Analysis of Galectin-Binding Receptors on B Cells Chakraborty, Asmi; Mohammed, Norhan B B; Bernasconi, Angela E ...
Methods in molecular biology (Clifton, N.J.),
2022, Volume:
2442
Journal Article
Open access
The reported roles of the β-galactoside-binding lectin family, known as galectins, in disease development have been advancing at a remarkable pace. Galectins and their glycan counter-receptor ligands ...are now considered key functional determinants in malignant and metastatic progression, tumor immune evasion, autoimmunity, and immune homeostasis. Their influence in these processes is elicited through coordinated expression in tumor, immune and stromal cellular compartments. While analysis of galectin levels in related research efforts is routinely performed through immunoassays and RT-qPCR, detection, and identification of glycan counter-receptor ligands in their native form on the cell surface has lagged. In this report, we present methods to detect and identify glycan counter-receptor ligands to galectin (Gal)-3 and Gal-9-two galectins at the crosshairs of cancer and immunology research. As a model, we will describe (1) isolation of human B-cell subsets from fresh tonsil tissue, (2) assaying of Gal-3/-9-binding activities on human B cells, and (3) identifying Gal-3/-9 ligands on human B-cell surfaces. These methods, of course, can be implemented on any cell type to provide a cellular and molecular context capable of transmitting a galectin-mediated phenotype. Establishing a galectin-binding activity on specific counter-receptor ligand(s) can help unearth potential critical determinants capable of delivering cellular signals required for disease progression. These advances open new avenues of research investigation that result in novel therapeutic targets and approaches.
Background and Objectives
Combination antiretroviral therapy (cART) is changing, and this may affect the type and occurrence of side effects. We examined the frequency of lipodystrophy (LD) and ...weight changes in relation to the use of specific drugs in the Swiss HIV Cohort Study (SHCS).
Methods
In the SHCS, patients are followed twice a year and scored by the treating physician as having ‘fat accumulation’, ‘fat loss’, or neither. Treatments, and reasons for change thereof, are recorded. Our study sample included all patients treated with cART between 2003 and 2006 and, in addition, all patients who started cART between 2000 and 2003.
Results
From 2003 to 2006, the percentage of patients taking stavudine, didanosine and nelfinavir decreased, the percentage taking lopinavir, nevirapine and efavirenz remained stable, and the percentage taking atazanavir and tenofovir increased by 18.7 and 22.2%, respectively.
In life‐table Kaplan–Meier analysis, patients starting cART in 2003–2006 were less likely to develop LD than those starting cART from 2000 to 2002 (P<0.02). LD was quoted as the reason for treatment change or discontinuation for 4% of patients on cART in 2003, and for 1% of patients treated in 2006 (P for trend <0.001). In univariate and multivariate regression analysis, patients with a weight gain of ≥5 kg were more likely to take lopinavir or atazanavir than patients without such a weight gain odds ratio (OR) 2, 95% confidence interval (CI) 1.3–2.9, and OR 1.7, 95% CI 1.3–2.1, respectively.
Conclusions
LD has become less frequent in the SHCS from 2000 to 2006. A weight gain of more than 5 kg was associated with the use of atazanavir and lopinavir.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Increasing obesity rates in Swiss HIV+ persons may partially be due to aging, demographic changes and earlier ART start. Most BMI increase occurred in year 1 of ART. The effect of individual ART ...regimens was limited.
Background.
The factors that contribute to increasing obesity rates in human immunodeficiency virus (HIV)-positive persons and to body mass index (BMI) increase that typically occurs after starting antiretroviral therapy (ART) are incompletely characterized.
Methods.
We describe BMI trends in the entire Swiss HIV Cohort Study (SHCS) population and investigate the effects of demographics, HIV-related factors, and ART on BMI change in participants with data available before and 4 years after first starting ART.
Results.
In the SHCS, overweight/obesity prevalence increased from 13% in 1990 (n = 1641) to 38% in 2012 (n = 8150). In the participants starting ART (n = 1601), mean BMI increase was 0.92 kg/m2 per year (95% confidence interval, .83–1.0) during year 0–1 and 0.31 kg/m2 per year (0.29–0.34) during years 1–4. In multivariable analyses, annualized BMI change during year 0–1 was associated with older age (0.15 0.06–0.24 kg/m2) and CD4 nadir <199 cells/µL compared to nadir >350 (P < .001). Annualized BMI change during years 1–4 was associated with CD4 nadir <100 cells/µL compared to nadir >350 (P = .001) and black compared to white ethnicity (0.28 0.16–0.37 kg/m2). Individual ART combinations differed little in their contribution to BMI change.
Conclusions.
Increasing obesity rates in the SHCS over time occurred at the same time as aging of the SHCS population, demographic changes, earlier ART start, and increasingly widespread ART coverage. Body mass index increase after ART start was typically biphasic, the BMI increase in year 0–1 being as large as the increase in years 1–4 combined. The effect of ART regimen on BMI change was limited.
Objectives
Women with HIV infection are mainly of reproductive age and need safe, effective and affordable contraception to avoid unintended pregnancies. The aim of this study was to evaluate ...contraceptive use and unintended pregnancies in this population in Switzerland.
Methods
A self‐report anonymous questionnaire on contraceptive methods, adherence to them, and unintended pregnancies was completed by women included in the Swiss HIV Cohort Study (SHCS) between November 2013 and June 2014. Sociodemographic characteristics and information related to combined antiretroviral therapy and HIV disease status were obtained from the SHCS database.
Results
Of 462 women included, 164 (35.5%) reported not using any contraception. Among these, 65 (39.6%) reported being sexually active, although 29 (44.6%) were not planning a pregnancy. Of 298 women using contraception, the following methods were reported: condoms, 219 (73.5%); oral hormonal contraception, 32 (10.7%); and intrauterine devices, 28 (9.4%). Among all women on contraception, 32 (10.7%) reported using more than one contraceptive method and 48 (16%) had an unintended pregnancy while on contraception (18, condoms; 16, oral contraception; four, other methods). Of these, 68.1% terminated the pregnancy and almost half (43.7%) continued using the same contraceptive method after the event.
Conclusions
Family planning needs in HIV‐positive women are not fully addressed because male condoms remained the predominant reported contraceptive method, with a high rate of unintended pregnancies. It is of utmost importance to provide effective contraception such as long‐acting reversible contraceptives for women living with HIV.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The evaluation of the prevalence of potential drug-drug interactions and assessment of their clinical relevance in patients' discharge medication in the medical ward of a community teaching hospital. ...The relevant clinical information was reported to the treating physicians.
200 patients at discharge from a medical ward were included. Prescribed drugs were analysed for interactions using commercially available software (Pharmavista). Clinical pharmacists and a physician assessed the clinical relevance of detected interactions, eliminated those which were not considered clinically relevant and formulated recommendations for those considered clinically relevant. A written recommendation was given to the physician to provide rapid feedback before discharge.
The median age of the 200 patients studied was 69 years. At discharge, patients took an average of 7 different drugs. 62.5% of patients had at least one potential drug-drug interaction. In total, 373 potential drug-drug interactions were identified: 223 (60%) of minor severity, 143 (38%) of moderate severity and 7 (2%) of major severity.
A computerised drug-drug interaction program (detection) together with clinical pharmacological experience (interpretation/evaluation) can be useful for decreasing the number of potentially harmful drug combinations. This approach may lead to an improvement in the quality of prescription, reducing possible risks and thus contributing to patient safety.
Objectives
To investigate delayed HIV diagnosis and late initiation of antiretroviral therapy (ART) in the Swiss HIV Cohort Study.
Methods
Two sub‐populations were included: 1915 patients with HIV ...diagnosis from 1998 to 2007 and within 3 months of cohort registration (group A), and 1730 treatment‐naïve patients with CD4≥200 cells/μL before their second cohort visit (group B). In group A, predictors for low initial CD4 cell counts were examined with a median regression. In group B, we studied predictors for CD4<200 cells/μL without ART despite cohort follow‐up.
Results
Median initial CD4 cell count in group A was 331 cells/μL; 31% and 10% were <200 and <50 cells/μL, respectively. Risk factors for low CD4 count were age and non‐White race. Homosexual transmission, intravenous drug use and living alone were protective. In group B, 30% initiated ART with CD4≥200 cells/μL; 18% and 2% dropped to CD4 <200 and <50 cells/μL without ART, respectively. Sub‐Saharan origin was associated with lower probability of CD4 <200 cells/μL without ART during follow‐up. Median CD4 count at ART initiation was 207 and 253 cells/μL in groups A and B, respectively.
Conclusions
CD4<200 cells/μL and, particularly, CD4<50 cells/μL before starting ART are predominantly caused by late presentation. Earlier HIV diagnosis is paramount.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
In the Swiss HIV Cohort Study, the number of people who inject drugs with replicating hepatitis C virus (HCV) infection decreased substantially after the introduction of direct-acting antivirals ...(DAAs). Among men who have sex with men, the increase in DAA uptake and efficacy was counterbalanced by frequent incident HCV infections.
The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited ...compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships.
The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods.
Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1–3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33–46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4–2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up).
Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV.
National Institute for Health Research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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