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Interleukin 6 (IL-6) activates cells through its unique heterodimeric signaling complex of IL-6 receptor (IL6R) subunit and interleukin 6 signal transducer β-subunit glycoprotein 130 (gp130). The objective of this study was to investigate associations among serum levels of IL-6, sIL-6R, sgp130 and relative fluorescence intensity (RFI) of the α-subunit of the IL-6 receptor (CD126) on T-cells of HIV-1 infected and uninfected men. Blood samples were obtained from 69 HIV-1-infected men on Highly Active Antiretroviral Therapy (HAART) with mean age of 49.1 and 52 HIV-1-uninfected with mean age of 54.3 years -. All men were participating in the Los Angeles Multi-Center AIDS Cohort Study (MACS). Serum levels of IL-6, sIL-6R, sgp130 were measured by enzyme-linked immunoassays and T-cell phenotypic analysis and RFI of CD126 on CD4+ and CD8+ by flow cytometry. Mean serum levels of IL-6, sIL6R, sgp130 and of CD126 RFI on CD4+ were 4.34 pg/mL, 39.3 ng/mL, 349 ng/mL and 526 RFI respectively for HIV-1-infected men and 2.74 pg/mL, 41.9 ng/mL, 318 ng/mL and 561 RFI respectively for HIV-1-uninfected men. The mean serum concentrations of IL-6, sIL-6R in HIV-1-infected and uninfected men were not significantly different (p>0.05). There was a positive correlation between plasma HIV-1 RNA and the levels of IL-6 (p<0.001), sIL6R (p = 0.002) but no correlation with sgp130 (p = 0.339). In addition, there was a negative correlation between serum levels of IL-6 with RFI of CD126 on CD4+ (p = 0.037) and a positive correlation between serum levels of sgp130 (p = 0.021) and sIL-6R in HIV-1-infected men. Knowledge of biological variation, differences in the blood levels of biomarkers among healthy individuals and individuals experiencing illness, are very important for selection of appropriate tests for stage and progression of disease. Our data suggest no correlation among IL-6, and sIL-R6, in the treated phase of HIV-1 infection. The action and blood level of IL-6 and its receptors may be different at each stage of a disease progression.

Four factors have driven China's response to the HIV/AIDS pandemic: (1) existing government structures and networks of relationships; (2) increasing scientific information; (3) external influences that underscored the potential consequences of an HIV/AIDS pandemic and thus accelerated strategic planning; and (4) increasing political commitment at the highest levels. China's response culminated in legislation to control HIV/AIDS—the AIDS Prevention and Control Regulations. Three major initiatives are being scaled up concurrently. First, the government has prioritised interventions to control the epidemic in injection drug users, sex workers, men who have sex with men, and plasma donors. Second, routine HIV testing is being implemented in populations at high risk of infection. Third, the government is providing treatment for infected individuals. These bold programmes have emerged from a process of gradual and prolonged dialogue and collaboration between officials at every level of government, researchers, service providers, policymakers, and politicians, and have led to decisive action.

Background Cytokines, chemokines, adipocytokines, soluble cell receptors, and immune activation markers play an important role in immune responsiveness and can provide prognostic value since they reflect underlying conditions and disease states. This study was undertaken to investigate the components of biological variation for various laboratory tests of blood immunological biomarkers. Results Estimates of intra-individual coefficient of variation (CV I ) and inter-individual coefficient of variation (CV G ) were examined for blood immunological biomarkers. Biomarkers with CV I  < 10% for both genders were CD3, CD4, and CD8 T-cells, serum levels of soluble cluster of differentiation 14 (sCD14), sCD163, and soluble glycoprotein 130 (sgp130). The CV I for serum levels of adiponectin, interleukin-1 receptor antagonist (IL-1Ra), macrophage inflammatory protein 1 beta (MIP-1β), soluble CD40 Ligand (sCD40L), soluble interleukin-2 receptor alpha (sIL-2Rα), soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor receptor II (sTNF-RII), and tumor necrosis factor alpha (TNF-α) were between 11 and 20%. Biomarkers with CV G  < 20% were CD3 T-cell, and serum concentrations of sCD14, sCD40L, and sgp130. The biomarkers with CV G  > 40% were adiponectin, IL-1ra, leptin, MIP-1β, sCD163, and sIL-2Rα. Conclusion The biological variations of biomarkers have important monitoring value for longitudinal investigation and are essential for quality specification of tests that are performed in the laboratory. The CV I was relatively small while CV G was comparatively large and mean values of each biomarker vary between subjects. The individuality of biomarkers significantly influences reference interval values. A majority of the biomarkers in this study had strong individuality and the result of each biomarker should be cautiously interpreted if using established reference interval values. Comparison of a patient’s test result with previous ones may be more useful than the usage of conventional reference values.

Although increasingly studied in high-income countries, there is a paucity of data from the Chinese population on the patterns of cancer among people living with HIV (PLHIV). We conducted a nationwide follow-up study using routinely collected data for adult PLHIV diagnosed on or before 31 December 2011 and alive and in care as of 1 January 2008. Participants were observed from 1 January 2008 (study start) to 30 June 2012 (study end). Main outcome measures were gender-stratified age-standardized incidence rates for China (ASIRC) and standardized incidence ratios (SIR) for all malignancy types/sites observed. Among 399,451 subjects, a majority was aged 30-44 years (49.3%), male (69.8%), and Han Chinese (67.9%). A total of 3,819 reports of cancer were identified. Overall, ASIRC was 776.4 per 100,000 for males and 486.5 per 100,000 for females. Malignancy sites/types with highest ASIRC among males were lung (226.0 per 100,000), liver (145.7 per 100,000), and lymphoma (63.1 per 100,000), and among females were lung (66.8 per 100,000), lymphoma (48.0 per 100,000), stomach (47.8 per 100,000), and cervix (47.6 per 100,000). Overall SIR for males was 3.4 and for females was 2.6. Highest SIR was observed for Kaposi sarcoma (2,639.8 for males, 1,593.5 for females) and lymphoma (13.9 for males, 16.0 for females). These results provide evidence of substantial AIDS-defining and non-AIDS-defining cancer burden among adult Chinese PLHIV between 2008 and 2011. Although further study is warranted, China should take action to improve cancer screening, diagnosis, and treatment for this vulnerable population.

People living with HIV (PLWH) are at higher risk of developing lymphoma. In this study, we performed cytometry by time-of-flight (CyTOF) on peripheral blood mononuclear cells of cART-naïve HIV+ individuals and cART-naïve HIV+ individuals prior to AIDS-associated non-Hodgkin lymphoma (pre-NHL) diagnosis. Participants were enrolled in the Los Angeles site of the MACS/WIHS Combined Cohort Study (MWCCS). Uniform Manifold Approximation and Projection (UMAP) and unsupervised clustering analysis were performed to identify differences in the expression of B-cell activation markers and/or oncogenic markers associated with lymphomagenesis. CD10 + CD27 - B cells, CD20 + CD27 - B cells, and B-cell populations with aberrant features (CD20 + CD27 + CXCR4 + CD71 + B cells and CD20 + CXCR4 + cMYC + B cells) were significantly elevated in HIV+ cART-naïve compared to HIV-negative samples. CD20 + CD27 + CD24 + CXCR4 + CXCR5 + B cells, CD20 + CD27 + CD10 + CD24 + CXCR4 + cMYC + B cells, and a cluster of CD20 + CXCR4 hi CD27 - CD24 + CXCR5 + CD40 + CD4 + AICDA + B cells were significantly elevated in HIV+ pre-NHL (cART-naïve) compared to HIV+ cART-naïve samples. A potentially clonal cluster of CD20 + CXCR4 + CXCR5 + cMYC + AICDA + B cells and a cluster of germinal center B-cell-like cells (CD19 - CD20 + CXCR4 + Bcl-6 + PD-L1 + cMYC + ) were also found in the circulation of HIV+ pre-NHL (cART-naïve) samples. Moreover, significantly elevated clusters of CD19 + CD24 hi CD38 hi cMYC + AICDA + B regulatory cells were identified in HIV+ pre-NHL (cART-naïve) compared to HIV+ cART-naïve samples. The present study identifies unique B-cell subsets in PLWH with potential pre-malignant features that may contribute to the development of pre-tumor B cells in PLWH and that may play a role in lymphomagenesis.

Background: Asymptomatic Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhea) infections pose diagnostic and control problems in developing countries. Methods: Participants in China, India, Peru, Russia, and Zimbabwe were screened for C. trachomatis and N. gonorrhoeae infections and symptoms. Results: A total of 18,014 participants were evaluated at baseline, 15,054 at 12 months, and 14,243 at 24 months. The incidence of chlamydia in men was 2.0 per 100 person years both from baseline to 12 months and from 12 to 24 months, and in women, 4.6 from baseline to 12 months and 3.6 from 12 to 24 months; a range of 31.2% to 100% reported no symptoms across the 5 countries. The incidence of gonorrhea in men was 0.3 per 100 person years both from baseline to 12 months and from 12 to 24 months, and in women, 1.4 from baseline to 12 months and 1.1 from 12 to 24 months; a range of 66.7% to 100% reported no symptoms. Being female, aged 18 to 24 years, and having more than 1 partner were associated with both the infections. In addition, being divorced, separated, or widowed was associated with gonorrhea. Being male, having 6+ years of education, and reporting only 1 partner were associated with having no symptoms among those infected with chlamydia. No variables correlated with asymptomatic gonorrhea among those infected. Conclusion: A high prevalence and incidence of asymptomatic sexually transmitted infections was identified among men and women in a wide variety of settings. More effective programs are needed to identify and treat chlamydia and gonorrhea infections, especially among women, young adults, those with multiple partners, those repeatedly infected, and particularly those at risk without symptoms. The risk of transmission from persons with no symptoms requires further study.

Background COPD and impairment in diffusing capacity for carbon monoxide (DLCO) are common comorbidities in people with HIV (PWH). HIV may increase susceptibility to inhaled toxins including air pollution. In PWH and people without HIV (PWoH), we investigated whether air pollution exposure was associated with within-group differences in lung function or respiratory symptoms, and whether these associations differed by HIV serostatus or the presence of underlying lung disease. Methods We analyzed cross-sectional data from the Multicenter AIDS Cohort Study (MACS) and the Women’s Interagency HIV Study (WIHS), including participants with pulmonary function tests and accompanying standardized respiratory questionnaires in 2017–2020. The participants were linked to fine particulate matter (PM 2.5 ) and ozone exposure data. Associations between exposures and respiratory outcomes were quantified with regression models. Two subgroup analyses were conducted, restricting to individuals with COPD (FEV 1 /FVC ratio < 0.7) or impaired DLCO (< 80% predicted). Results 338 MACS participants and 1073 WIHS participants were included. Overall, there were no significant associations between pollution exposures and either lung function or respiratory symptoms. In PWH with COPD, 1 µg/m 3 greater exposure to PM 2.5 was associated with worse St. George’s Respiratory Questionnaire (SGRQ) score (4.04 points; 95% CI 0.36–7.72) and worse modified Medical Research Council (mMRC) dyspnea score (0.28 points; 95% CI 0.02–0.53). In PWH with impaired DLCO, 1 µg/m 3 greater PM 2.5 exposure was associated with worse SGRQ (2.14 points, 95% CI 0.2–4.08) and mMRC (0.16 points, 95% CI 0.02–0.29). There were no significant associations between PM 2.5 and respiratory symptoms in PWoH with COPD or impaired DLCO. Ozone exposure was not associated with respiratory symptoms in PWH or PWoH. Conclusions PM 2.5 exposure may act synergistically with HIV infection to worsen respiratory symptoms in people with chronic lung disease. Further study is needed to determine if air pollution leads to decline in lung function in PWH.

Multistage stepwise HIV testing and treatment initiation procedures can result in lost opportunities to provide timely antiretroviral therapy (ART). Incomplete patient engagement along the continuum of HIV care translates into high levels of preventable mortality. We aimed to evaluate the ability of a simplified test and treat structural intervention to reduce mortality. In the \"pre-intervention 2010\" (from January 2010 to December 2010) and \"pre-intervention 2011\" (from January 2011 to December 2011) phases, patients who screened HIV-positive at health care facilities in Zhongshan and Pubei counties in Guangxi, China, followed the standard-of-care process. In the \"post-intervention 2012\" (from July 2012 to June 2013) and \"post-intervention 2013\" (from July 2013 to June 2014) phases, patients who screened HIV-positive at the same facilities were offered a simplified test and treat intervention, i.e., concurrent HIV confirmatory and CD4 testing and immediate initiation of ART, irrespective of CD4 count. Participants were followed for 6-18 mo until the end of their study phase period. Mortality rates in the pre-intervention and post-intervention phases were compared for all HIV cases and for treatment-eligible HIV cases. A total of 1,034 HIV-positive participants (281 and 339 in the two pre-intervention phases respectively, and 215 and 199 in the two post-intervention phases respectively) were enrolled. Following the structural intervention, receipt of baseline CD4 testing within 30 d of HIV confirmation increased from 67%/61% (pre-intervention 2010/pre-intervention 2011) to 98%/97% (post-intervention 2012/post-intervention 2013) (all p < 0.001 [i.e., for all comparisons between a pre- and post-intervention phase]), and the time from HIV confirmation to ART initiation decreased from 53 d (interquartile range [IQR] 27-141)/43 d (IQR 15-113) to 5 d (IQR 2-12)/5 d (IQR 2-13) (all p < 0.001). Initiation of ART increased from 27%/49% to 91%/89% among all cases (all p < 0.001) and from 39%/62% to 94%/90% among individuals with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). Mortality decreased from 27%/27% to 10%/10% for all cases (all p < 0.001) and from 40%/35% to 13%/13% for cases with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). The simplified test and treat intervention was significantly associated with decreased mortality rates compared to pre-intervention 2011 (adjusted hazard ratio [aHR] 0.385 [95% CI 0.239-0.620] and 0.380 [95% CI 0.233-0.618] for the two post-intervention phases, respectively, for all newly diagnosed HIV cases [both p < 0.001], and aHR 0.369 [95% CI 0.226-0.603] and 0.361 [95% CI 0.221-0.590] for newly diagnosed treatment-eligible HIV cases [both p < 0.001]). The unit cost of an additional patient receiving ART attributable to the intervention was US$83.80. The unit cost of a death prevented because of the intervention was US$234.52. Our results demonstrate that the simplified HIV test and treat intervention promoted successful engagement in care and was associated with a 62% reduction in mortality. Our findings support the implementation of integrated HIV testing and immediate access to ART irrespective of CD4 count, in order to optimize the impact of ART.