John R; Connolly, Colm G; Vaida, Florin; Jenkinson, Mark; Fennema-Notestine, Christine; Archibald, Sarah; Akkari, Cherine; Schlein, Alexandra; Lee, Jisu; Wang, Dongzhe; Kim, Sung; Li, Han; Rennels, Austin; Miller, David J; Kesidis, George; Franklin, Donald R; Sanders, Chelsea; Corkran, Stephanie; Grant, Igor; Brown, Gregory G; Atkinson, J Hampton; Ellis, Ronald J

    2017-03-01

    . Despite modern antiretroviral therapy, HIV-associated neuropathy is one of the most prevalent, disabling and treatment-resistant complications of HIV disease. The presence and intensity of distal neuropathic pain is not fully explained by the degree of peripheral nerve damage. A better understanding of brain structure in HIV distal neuropathic pain may help explain why some patients with HIV neuropathy report pain while the majority does not. Previously, we reported that more intense distal neuropathic pain was associated with smaller total cerebral cortical gray matter volumes. The objective of this study was to determine which parts of the cortex are smaller. . HIV positive individuals with and without distal neuropathic pain enrolled in the multisite (N = 233) CNS HIV Antiretroviral Treatment Effects (CHARTER) study underwent structural brain magnetic resonance imaging. Voxel-based morphometry was used to investigate regional brain volumes in these structural brain images. . Left ventral posterior cingulate cortex was smaller for HIV positive individuals with versus without distal neuropathic pain (peak P  = 0.017; peak t = 5.15; MNI coordinates x = -6, y = -54, z = 20). Regional brain volumes within cortical gray matter structures typically associated with pain processing were also smaller for HIV positive individuals having higher intensity ratings of distal neuropathic pain. . The posterior cingulate is thought to be involved in inhibiting the perception of painful stimuli. Mechanistically a smaller posterior cingulate cortex structure may be related to reduced anti-nociception contributing to increased distal neuropathic pain. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  1. Metabolic Abnormalities and Viral Replication is Associated with Biomarkers of Vascular Dysfunction in HIV-Infected Children

    Science.gov (United States)

    Miller, Tracie L.; Borkowsky, William; DiMeglio, Linda A.; Dooley, Laurie; Geffner, Mitchell E.; Hazra, Rohan; McFarland, Elizabeth J.; Mendez, Armando J.; Patel, Kunjal; Siberry, George K.; Van Dyke, Russell B.; Worrell, Carol J.; Jacobson, Denise L.

    2011-01-01

    Objectives Human immunodeficiency virus (HIV)-infected children may be at risk for premature cardiovascular disease. We compared levels of biomarkers of vascular dysfunction among HIV-infected children with and without hyperlipidemia to HIV-exposed, uninfected children (HEU) enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS), and determined factors associated with these biomarkers. Design Prospective cohort study Methods Biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP1)); coagulant dysfunction (fibrinogen and P-selectin); endothelial dysfunction (soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), and E-selectin); and metabolic dysfunction (adiponectin) were measured in 226 HIV-infected and 140 HEU children. Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity, and antiretroviral therapy were recorded. Results The median ages were 12.3 y (HIV-infected) and 10.1 y (HEU). Body mass index (BMI) Z-scores, waist and hip circumference, and percent body fat were lower among HIV-infected. Total and non-HDL cholesterol and triglycerides were higher in HIV-infected children. HIV-infected children had higher MCP-1, fibrinogen, sICAM, and sVCAM levels. In multivariable analyses in the HIV-infected children alone, BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and sVCAM. Unfavorable lipid profiles were positively associated with IL6, MCP1, fibrinogen, and P- and E-selectin, whereas increased HIV viral load was associated with markers of inflammation (MCP1 and CRP) and endothelial dysfunction (sICAM and sVCAM). Conclusions HIV-infected children have higher levels of biomarkers of vascular dysfunction than do HEU children. Risk factors associated with higher biomarkers include unfavorable lipid levels and active HIV replication. PMID:22136114

  2. HIV-1 vaccines

    Science.gov (United States)

    Excler, Jean-Louis; Robb, Merlin L; Kim, Jerome H

    2014-01-01

    The development of a safe and effective preventive HIV-1 vaccine remains a public health priority. Despite scientific difficulties and disappointing results, HIV-1 vaccine clinical development has, for the first time, established proof-of-concept efficacy against HIV-1 acquisition and identified vaccine-associated immune correlates of risk. The correlate of risk analysis showed that IgG antibodies against the gp120 V2 loop correlated with decreased risk of HIV infection, while Env-specific IgA directly correlated with increased risk. The development of vaccine strategies such as improved envelope proteins formulated with potent adjuvants and DNA and vectors expressing mosaics, or conserved sequences, capable of eliciting greater breadth and depth of potentially relevant immune responses including neutralizing and non-neutralizing antibodies, CD4+ and CD8+ cell-mediated immune responses, mucosal immune responses, and immunological memory, is now proceeding quickly. Additional human efficacy trials combined with other prevention modalities along with sustained funding and international collaboration remain key to bring an HIV-1 vaccine to licensure. PMID:24637946

  3. Factors Associated with HIV Related Stigma among College Students in the Midwest

    Directory of Open Access Journals (Sweden)

    Caroline Kingori

    2017-07-01

    Full Text Available In general, U.S. college students have low perceived susceptibility of acquiring HIV infection while 15–25 percent of youth have had negative perceptions towards HIV positive individuals. Factors associated with HIV stigma among college students were examined in a convenience sample of 200 students. Descriptive and inferential statistics were utilized to summarize the data. Only four percent of participants responded correctly to HIV transmission knowledge items. HIV transmission knowledge scores were significantly higher for participants who were single with partner and those who resided outside university residential dorms (p < 0.05