Search Results (7)

Background: The rise in antimicrobial-resistant (AMR) strains of Neisseria gonorrhoeae is internationally recognised as a critical public health concern, with limited treatment options available. The urgency of this issue prompted the European Centre for Disease Prevention and Control to establish ‘EURO-GASP’ to monitor trends in resistance and address developments. Comprehensive data on AMR strains in people living with HIV (PLHIV) is limited, especially in Cyprus. Objectives: To analyse trends in rates of resistant N. gonorrhoeae infections and identify any correlations between patient factors that may contribute to such in PLHIV in The Republic of Cyprus. Methods: We conducted a retrospective chart review study on N. gonorrhoea resistance among PLHIV from the Gregorios HIV reference clinic in Larnaca, Cyprus, between 2015 and 2023. Antimicrobial susceptibility was assessed via disc diffusion or gradient strip method on GC II agar against a non-homogenous panel of antibiotic preparations, based on standard laboratory practice variation. Demographic and clinical data, including antibiograms, treatments and test of cure, were recorded. Statistical analysis was performed using Stata v16, with significance set at p < 0.05. The study received approval from the Cyprus National Bioethics Committee. Results: A total of 45 isolates from 39 patients were analysed, with 62% of these demonstrating resistance to at least one antibiotic. Resistance rates were not shown to change over time. We identified a statistically significant linear association between a person having a history of an STI and the number of antibiotics which the isolate is resistant to (β = 1.2; p: 0.004). Notably, a single isolate demonstrated resistance to ceftriaxone, the first-line treatment currently recommended in both Europe and the United States. This finding is particularly alarming given the critical role of ceftriaxone in the management of gonorrhoea. Conclusions: Whilst there has been no increase in resistance rates over time, the detection of ceftriaxone-resistant N. gonorrhoeae is a significant public health concern. Given that having a history of an STI makes a person more likely to develop a resistant infection, PLHIV or those who engage in risky sexual behaviours are particularly vulnerable. There is a pressing need to enhance surveillance and implement routine susceptibility testing in Cyprus, given the country’s role as a major international hub for travel and migration. Molecular analysis can further improve our understanding. Additionally, the global public health community must urgently prioritise the development of novel therapeutic agents for the treatment of gonorrhoea. Full article

Anti-human immunodeficiency virus (HIV) broadly neutralizing antibodies (bNAbs) offer a promising approach for the treatment of HIV-1. The current paradigm for antibody therapy involves passive antibody transfer, requiring regular delivery of bNAbs in treating chronic diseases such as HIV-1. An alternative strategy is to use AAV-mediated gene transfer to enable in vivo production of desirable anti-HIV-1 antibodies. In this study, we investigated two sets of triple combinations of AAV9-vectors encoding different bNAbs: N6, 10E8, 10-1074 (CombiMab1), and VRC07-523, PGDM1400, 10-1074 (CombiMab2). We used CBAxC57Bl and C57BL/6 mouse models to characterize rAAV-induced antibody expression and to evaluate the neutralization capacity of mouse sera against a global panel of HIV-1 viral strains. rAAV9-mediated IgG expression varied between bNAb clones and mouse strains, with C57BL/6 mice exhibiting higher bNAb titers following rAAV delivery. Although CombiMab2 treatment elicited a higher IgG titer than CombiMab1, both combinations resulted in neutralization of all the viral strains from the global HIV-1 panel. Our data highlight the potential of AAV vectors as a long-term option for HIV-1 therapy. Full article

Background: This study seeks to understand the empirical nature of macro-financial factors associated with the worsening of HIV infections and the risks that need to be carefully monitored for a sustainable improvement in HIV outcomes as developing countries seek to achieve the United Nations 95-95-95 targets. Methods: The author used a panel VAR model to study the long-term endogenous relationships between percentage changes in the annual spot price of the most traded commodities, GDP per capita, health spending, and the HIV infection rate of developing countries. Results: The author discovered that shocks of global commodity prices negatively impact GDP per capita, real government health spending, and real private health spending. These shocks have adverse spillover effects characterized by worsening HIV infections. The reactions from price shocks suggest that GDP per capita contract immediately when a commodity price shock hits developing economies. Real government health spending and real private health spending also contract instantly. HIV infections begin worsening three years after the shock in the energy and precious metal blocks of countries. HIV infections also begin to worsen two years after shocks in the agricultural block of counties. These impacts are statistically significant and can potentially reverse the positive HIV infection gains achieved in the previous years. Emergency funds, insurance schemes, and international aid for HIV need to discharge more funds to counter these shocks. Conclusions: There is a significant risk of reversing HIV infection outcomes arising from commodity price shocks. Funding agencies must protect HIV prevention services from global macro-economic shocks as countries move closer to the United Nations 95-95-95 targets. Full article

The use of broadly neutralizing antibodies (bNAbs) is a promising approach to HIV-1 treatment. In this work, we evaluate the neutralizing activity of the following HIV-1 bNAbs: VCR07-523, N6, PGDM1400, CAP256-VRC26.25, 10-1074, PGT128, 10E8, and DH511.11P, which are directed to different Env surface epitopes. We used the global panel of HIV-1 pseudoviruses to analyze the bNAbs’ potency and chose the most potent ones. To achieve maximum neutralization breadth and minimum IC₅₀ concentration, the most effective antibodies were tested in double and triple combinations. Among the doubles, the combinations of N6+PGDM1400 and N6+PGT128 with IC₅₀ ≤ 0.3 µg/mL proved to be the most effective. The most effective triple combination was N6+PGDM1400+PGT128. Our data demonstrate that this combination neutralizes pseudoviruses of the global HIV-1 panel with IC₅₀ ≤ 0.11 µg/mL and IC₈₀ ≤ 0.25 µg/mL. Full article

Background: Human immunodeficiency virus (HIV) is mainly detected in young, otherwise healthy, individuals. Cardiomyopathy and peripheral artery disease affecting these patients appears to be multifactorial. Prompt and potentially more effective implementation of therapeutic measures could be enabled by pre-symptomatic diagnosis of myocardial dysfunction and peripheral artery damage. However, limited data is available to date on this specific topic. Μethods: We investigated the association between global longitudinal strain (GLS), an established index of subclinical left ventricular systolic dysfunction (LVSD) assessed by two-dimensional speckle-tracking echocardiography, and: (a) patient history; (b) demographic and clinical baseline characteristics; (c) carotid intima-media thickness (IMT) and the presence of carotid atherosclerotic plaque(s), measured by ultrasonography; (d) temperature difference (ΔT) along each carotid artery, measured by microwave radiometry; and (e) basic blood panel measurements, including high-sensitivity troponin-T (hsTnT) and NT-proBNP in people living with HIV (PLWH) and no history of cardiovascular disease. Results: We prospectively enrolled 103 consecutive PLWH (95% male, age 47 ± 11 years, anti-retroviral therapy 100%) and 52 age- and sex-matched controls. PLWH had a significantly higher relative wall thickness (0.38 ± 0.08 vs. 0.36 ± 0.04, p = 0.048), and higher rate of LVSD (34% vs. 15.4%, p = 0.015), and carotid artery atherosclerosis (28% vs. 6%, p = 0.001) compared with controls. Among PLWH, LVSD was independently associated with the presence of carotid atherosclerosis (adj. OR:3.09; 95%CI:1.10–8.67, p = 0.032) and BMI (1.15; 1.03–1.29, p = 0.017), while a trend for association between LVSD and left ventricular hypertrophy was also noted (3.12; 0.73–13.33, p = 0.124). No differences were seen in microwave radiometry parameters, NT-proBNP, hs-TnT and c-reactive protein between PLWH with and without LVSD. Conclusions: Subclinical LVSD and carotid atherosclerosis were significantly more frequent in PLWH compared to a group of healthy individuals, implying a possible link between HIV infection and these two pathological processes. Carotid atherosclerosis and increased adiposity were independently associated with impaired GLS in HIV-infected individuals. Full article

The continued diversification of HIV poses potentially significant challenges to HIV diagnostics and therapeutics. The dynamic evolution of emerging variants is highlighted in countries such as Cameroon in West Central Africa, where all known subtypes and circulating recombinant forms (CRFs) have been shown to be prevalent. We obtained several hundred HIV-positive plasma and viruses from this region for characterization and identification of highly divergent HIV strains. A total of 163 viral strains were cultured to high titers and high volumes using donor peripheral blood mononuclear cells (PBMCs). Initially, 101 viruses representing 59 strains were well characterized and categorized. Results showed that the viral load (VL) range was 0.36–398.9 × 10⁷ copies/mL, p24 values was 0.2–1134 ng/mL. Phylogenetic analysis of thirty-six near full-length HIV-1 genomic sequences demonstrated that most recombinants were highly diverse CRF02 containing unique recombinant forms (URFs). There were seven viral isolates identified as pure subtype/sub-subtypes (F2, A1, G, and D), six as CRFs (CRF06, CRF18, and CRF22), and ten as URFs. These extensively characterized reagents reflect the current dynamic and complex HIV epidemic in Cameroon and provide valuable insights into the potential phylogenetic evolutionary trend of global HIV molecular epidemiology in the future. These materials may be useful for development of HIV validation and reference panels to evaluate the performance of serologic antigen and nucleic acid assays for their ability to detect and quantitate highly divergent HIV strains. Full article

The National Institute of Allergy and Infectious Diseases (NIAID) Virology Quality Assurance (VQA) established a robust proficiency testing program for Sanger sequencing (SS)-based HIV-1 drug resistance (HIVDR) testing in 2001. While many of the lessons learned during the development of such programs may also apply to next generation sequencing (NGS)-based HIVDR assays, challenges remain for the ongoing evaluation of NGS-based testing. These challenges include a proper assessment of assay accuracy and the reproducibility of low abundance variant detection, intra- and inter-assay performance comparisons among laboratories using lab-defined tests, and different data analysis pipelines designed for NGS. In collaboration with the World Health Organization (WHO) Global HIVDR Laboratory Network and the Public Health Agency of Canada, the Rush VQA program distributed archived proficiency testing panels to ten laboratories to evaluate internally developed NGS assays. Consensus FASTA files were submitted using 5%, 10%, and 20% variant detection thresholds, and scored based on the same criteria used for SS. This small study showed that the SS External Quality Assurance (EQA) approach can be used as a transitional strategy for using NGS to generate SS-like data and for ongoing performance while using NGS data from the same quality control materials to further evaluate NGS assay performance. Full article