Search Results (5,916)

The Caribbean continues to have high HIV prevalence globally with concurrently high mortality rates due to opportunistic Infections. This study addresses the prevalence of histoplasmosis and cryptococcosis among patients living with advanced HIV disease (AHD) in Trinidad and Tobago, focusing on the implementation of antigen-based diagnostic assays. Conducted as a cross-sectional survey across five HIV treatment sites, 199 participants with advanced HIV disease were enrolled between July 2022 and September 2023. Diagnostic testing was performed using the Clarus Histoplasma Galactomannan Enzyme Immunoassay (EIA), and the Immy CrAg^® LFA Cryptococcal Antigen Lateral Flow Assay on urine and blood samples, respectively. Results revealed that 14.6% of participants were found to be co-infected with either histoplasmosis or cryptococcosis, with histoplasmosis being more prevalent (10.5%) than cryptococcosis (4.0%). The study found no significant demographic differences between newly diagnosed and previously diagnosed participants. However, a lower median CD4 count was associated with a higher risk of fungal opportunistic infections. The findings underscore the critical role of systematic use of fungal antigen-based diagnostic assays among patients with AHD to improve the timely diagnosis and treatment of fungal infections among people living with HIV in resource-limited settings and to improve patient outcomes and survival. Full article

Background/Objectives: Mpox (monkeypox) is a zoonosis with origins in a currently unknown African reservoir. The first epidemiological accounts of mpox date back to the early 1980s, yet mpox only emerged as a pandemic threat in 2022–2023, more than 40 years later. This scenario is very different from those of other emerging diseases such as HIV and SARS, which immediately spread globally, in fully susceptible populations, starting from patients zero. Methods: We use mathematical modeling to illustrate the dynamics of mpox herd immunity in small communities in touch with the mpox natural reservoir. In particular, we employ an stochastic model. Results: The peculiar emergence of mpox can be explained by its relationship with smallpox, which was eradicated through universal mass vaccination in 1980. Mpox first emerged in small rural communities in touch with mpox’s animal reservoir and then spread globally. The relative isolation of these communities and their herd-immunity dynamics against mpox worked to delay the introduction of mpox in large urban centers. Conclusions: Mathematical modeling suggests that the search for the mpox animal reservoir would be most fruitful in communities with high mpox seroprevalence and small outbreaks. These are communities is tight contact with the mpox natural reservoir. We propose vaccinating individuals in communities in these communities to severely reduce the importation of cases elsewhere. Full article

Hepatitis delta virus (HDV) co-infections more often result in severe hepatitis compared to hepatitis B virus (HBV) infections alone. Despite a high HDV prevalence (7.1%), information regarding circulating HDV clades is very limited in Botswana. We extracted total nucleic acid from confirmed HDV-positive samples and quantified their viral load. We then sequenced the large hepatitis delta antigen (L-HDAg) using Oxford Nanopore Technology (ONT). Genotyping was performed using the HDV Database, and HDV mutation profiling was performed on AliView. All participants with HBV genotypic information belonged to sub-genotype A1, and 80% (4/5) of them had a higher HDV viral load and a lower HBV viral load. We sequenced 75% (9/12) of the HDV-positive samples, which belonged to HDV clade 8. A total of 54 mutations were discovered, with the most prevalent being Q148R (16%), D149P (16%) and G151D (16%). Known mutations such as S117A, K131R, R139K and G151D were detected, while the other mutations were novel. Our results reveal that HDV clade 8 is the predominant clade in Botswana. The significance of all mutations remains unclear. Future studies with a larger sample size to detect other HDV clades that might be circulating in Botswana and functionally characterize the detected mutations are warranted. Full article

Tsg101, a component of the endosomal sorting complex required for transport (ESCRT), is responsible for recognition of events requiring the machinery, as signaled by cargo tagging with ubiquitin (Ub), and for recruitment of downstream acting subunits to the site. Although much is known about the latter function, little is known about its role in the earlier event. The N-terminal domain of Tsg101 is a structural homologue of Ub conjugases (E2 enzymes) and the protein associates with Ub ligases (E3 enzymes) that regulate several cellular processes including virus budding. A pocket in the domain recognizes a motif, PT/SAP, that permits its recruitment. PT/SAP disruption makes budding dependent on Nedd4L E3 ligases. Using HIV-1 encoding a PT/SAP mutation that makes budding Nedd4L-dependent, we identified as critical for rescue the residues in the catalytic (HECT) domain of the E3 enzyme that lie in proximity to sites in Tsg101 that bind Ub non-covalently. Mutation of these residues impaired rescue by Nedd4L but the same mutations had no apparent effect in the context of a Nedd4 isomer, Nedd4-2s, whose N-terminal (C2) domain is naturally truncated, precluding C2-HECT auto-inhibition. Surprisingly, like small molecules that disrupt Tsg101 Ub-binding, small molecules that interfered with Nedd4 substrate recognition arrested budding at an early stage, supporting the conclusion that Tsg101–Ub–Nedd4 interaction promotes enzyme activation and regulates Nedd4 signaling for viral egress. Tsg101 regulation of E3 ligases may underlie its broad ability to function as an effector in various cellular activities, including viral particle assembly and budding. Full article

The leave-one-out (LOO) green fluorescent protein (GFP) approach to biosensor design combines computational protein design with split protein reconstitution. LOO-GFPs reversibly fold and gain fluorescence upon encountering the target peptide, which can be redefined by computational design of the LOO site. Such an approach can be used to create reusable biosensors for the early detection of emerging biological threats. Enlightening biophysical inferences for nine LOO-GFP biosensor libraries are presented, with target sequences from dengue, influenza, or HIV, replacing beta strands 7, 8, or 11. An initially low hit rate was traced to components of the energy function, manifesting in the over-rewarding of over-tight side chain packing. Also, screening by colony picking required a low library complexity, but designing a biosensor against a peptide of at least 12 residues requires a high-complexity library. This double-bind was solved using a “piecemeal” iterative design strategy. Also, designed LOO-GFPs fluoresced in the unbound state due to unwanted dimerization, but this was solved by fusing a fully functional prototype LOO-GFP to a fiber-forming protein, Drosophila ultrabithorax, creating a biosensor fiber. One influenza hemagglutinin biosensor is characterized here in detail, showing a shifted excitation/emission spectrum, a micromolar affinity for the target peptide, and an unexpected photo-switching ability. Full article

Background: Dried blood spots (DBSs) enable the study of serological markers of various pathogens without the need to obtain serum/plasma through venipuncture. Methods: Sixty-four blood samples were prepared on Whatman™ 903 cards using specimens obtained by venipuncture to study the detection of serological markers of diphtheria, tetanus, and pertussis in DBSs, and their stability 4 months post-collection. An automated chemiluminescent immunoassay was used to investigate diphtheria, tetanus, and pertussis IgG levels from both DBSs and plasma samples. Results: An optimal cut-off value for DBSs was calculated to improve the performance of diphtheria and tetanus serological markers in DBSs, achieving high sensitivity (95% and 98%, respectively) and specificity (91.7% and 92.3%, respectively). No protection against pertussis was found in the population studied. The correlation observed between the plasma and the DBSs processed after sample collection was high (0.967–0.970) for all antibodies studied except pertussis (0.753), both considering hematocrit before sample elution or not. The correlation between DBSs and plasma for diphtheria and tetanus remained strong following a 4-month delay in DBS processing at 4 °C (0.925–0.964) and −20 °C (0.924–0.966), with only a minor decrease observed for diphtheria at room temperature (0.889), while maintaining a strong correlation for tetanus (0.960). For pertussis, the correlation between DBSs and plasma was drastically reduced after delaying its processing for 4 months at any temperature. Conclusions: To summarize, hematocrit levels within the normal range do not affect the processing of DBSs in the study of serological markers of diphtheria, tetanus, and pertussis. The DBS stability for serological diagnosis of diphtheria and tetanus is adequate when samples are stored at −20 °C for a period of 4 months. The pertussis serological marker does not appear to remain stable after 4 months, even when the DBS is stored frozen at −20 °C. Full article

Hematopoietic stem cell transplant (HSCT) is now recognized as a standard treatment option for people with HIV (PWH) who develop high-risk hematologic malignancies. However, the involved polypharmacy can lead to complications from drug interactions and toxicities, affecting the efficacy and safety of chemotherapy and antiretroviral therapy (ART). Managing these patients requires a personalized approach, including the careful selection of ART based on previous therapies and potential interactions, alongside risk assessment for infections. This discussion will address the history of HSCT in PWH and management considerations for this group. Full article

Background. People living with HIV (PWH) frequently have co-morbid substance use disorders that may have been impacted by the COVID-19 pandemic. This study examined associations between COVID-related stress and increased substance use among PWH in Washington State. Methods. Between August 2020 and March 2021, we conducted an online survey of 397 PWH in western Washington. Logistic regression was used to analyze associations between a COVID-19 stress score and four self-reported outcomes: increased alcohol use, increased cigarette smoking, increased marijuana use, and increased use of illicit substances. Results. Thirty-five (38.0%) of 92 participants who smoked, 61 (23.4%) of 261 participants who used alcohol, 15 (14.6%) of 103 participants who used marijuana, and 35 (33.0%) of 102 participants who used illicit substances reported increased use of these substances. Higher COVID-19 stress scores were associated with higher odds of increased cigarette smoking (adjusted odds ratio [aOR] = 1.15, 95% confidence interval [CI]: 1.04–1.27), even after adjustment for anxiety and depressive symptoms (aOR 1.14, 95%CI: 1.03–1.27). COVID-19 stress was not associated with an increased use of alcohol, marijuana, or illicit substances. Conclusions. COVID-19-related stress was associated with self-reported increased cigarette smoking among PWH in western Washington during the pandemic. Full article

Background/Objectives: The Elecsys^® HCV Duo immunoassay (Roche Diagnostics International Ltd., Rotkreuz, Switzerland) detects both antibodies to hepatitis C virus (anti-HCV) and HCV core antigen (HCV-Ag) and has shown excellent diagnostic performance in blood donor samples. We aim to validate its use for diagnosing chronic HCV infection and assessing sustained virological response (SVR) post-direct-acting antivirals (DAAs) in patients with or without HIV infection. Methods: Blood samples from 100 healthy controls, as well as 64 HCV mono-infection and 136 HCV-HIV coinfections, were collected before and 12–24 weeks after DAAs. The assay performance for determining active infection at baseline and SVR was compared with HCV RNA. Results: Overall, 156 (78.0%) of HCV-infected patients had HCV genotype 1, and the SVR rate was 96.5%. The sensitivity, specificity, and area under the ROC curve (AUROC) for HCV diagnosis at baseline were 99.50% (95% confidence interval [CI], 96.82–99.97%), 100% (95%CI, 95.39–100%), and 0.998 (95%CI, 0.992–1.003), respectively. The corresponding results for HCV-Ag in determining SVR were 57.14% (95%CI, 20.24–88.19%), 97.41% (95%CI, 93.73–99.04%), and 0.773 (95%CI, 0.543–1.003), respectively. The assay also exhibited comparable sensitivity and specificity between HCV mono- and coinfection. Conclusions: Our study showed that the Elecsys^® HCV Duo immunoassay effectively diagnosed HCV infection, regardless of HIV status, making it suitable for managing high-risk populations in resource-limited settings. Full article

Although South Africa was the first country to register and roll out oral pre-exposure prophylaxis (PrEP) biomedical human immunodeficiency virus (HIV) prevention intervention in sub-Saharan Africa (SSA), its uptake remains low, particularly among adolescent girls and young women (AGYW). The uptake of PrEP may have worsened during the Coronavirus disease 2019 (COVID-19) pandemic. Some innovative interventions to improve PrEP uptake among AGYW have been implemented. This study aims to evaluate the effectiveness of PrEP innovative interventions implemented during COVID-19 towards reducing the risk of HIV infection among AGYW in South Africa. An exploratory, descriptive design will be conducted to carry out four study objectives. Firstly, to carry out a systematic review of innovative PrEP interventions implemented during COVID-19 in SSA countries. Secondly, to conduct a stakeholder analysis to identify PrEP stakeholders and interview them on their views on the implemented interventions. Thirdly, to assess the implementation outcomes of the innovative interventions using document reviews and Consolidated Framework for Implementation Research. Fourthly, to develop a framework for an improved PrEP service delivery among AGYW. Qualitative data will be captured in ATLAS.ti software (Technical University, Berlin, Germany) version 23 and analysed via thematic analysis. A statistical software package (STATA) version 18 (College Station, TX, USA) will be used to capture quantitative data and analyse them via descriptive analysis. The generated evidence will be used towards the development of framework, guidelines, and policies to strengthen the uptake of, scale-up, and adherence to PrEP among AGYW. Full article

Signatures of neurodegeneration in clinical samples from a subject with multiple sclerosis (MS) acutely infected with HIV were investigated with single-cell transcriptomics using 10X Chromium technology. Sequencing was carried out on NovaSeq-TM, and the analysis was performed with Cell Ranger software (v 7.1.0) associated with a specifically established bioinformatic pipeline. A total of 1446 single-cell transcriptomes in cerebrospinal fluid (CSF) and 4647 in peripheral blood mononuclear cells (PBMCs) were obtained. In the CSF, many T-cell lymphocytes with an enriched amount of plasma cells and plasmacytoid dendritic (pDC) cells, as compared to the PBMCs, were detected. An unsupervised cluster analysis, putting together our patient transcriptomes with those of a publicly available MS scRNA-seq dataset, showed up-regulated microglial neurodegenerative gene expression in four clusters, two of which included our subject’s transcriptomes. A few HIV-1 transcripts were found only in the CD4 central memory T-cells of the CSF compartment, mapping to the gag-pol, vpu, and env regions. Our data, which describe the signs of neurodegenerative gene expression in a very peculiar clinical situation, did not distinguish the cause between multiple sclerosis and HIV infection, but they can give a glimpse of the high degree of resolution that may be obtained by the single-cell transcriptomic approach. Full article

Retroviral assembly is a highly coordinated step in the replication cycle. The process is initiated when the newly synthesized Gag and Gag-Pol polyproteins are directed to the inner leaflet of the plasma membrane (PM), where they facilitate the budding and release of immature viral particles. Extensive research over the years has provided crucial insights into the molecular determinants of this assembly step. It is established that Gag targeting and binding to the PM is mediated by interactions of the matrix (MA) domain and acidic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂). This binding event, along with binding to viral RNA, initiates oligomerization of Gag on the PM, a process mediated by the capsid (CA) domain. Much of the previous studies have focused on human immunodeficiency virus type 1 (HIV-1). Although the general steps of retroviral replication are consistent across different retroviruses, comparative studies revealed notable differences in the structure and function of viral components. In this review, we present recent findings on the assembly mechanisms of Human T-cell leukemia virus type 1 and highlight key differences from HIV-1, focusing particularly on the molecular determinants of Gag–PM interactions and CA assembly. Full article

The beginning of the COVID-19 pandemic was marked by a sharp decline in syphilis infections in many countries worldwide, including Greece. However, a resurgence of positive cases started to appear in the second half of 2020. The aim of this study was to explore the impact of the pandemic on the incidence of new syphilis infections and reinfections and analyze the sociodemographic characteristics associated with recurrent episodes. We analyzed medical records from a 14-month period after the beginning of the pandemic and compared them with the respective period before the start of the pandemic. Our participants consisted mainly of men, with a median age of 43 years, homosexual orientation, and higher education. During COVID-19, more HIV patients presented for syphilis testing (38.0% vs. 34.6%, p = 0.025). Overall, we observed almost a two-fold increase in positive syphilis cases during COVID-19 (21.1% vs. 12.4%, p < 0.001), with new infections rising from 8.4% to 13.2% and reinfections from 4.0% to 7.9%. Multivariable logistic regression analysis revealed that the COVID-19 pandemic, among different parameters (such as age, gender, sexual orientation, HIV status, and educational level), was the only factor associated with higher positive syphilis rates (OR 1.47, 95% CI: 1.07–2.01, p = 0.003). Our results highlight the need to ensure enhanced prevention and undisrupted healthcare services, with a focus on future pandemics. Full article

In Zimbabwe, artisanal and small-scale miners (ASMs) are a key vulnerable group with high risk for tuberculosis (TB), HIV, and silicosis. The main purpose of this study was to investigate treatment outcomes of TB among ASMs. We conducted a follow-up observational study using secondary data. We analyzed data from 208 ASMs treated for TB at two occupational health clinics. We found a high treatment success rate of 87%, comparable to the national average for drug-sensitive TB. Unsuccessful outcomes were due to death (5%) and loss to follow-up (7%). Over a quarter of ASMs had unknown HIV status. Our study is the first to document treatment outcomes of TB among ASMs in Zimbabwe. Encouragingly, this study demonstrates the possibility of achieving good TB treatment outcomes even among highly mobile populations like ASMs. Further research is needed to analyze leakages across the whole TB patient pathway among ASMs. Additionally, addressing the high rate of unknown HIV statuses among ASMs is crucial to further improve overall TB treatment outcomes in this population. Full article

Cervical cancer (CC) remains a prevalent malignancy and a significant global public health concern, primarily driven by persistent human papillomavirus (HPV) infections. The infectious nature of HPV underscores the preventability of CC through vaccination and screening programs. In addition to HPV, factors such as age, parity, smoking, hormonal contraceptives, and HIV co-infection elevate the risk of CC. HIV-associated immunodeficiency exacerbates susceptibility to infections and cancers, making CC a defining condition for acquired immune deficiency syndrome (AIDS) and one of the most commonly diagnosed cancers among women living with HIV (WLWH). These women face higher risks of HPV exposure due to sexual behavior and often encounter economic, social, and psychological barriers to screening. HIV and HPV co-infection can potentially accelerate CC carcinogenesis, with WLWH typically being diagnosed with CC earlier than their HIV-negative counterparts. Antiretroviral therapy (ART), which reduces AIDS-related mortality, also lowers the risk of invasive CC. The interaction between HIV and HPV is intricate and bidirectional. This summary reviews current evidence on HPV infection and CC in WLWH, highlighting the connections across pathogenesis, prevention, diagnosis, and treatment. Full article