Search Results (216)

Background: Adolescent girls and young women (AGYW) who engage in alcohol and substance abuse face more significant health and social consequences compared to the general population. This study evaluated the prevalence and associated factors of alcohol abuse and substance use among AGYW in Namibia. Methods: We conducted a retrospective analysis of programmatic data from AGYW aged 10–24 who participated in the Determined, Resilient, Empowered AIDS-free, Mentored, and Safe (DREAMS) component of the Reducing HIV Vulnerability: Integrated Child and Youth Health (REACH) Project HOPE Namibia from March to December 2024. Data analysis was conducted employing chi-squared tests alongside binomial and multinomial logistic regression. Results: Among the 19,662 participants included in this analysis, 2068 (10.5%) abused alcohol and/or substances in the previous six months. Participants who were HIV-negative or did not know their status (AOR = 1.57, 95% CI (1.15–2.14), and AOR = 1.50, 95% CI (109–2.07), respectively), from outside Windhoek, those who had failed or repeated school in the previous year (COR = 1.77, 95% CI (1.54–2.05)), those not disabled (AOR = 1.27, 95% CI (1.06–1.52)), those who had dropped out of school or had completed their studies, and those with no adult emotional support (AOR = 1.25, 95% CI (1.11–1.40)), were more likely to have abused alcohol and/or substances recently. In contrast, participants who were not depressed were less likely to have recently abused alcohol and substances. Conclusions: The prioritization of strategies to identify AGYW experiencing depression and to provide them with treatment is essential. Moreover, it is important to encourage parents and guardians to provide emotional support to AGYW, as it prevents them from abusing alcohol and substances. Full article

Human immunodeficiency virus (HIV) continues to be a threat to public health. An emerging technique with promise in the context of fighting HIV type 1 (HIV-1) focuses on targeting ribosomal frameshifting. A crucial –1 programmed ribosomal frameshift (PRF) has been observed in several pathogenic viruses, including HIV-1. Altered folds of the HIV-1 RNA frameshift element (FSE) have been shown to alter frameshifting efficiency. Here, we use RNA-As-Graphs (RAG), a graph-theory based framework for representing and analyzing RNA secondary structures, to perform conformational analysis in motif space to propose how sequence length may influence folding patterns. This combined analysis, along with all-atom modeling and experimental testing of our designed mutants, has already proven valuable for the SARS-CoV-2 FSE. As a first step to launching the same computational/experimental approach for HIV-1, we compare prior experiments and perform SHAPE-guided 2D-fold predictions for the HIV-1 FSE embedded in increasing sequence contexts and predict structure-altering mutations. We find a highly stable upper stem and highly flexible lower stem for the core FSE, with a three-way junction connecting to other motifs at increasing lengths. In particular, we find little support for a pseudoknot or triplex interaction in the core FSE, although pseudoknots can form separately as a connective motif at longer sequences. We also identify sensitive residues in the upper stem and central loop that, when minimally mutated, alter the core stem loop folding. These insights into the FSE fold and structure-altering mutations can be further pursued by all-atom simulations and experimental testing to advance the mechanistic understanding and therapeutic strategies for HIV-1. Full article

Hepatitis C virus (HCV) remains a global health challenge, contributing to chronic liver disease and hepatocellular carcinoma. In Thailand, HCV prevalence has declined from ~2% in the 1990s due to universal blood screening, harm reduction, and expanded treatment. This narrative review draws on diverse sources—including PubMed and Scopus databases, international and national health websites, government reports, and local communications—to compile epidemiological data, genotype distribution, and elimination strategies, with a focus on Phetchabun province, Thailand, as a model for achieving the World Health Organization’s (WHO) hepatitis C elimination targets. National surveys in 2004, 2014, and 2024 show a prevalence drop from 2.15% to 0.56%. However, HCV persists among high-risk groups, including people who inject drugs, people living with HIV, patients undergoing maintenance hemodialysis, and prisoners. Thailand’s National Health Security Office has expanded treatment access, including universal screening for those born before 1992. The Phetchabun Model, launched in 2017, employs a decentralized test-to-treat strategy. By April 2024, 88.64% (288,203/324,916) of the target population was screened, and 4.88% were anti-HCV positive. Among those tested, 72.61% were HCV-RNA positive, and 88.17% received direct-acting antivirals (i.e., SOF/VEL), achieving >96% sustained virological response. The Phetchabun Model demonstrates a scalable approach for HCV elimination. Addressing testing costs, improving access, and integrating microelimination strategies into national policy are essential to achieving the WHO’s 2030 goals. Full article

In 2022, scientific societies agreed on a document with recommendations for a comprehensive diagnosis of viral hepatitis (B, C, and D). The aim was to evaluate the situation in Spain regarding the comprehensive diagnosis of viral hepatitis in a single blood draw before it is recommended. A panel of experts prepared a structured survey directed at hospitals (public or private with teaching accreditation) with ≥200 beds (sent 20 October 2022, closed 1 December 2022). The response rate was 61% (79/129; 52 hospitals with >500 beds). Among the participating hospitals, all could perform tests for HBsAg, anti-HCV, and HIV serology; 94% could perform PCR testing for HCV, 63% could test for anti-HDV, and 28% could test for HDV-RNA (67% [53/79] outsourced this testing). Point-of-care (POC) testing availability was low (24%), with 84% of these tests being supervised by the reference microbiological laboratory and the results being registered in the patients’ medical history. Ninety percent of the centers carried out the diagnosis in a single step (99% HCV, 70% HBV, 48% HDV, and 44% HBV-HDV). In addition, 77% used some communication strategy when an active infection was encountered (100% HCV, 49% HBV, and 31% HDV). Only 20% had an automated system for scheduling a specialist physician appointment. Most hospitals had the means for a comprehensive diagnosis of viral hepatitis in a single sample, but <50% could test for HBV/HDV. Alerts for continuity of care were available for HCV, but not HBV or HDV. POC device implementation is important for decentralized testing. Full article

Background/Objectives: Extrapulmonary tuberculosis accounts for a significant portion of tuberculosis cases, presenting unique diagnostic challenges due to its heterogeneous manifestations and paucibacillary nature. This study aims to fill this gap by evaluating the diagnostic outcomes and correlations between different specimen types and test results. Methods: A retrospective analysis of electronic medical records of patients diagnosed with TB between January 2013 and December 2023 was carried out. The data extracted included patient demographics, comorbidities, TB classification, specimen types, microbiological test results, and time intervals to diagnosis. Statistical analysis was applied to compare the variables between pulmonary and extrapulmonary/disseminated TB groups. Results: Most patients were male (62.4%) and born outside of Germany (74.2%). Comorbidities, such as diabetes, cardiac disease, immunosuppressed status, and HIV, were common. Among the 194 patients, 98 had pulmonary TB, and 96 had extrapulmonary/disseminated TB. A comparison of pulmonary vs. extrapulmonary TB showed that extrapulmonary TB patients had a longer diagnostic delay (p = 0.013), more symptoms (p = 0.001), and more complications (42.7% vs. 16.3%, p < 0.001). Diagnostic challenges were evident, with multiple invasive procedures required in 43.5% of the extrapulmonary TB cases. Conclusions: This study highlights the complex clinical presentation of tuberculosis, particularly in patients with extrapulmonary and disseminated forms, who experience delayed diagnosis and more complications. These challenges in diagnosing extrapulmonary TB emphasize the need for improved diagnostic strategies and early identification, especially in high-risk populations. Full article

This study aimed to assess the prevalence of HDV (hepatitis delta virus), HCV (hepatitis C virus), and HIV (human immunodeficiency virus) coinfections among HBsAg-positive patients and to determine the severity of liver fibrosis and biochemical markers. Furthermore, the study sought to evaluate the noninvasive fibrosis scores (APRI and FIB4) in predicting the severity of liver disease in patients with hepatitis B. A retrospective analysis of 1434 patients with chronic HBV admitted between January 2020 and December 2024 was conducted at Sincan Tertiary Hospital. The positivity rates of the following antibodies were the focus of the study: anti-HDV, anti-HCV, and anti-HIV. In addition to these, the levels of HIV-RNA, HCV-RNA and HBV-DNA, as well as several biochemical markers (ALT, AST, INR, albumin, bilirubin and platelet count) were also evaluated. The APRI and FIB-4 scores were calculated. Of the 1434 patients, 49 (3.4%) tested positive for anti-HDV, 784 were screened for anti-HCV, and 749 were screened for anti-HIV. The positivity rates were 3.4% (27/784) and 3.4% (26/749), respectively. According to ROC analysis, the FIB-4 score had a statistically significant effect on predicting anti-HDV negativity (AUC = 0.59, p = 0.031). However, the APRI score was not a significant predictor for anti-HDV positivity (AUC = 0.53, p > 0.05). APRI and FIB-4 scores did not have a statistically significant discriminatory power in predicting anti-HCV and anti-HIV positivity (p > 0.05). The cut-off value for the FIB-4 score in predicting anti-HDV positivity was 1.72, with a sensitivity of 61.4% and a specificity of 42.9% (p = 0.031). Among the HCV/RNA-positive patients (n = 5), all were male, and two also had positive anti-HBe results with undetectable HBV/DNA levels. One HIV/RNA-positive patient, a foreign national, was confirmed to have HIV/HBV/HDV infection. All HBsAg-positive patients should undergo routine anti-HDV testing. Vaccination programmes are vital in preventing the spread of HDV. Dual screening strategies are essential for identifying infected individuals and developing prevention and treatment programmes. Anti-HDV positivity indicates advanced liver fibrosis, emphasising the importance of screening and monitoring. However, the limited accuracy of the APRI and FIB-4 scores for detecting coinfections highlights the need to integrate noninvasive methods with molecular diagnostics for precise management. Full article

HIV-1 genotyping and drug resistance tests are routinely performed in virology laboratories in some countries, aiding clinical management. In Istanbul, between January 2021 and March 2024, plasma samples from 1029 HIV-1-infected patients were analyzed using the NGS method, and mutation and drug resistance results were retrospectively evaluated alongside demographic data. Subtype B (54.4%) was most frequent in Turkish patients, while Subtype A1 (43.5%) was predominant among foreign nationals. The most common CRFs were CRF02_AG (3.8%) and CRF56_cpx (1.6%). According to the change in detection rates during the study period, Subtype B decreased, and Subtype A increased. The most frequent mutations detected were A62V (38.7%) and M184V (22.4%) for NRTIs; E138A (55.5%) and E138G (11.5%) for NNRTIs; M46I (33.3%) and M46L (25%) for PIs; and E92Q and G for INIs (total rate: 35.2%). Darunavir/ritonavir had the highest sensitivity rate, while resistance rates for NNRTIs and INIs increased over time. We anticipate that this study, in which we evaluate the routine use of an FDA-approved NGS kit alongside integrated bioinformatics data analysis and automated reporting software for the first time in Türkiye, will contribute to both national and international molecular epidemiological data and public health strategies by providing reliable results that align with international standarts. Full article

Background/Objectives: Squamous cell carcinoma of the anus (SCCA) remains a relatively rare form of cancer linked to high-risk human papillomavirus (HR-HPV) infection; however, its incidence has been increasing globally. Anal cytology and HR-HPV testing can identify precursors, though standardized screening guidelines are still lacking. This study aimed to assess the correlation between high-resolution anoscopy (HRA) findings and primary screening results through PAP-HPV co-testing in high-risk patients. Methods: A retrospective, single-center study was conducted collecting data from the joint multidisciplinary anal cancer clinic of Piero Palagi Hospital in Florence (Italy), between August 2019 and September 2022. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of anal cytology, HR-HPV testing, and PAP-HPV co-testing were assessed. Results: In 577 HRAs, histology revealed 31 AIN2+ lesions (5.4%) and 220 AIN1 lesions (38.1%), while 326 (56.5%) were negative. Cytology alone showed a sensitivity of 74.2% and specificity of 63.3% for AIN2+ lesions, while HR-HPV testing alone had a sensitivity of 96.8% and specificity of 38.1%. Co-testing demonstrated 100% sensitivity and a 100% NPV for AIN2+ lesions. Among men who have sex with men (MSM), no significant differences in outcomes were observed between HIV-positive and HIV-negative patients, likely reflecting similar high-risk behaviors and effective HIV treatments. Conclusions: Co-testing with anal cytology and HR-HPV testing provides the most reliable screening for high-grade lesions (AIN2+), surpassing the reliability of individual methods. Tailored co-testing strategies are crucial for early detection and effective prevention in high-risk groups. Full article

Latent tuberculosis infection (LTBI) poses a significant public health challenge, especially in populations with high HIV prevalence and limited healthcare access. Early detection and targeted interventions are essential to prevent the progression of active tuberculosis. This study aimed to identify the key factors influencing LTBI outcomes through the application of predictive models, including logistic regression and machine learning techniques, while also evaluating strategies to enhance LTBI awareness and testing. Data from rural areas in the Eastern Cape, South Africa, were analyzed to identify key demographic, health, and knowledge-related factors influencing LTBI outcomes. Predictive models utilized, included logistic regression, decision trees, and random forests, to identify key determinants of LTBI positivity based on demographic, health, and knowledge-related factors in rural areas of the Eastern Cape, South Africa. The models evaluated factors such as age, HIV status, and LTBI awareness, with random forests demonstrating the best balance of accuracy and interpretability. Additionally, a knowledge diffusion model was employed to assess the effectiveness of educational strategies in increasing LTBI awareness and testing uptake. Logistic regression achieved an accuracy of 68% with high precision (70%) but low recall (33%) for LTBI-positive cases, identifying age, HIV status, and LTBI awareness as significant predictors. The random forest model outperformed logistic regression in accuracy (59.26%) and F1-score (0.63), providing a better balance between precision and recall. Feature importance analysis revealed that age, occupation, and knowledge of LTBI symptoms were the most critical factors across both models. The knowledge diffusion model demonstrated that targeted interventions significantly increased LTBI awareness and testing, particularly in high-risk groups. While logistic regression offers more interpretable results for public health interventions, machine learning models like random forests provide enhanced predictive power by capturing complex relationships between demographics and health factors. These findings highlight the need for targeted educational campaigns and increased LTBI testing in high-risk populations, particularly those with limited awareness of LTBI symptoms. Full article

HIV testing is crucial towards the control of the Acquired Immune Deficiency Syndrome (AIDS) epidemic. Monitoring trends of human immunodeficiency virus (HIV) testing over time may help interpret the incidence of new HIV diagnoses and effectiveness of HIV testing strategies. We started a research project aimed at assessing testing rates for HIV infection among Italian outpatients in 2018–2023. Numeric data for screening, confirmatory, and monitoring tests obtained by a national register were compared with the numbers of adult residents, newly diagnosed HIV infections, and patients undergoing treatment. The number of screening tests declined from 1,133,377 in 2018 to 889,972 in 2020 and increased to 1,096,822 in 2023. HIV-RNA tests showed a similar pattern, whereas confirmatory immunoblots did not vary significantly over time. The ratio of screening tests to adult residents was higher in North-West (2.87%) and North-East (2.31%) Italy compared to South Italy and the islands (1.47%), indicating that screening should be enhanced in the latter area. We observed differences between the ratio of screening tests and the incidence of newly diagnosed HIV infections by geographic area. Discrepancies in the number of screening and confirmatory tests needed for each new diagnosis suggest repeated testing on people already diagnosed and possible data reporting issues. The monitoring of HIV screening tests at the national and regional levels can provide essential data to interpret trends in HIV epidemiology and plan relevant testing strategies over time. Full article

Papillomaviruses are double-stranded DNA viruses, and it is essential to clarify their genotypic distribution for their effective prevention and clinical management. In this study, we aimed to evaluate the prevalence of HPV genotypes in the normal oral mucosae of HIV-positive individuals. A systematic literature search was conducted across PubMed, Web of Science, Scopus, and Google Scholar to identify peer-reviewed studies published up to 13 February 2025. The inclusion criteria referred to original research studies reporting on the prevalence and genotype-specific distribution of HPV in the oral mucosae of HIV-positive individuals. Statistical analyses were conducted using the MedicReS E-PICOS AI smart biostatistics software (version 21.3, New York, NY, USA) and the MedCalc statistical software package (MedCalc Software Ltd., Ostend, Belgium). The pooled prevalence estimates were calculated using a random-effects meta-analysis model, and heterogeneity was quantified using the Cochrane Q and I² statistics. The presence of publication bias was assessed via the Begg and Mazumdar rank correlation test. High prevalence and heterogeneity of HPV-58 (6.23%), HPV-16 (4.326%), and HPV-66 (3.733%) were observed, indicating significant variability across populations and methodologies. This supports their association with HPV-related oropharyngeal malignancies and the need for the continuous surveillance of HIV-positive individuals. We also observed the elevated detection of LR-HPV genotypes, particularly HPV-13 (7.16%), HPV-5 (5.64%), and HPV-62 (4.24%). These findings indicate that there is substantial heterogeneity in the prevalence of both HR-HPV and LR-HPV genotypes among HIV-positive individuals, with certain genotypes exhibiting higher detection rates across studies, emphasizing the need for targeted surveillance and preventive strategies in this vulnerable population. The application of advanced data analysis methods is essential in enhancing HPV surveillance and implementing effective control measures in this vulnerable population. Full article

Background/Objectives: The development of an effective HIV vaccine has faced persistent challenges, as evidenced by the recent discontinuation of the Mosaico phase 3 trial. This study aims to critically examine the obstacles encountered in HIV vaccine development, with a focus on the Mosaico trial, which tested the Ad26.Mos4.HIV vaccine among 3,900 participants across multiple countries. We also explore emerging vaccine technologies and their potential in overcoming these challenges, while reflecting on lessons from previous trials to inform future strategies. Methods: We reviewed the Mosaico trial’s approach, which involved testing the efficacy of the Ad26.Mos4.HIV vaccine. We compared the outcomes of the Mosaico trial with other major HIV vaccine trials, including HVTN 702, Imbokodo, and RV144. We explored the limitations of the immune responses elicited by the Mosaico vaccine. The review focused on the generation of broadly neutralizing antibodies (bNAbs) and the challenges related to antigenic diversity and B-cell engagement. Emerging vaccine technologies, such as virus-like particles (VLPs), nanoparticles, SOSIP trimers, and mRNA platforms, were also analysed for their scalability, immune durability, and potential to advance HIV vaccine development. Results: The Mosaico trial was discontinued due to insufficient efficacy in reducing HIV acquisition, primarily due to the inability of the vaccine to induce bNAbs, which are crucial for targeting the diverse HIV-1 strains. A major challenge was the inadequate engagement of germline B-cell precursors, compounded by the antigenic diversity of the virus. The analysis showed that emerging vaccine platforms, such as VLPs, nanoparticles, SOSIP trimers, and mRNA-based approaches, hold promise but present challenges related to scalability and the durability of immune responses. The role of T cells and adjuvants in enhancing vaccine efficacy was also highlighted as critical for integrating both humoral and cellular immunity. Conclusions: The Mosaico trial, as well as other major HIV vaccine trials, underscores the need for a multi-pronged approach that incorporates both antibody and T-cell responses to tackle the complexities of HIV-1. Future efforts in HIV vaccine development must focus on inducing bNAbs, generating robust T-cell responses, and utilizing scalable vaccine platforms. The integration of artificial intelligence (AI) into vaccine design offers new opportunities to optimize immunogenic targets, which could significantly improve the potential for durable and broad immune protection. The development of a successful HIV vaccine by 2030 is achievable but relies on leverage on advanced technologies including artificial intelligence, innovation and insights from past trial data. Full article

Acute HIV-1 infection (AHI) is a transient period where the virus causes evident damage to the immune system, including an extensive apoptosis of CD4+ T cells associated with a high level of activation and a major cytokine storm to fight the invading virus. HIV infection establishes persistence by integrating the viral genome into host cell DNA in both replicating and non-replicating forms, effectively hiding from immune surveillance within infected lymphocytes as cellular reservoirs. The measurement of total HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) is a reliable reflection of this reservoir. Initiating treatments during AHI with nucleoside reverse transcriptase inhibitors (NRTIs) and/or integrase strand transfer inhibitors (INSTIs) is essential to alter the dynamics of the global reservoir expansion, and to reduce the establishment of long-lived cellular and tissue reservoirs, while preserving and enhancing specific and non-specific immune responses. Furthermore, some of the patients treated at the AHI stage may become post-treatment controllers and should be informative regarding the mechanism of viral control, so patients treated during AHI are undoubtedly the best candidates to test innovative remission strategies toward a functional cure that could play a pivotal role in long-term HIV control. AHI is characterized by high levels of viral replication, with a significant increase in the risk of HIV transmission. Detecting AHI and initiating early treatment following diagnosis provides a window of opportunity to control the epidemic, particularly in high-risk populations. Full article

HIV-1 infection cannot be cured due to the presence of HIV-1 latently infected cells. These cells do not produce the virus, but they can resume virus production at any time in the absence of antiretroviral therapy. Therefore, people living with HIV (PLWH) need to take lifelong therapy. Strategies have been coined to eradicate the viral reservoir by reactivating HIV-1 latently infected cells and subsequently killing them. Various latency reversing agents (LRAs) that can reactivate HIV-1 in vitro and ex vivo have been identified. The most potent LRAs also strongly activate T cells and therefore cannot be applied in vivo. Many LRAs that reactivate HIV in the absence of general T cell activation have been identified and have been tested in clinical trials. Although some LRAs could reduce the reservoir size in clinical trials, so far, they have failed to eradicate the reservoir. More recently, immune modulators have been applied in PLWH, and the first results seem to indicate that these may reduce the reservoir and possibly improve immunological control after therapy interruption. Potentially, combinations of LRAs and immune modulators could reduce the reservoir size, and in the future, immunological control may enable PLWH to live without developing HIV-related disease in the absence of therapy. Full article

Contemporary ART as Dolutegravir (DTG) has significantly advanced antiretroviral therapy, but relatively few data are available on its impact on the emergence of HIV-1 drug resistance mutations (DRMs). Monitoring the emergence of INSTI-associated DRMs following the introduction of DTG in Suriname will provide general insight and guide national HIV treatment strategies. All people living with HIV (PLHIV) in Suriname, for whom an INSTI drug resistance test was requested between September 2019 and February 2024 (n = 20), were included. HIV-1 integrase gene sequences were determined using Sanger sequencing. INSTI-associated mutations were identified using the Stanford HIV Drug Resistance Database program. The majority of the participants (66.7%) harbored HIV-1 subtype B, and 33.3% were B-recombinant forms. In addition to the INSTI wildtype, a strain was revealed carrying E157EQ and one person harbored a highly INSTI-resistant strain (E138K, G140S, Q148H and N155H). The emergence of a highly INSTI-resistant HIV-1 strain in Suriname, with unusual mutations for ART-experienced PLHIV exposed to DTG as the only INSTI, accentuates the need for continuous monitoring of the emergence of INSTI drug resistance mutations, not only to enable timely interventions and optimized treatment outcomes for PLHIV, but also to steer the decision making for ART protocols, especially for second generation INSTIs. Full article