Current Issue : January - March Volume : 2015 Issue Number : 1 Articles : 6 Articles
Background: HIV-1 entry into host cells is mediated by interactions between the virus envelope glycoprotein\n(gp120/gp41) and host-cell receptors. N-glycans represent approximately 50% of the molecular mass of gp120 and\nserve as potential antigenic determinants and/or as a shield against immune recognition. We previously reported\nthat N-glycosylation of recombinant gp120 varied, depending on the producer cells, and the glycosylation variability\naffected gp120 recognition by serum antibodies from persons infected with HIV-1 subtype B. However, the impact\nof gp120 differential glycosylation on recognition by broadly neutralizing monoclonal antibodies or by polyclonal\nantibodies of individuals infected with other HIV-1 subtypes is unknown.\nMethods: Recombinant multimerizing gp120 antigens were expressed in different cells, HEK 293T, T-cell,\nrhabdomyosarcoma, hepatocellular carcinoma, and Chinese hamster ovary cell lines. Binding of broadly neutralizing\nmonoclonal antibodies and polyclonal antibodies from sera of subtype A/C HIV-1-infected subjects with individual\ngp120 glycoforms was assessed by ELISA. In addition, immunodetection was performed using Western and dot blot\nassays. Recombinant gp120 glycoforms were tested for inhibition of infection of reporter cells by SF162 and YU.2\nEnv-pseudotyped R5 viruses.\nResults: We demonstrated, using ELISA, that gp120 glycans sterically adjacent to the V3 loop only moderately\ncontribute to differential recognition of a short apex motif GPGRA and GPGR by monoclonal antibodies F425 B4e8 and\n447-52D, respectively. The binding of antibodies recognizing longer peptide motifs overlapping with GPGR epitope\n(268 D4, 257 D4, 19b) was significantly altered. Recognition of gp120 glycoforms by monoclonal antibodies specific for\nother than V3-loop epitopes was significantly affected by cell types used for gp120 expression. These epitopes included\nCD4-binding site (VRC03, VRC01, b12), discontinuous epitope involving V1/V2 loop with the associated glycans (PG9,\nPG16), and an epitope including V3-base-, N332 oligomannose-, and surrounding glycans-containing epitope (PGT 121).\nMoreover, the different gp120 glycoforms variably inhibited HIV-1 infection of reporter cells.\nConclusion: Our data support the hypothesis that the glycosylation machinery of different cells shapes gp120\nglycosylation and, consequently, impacts envelope recognition by specific antibodies as well as the interaction of HIV-1\ngp120 with cellular receptors. These findings underscore the importance of selection of appropriately glycosylated\nHIV-1 envelope as a vaccine antigen....
Background: HCV RNA viral load is an important predictor of sustained virological response and, recently, a significant\ncorrelation with liver fibrosis was described. We investigated on possible influence of clinical and viro-immunological\nvariables on HCV viral load in HIV-HCV co-infected patients over a study time of three years (2009-2012).\nMethods: We retrospectively enrolled 98 adult patients with a diagnosis of chronic HIV infection in 2009, a diagnosis of\nchronic HCV infection with a detectable plasma HCV RNA in 2009 and 2012, HCV therapy-na�¯ve or with failed and\nstopped antiviral treatment before June 2008. The following variables were recorded: age, gender, HCV genotype, IL28B\nrs12979860 CC genotype, HCV treatment status, advanced liver fibrosis diagnosis, antiretroviral therapy, CD4+ cell count,\nHCV viral load, HIV RNA (plasma HIV-1 RNA levels were measured from blood samples every three months at least). The\ncorrelation was established using linear regression analysis, analysis of variance and Fisherâ��s exact test. Comparisons\nbetween groups were performed using Fisherâ��s exact test, the independent samples t-test and the t-test for paired data,\nas appropriate, for continuous variables. A mixed mode (ME) maximum likelihood linear regression model was\nconstructed to evaluate the dependence of HCV viral load.\nResults: HCV RNA levels did not change significantly from 2009 to 2012 (from 3924650 �± 5320177 IU/ml to 3085128 �±\n3372347 IU/ml, p = 0.13); the CD4+ count increased significantly (from a mean of 576 to a mean of 654, p = 0.003). Using\nlinear regression, a positive correlation was observed for HCV load and genotype 1 (p = 0.002), nonresponder status\n(p = 0.04) and with interleukin 28B CC allele (p = 0.05). Other studied covariates failed to reach a significant correlation.\nConclusions: The HCV RNA load, a known pretreatment predictor of response to antiviral therapy, was independent of\nthe two main parameters of HIV disease, plasma HIV RNA and CD4 cell count, over an observation time of 3 years in\npatients with recovered or spontaneously maintained immunocompetence....
The 2014 International Symposium on HIV and Emerging Infectious Diseases (ISHEID) provided a forum for\ninvestigators to hear the latest research developments in the clinical management of HIV and HCV infections as\nwell as HIV cure research. Combined anti-retroviral therapy (c-ART) has had a profound impact on the disease\nprognosis and transformed this infection into a chronic disease. However, HIV is able to persist within the infected\nhost and the pandemic is still growing. The main 2014 ISHEID theme was, hence ââ?¬Å?Together for a world without\nHIV and AIDSââ?¬Â. In this report we not only give details on this main topic but also summarize what has been\ndiscussed in the areas of HCV coinfection and present a short summary on currently emerging viral diseases....
Introduction: Despite recommendations by the Centers for Disease Control (CDC) that all adults be offered\nnon-targeted HIV screening in all care settings, screening in acute-care settings remains unacceptably low. We\nperformed an observational study to evaluate an HIV screening pilot in an academic-community partnership health\ncenter urgent care clinic.\nMethods: We collected visit data via encounter forms and demographic and laboratory data from electronic\nmedical records. A post-pilot survey of perceptions of HIV screening was administered to providers and nurses.\nMultivariable analysis was used to identify factors associated with completion of testing.\nResults: Visit provider and triage nurse were highly associated with both acceptance of screening and completion\nof testing, as were younger age, male gender, and race/ethnicity. 23.5% of patients completed tests, although\n36.0% requested screening; time constraints as well as risk perceptions by both the provider and patient were cited\nas limiting completion of screening. Post-pilot surveys showed mixed support for ongoing HIV screening in this\nsetting by providers and little support by nurses.\nConclusions: Visit provider and triage nurse were strongly associated with acceptance of testing, which may reflect\nvariable opinions of HIV screening in this setting by clinical staff. Among patients accepting screening, visit provider\nremained strongly associated with completion of testing. Despite longstanding recommendations for non-targeted\nHIV screening, further changes to improve the testing and results process, as well as provider education and buy-in,\nare needed to improve screening rates....
The level (or frequency) of circulating monocyte subpopulations such as classical (CD14hiCD16?) and non-classical\n(CD14dimCD16+) monocytes varies during the course of HIV disease progression and antiretroviral therapy (ART).\nWe hypothesized that such variation and/or differences in the degree to which these cells expressed the\nimmunoregulatory enzyme, heme oxygenase-1 (HO-1), would be associated with CD4+ T cell recovery after the\ninitiation of ART. This hypothesis was tested in a cross-sectional study of four groups of HIV-infected subjects,\nincluding those who were seronegative, untreated virologic controllers [detectable viral load (VL) of <1000 copies/\nmL], untreated virologic non-controllers [VL > 10,000 copies/mL], and ART-mediated virologic controllers [VL < 75\ncopies/mL]. A longitudinal analysis of ART-treated subjects was also performed along with regression analysis to\ndetermine which biomarkers were associated with and/or predictive of CD4+ T cell recovery. Suppressive ART was\nassociated with increased levels of classical monocyte subpopulations (CD14hiCD16?) and decreased levels of\nnon-classical monocyte populations (CD14dimCD16+). Among peripheral blood mononuclear cells (PBMCs), HO-1\nwas found to be most highly up-regulated in CD14+ monocytes after ex vivo stimulation. Neither the levels of\nmonocyte subpopulations nor of HO-1 expression in CD14+ monocytes were significantly associated with the\ndegree of CD4+ T cell recovery. Monocyte subpopulations and HO-1 gene expression were, however, restored to\nnormal levels by suppressive ART. These results suggest that the level of circulating monocyte subpopulations and\ntheir expression of HO-1 have no evident relationship to CD4+ T cell recovery after the initiation of ART....
Background: Lipohypertrophy does not appear to be an adverse ART reaction while lipoatrophy is clearly\nassociated with the use of stavudine (d4T) and zidovudine (AZT). In low and middle income countries d4T has only\nrecently been phased out and AZT is still widely being used. Several case definitions have been developed to\ndiagnose lipodystrophy, but none of them are generalizable to sub-Saharan Africa where black women have less\nvisceral adipose tissue and more subcutaneous adipose tissue than white women. We aimed to develop a simple,\nobjective measure to define lipoatrophy and lipohypertrophy by comparing patient report to anthropometric and\ndual-energy X-ray absorptiometry (DXA) -derived variables.\nMethods: DXA and anthropometric measures were obtained in a cross sectional sample of black HIV-infected South\nAfrican men (n = 116) and women (n = 434) on ART. Self-reported information on fat gain or fat loss was collected\nusing a standard questionnaire. Receiver operating characteristic (ROC) curves were used to describe the performance\nof anthropometric and DXA-derived variables using patient reported lipoatrophy and lipohypertrophy as the reference\nstandard.\nResults: Lipoatrophy and lipohypertrophy were more common in women (25% and 33% respectively) than in men\n(10% and 13% respectively). There were insufficient numbers of men with DXA scans for meaningful analysis. The best\npredictors of lipoatrophy in women were the anthropometric variables tricep (AUC = 0.725) and thigh skinfold (AUC\n=0.720) thicknesses; and the DXA-derived variables percentage lower limb fat (AUC = 0.705) and percentage lower limb\nfat/height (AUC = 0.713). The best predictors of lipohypertrophy in women were the anthropometric variable waist/hip\nratio (AUC = 0.645) and the DXA-derived variable percentage trunk fat/percentage limb fat (AUC = 0.647).\nConclusions: We were able to develop simple, anthropometric measures for defining lipoatrophy and\nlipohypertrophy, using a sample of black HIV-infected South African women with DXA scans. This is of particular\nrelevance in resource limited settings, where health professionals need simple and inexpensive methods of diagnosing\npatients with lipoatrophy and lipohypertrophy....
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