Search Results (1,688)

HIV-1 protease (PR) is an essential enzyme in the viral life cycle and a primary target of antiretroviral therapies, particularly protease inhibitors (PIs). Understanding the dynamics of viral evolution and the factors governing the emergence or loss of resistance-associated mutations is critical for improving PI efficacy and managing drug resistance in HIV/AIDS treatment. In this study, we investigated the impact of three natural HIV-1 polymorphisms (T12A, L63Q, and H69N), whose prevalence varies depending on treatment status and viral subtype, on the structural stability and conformational dynamics of PR using molecular dynamics (MD) simulations. Three independent 500 ns MD simulations were performed for the native protease and each mutant system. Although none of the mutations disrupts the overall structural integrity of HIV-1 PR, they induce mutation-specific alterations in flexibility and residue interactions. In particular, T12A and H69N exhibit increased structural deviations, especially in the flap regions, along with enhanced conformational fluctuations. In contrast, the L63Q mutation shows a slight reduction in flap flexibility compared to both the native protease and the other mutants. Consistently, the fraction of time spent in open-flap conformations is higher for T12A and H69N and lower for L63Q relative to the native system. Moreover, mutations in the Fulcrum (T12A) and Cantilever (L63Q and H69N) regions do not disrupt the long-range network of correlated motions observed in the native protease, both inter- and intra-monomer, but instead increase the extent of correlated and anti-correlated motions in other regions of PR. Full article

Background: Intraventricular central nervous system (CNS) lymphoma is an atypical presentation of extranodal lymphoma, whether primary or secondary. The most commonly diagnosed subtype of lymphoma is diffuse large B-cell lymphoma (DLBCL). There is a documented relation of HIV, EBV and KSHV infections with lymphomagenesis. AIDS-related lymphomas (ARLs) are described as a defining illness of the acquired immunodeficiency syndrome (AIDS). This study presents a novel case and systematic review of clinical, radiographic and histopathological features of intraventricular lymphomas. Methods: We report on a 27-year-old woman with a left lateral ventricle DLBCL with surrounding edema treated with steroids. A systematic review of 147 additional cases (1977–2025) was conducted, analyzing patient demographics, tumor characteristics, clinical features, imaging, treatment, and outcomes. The tumor locations were divided into three groups depending on the extent of ventricular involvement. Descriptive statistics summarized findings. Findings: 147 cases (mean age, 54.2 years; range, 3–87; 63.3% male) were analyzed. Immunodeficiency in patients was unusual (6.1%). Fully intraventricular lesions were the most common presentation (52.4%), with systemic involvement solely in 10 cases (6.8%). The lesions were predominantly located in the lateral ventricles or fourth ventricles (46 times each), and bilateral involvement was noted 37 additional times. DLBCL was diagnosed in 101 cases (78.9%). Interpretation: Intraventricular involvement in central nervous system lymphoma poses a diagnostic and therapeutic challenge due to non-specific symptoms and atypical locations. Adding to the diagnostic difficulty of intraventricular masses in young patients, we wish to highlight that immunocompromised patients are a notably insignificant subgroup of patients in our study. Full article

Syphilis and HIV are sexually transmitted disease (STDs) that interact synergistically. However, data on HIV–syphilis co-infection in Romania remain limited. We conducted a retrospective cohort study at a single Romanian HIV/AIDS Day Clinic, including 439 adult people living with HIV (PLWH) monitored between 2020 and 2025. Demographic, epidemiological, clinical, and laboratory data were collected, including HIV staging and syphilis history. Syphilis co-infection was identified in 81 patients (18.5%), and 61.5% met criteria for AIDS. Viral suppression was achieved in 82.2%, and 78.4% achieved CD4 counts >350 cells/mm³. Male sex, urban residence, unmarried status, sexual HIV transmission, genital condyloma, and other STIs were independently associated with syphilis. First episodes of syphilis were predominantly secondary (61%), neurosyphilis was present in 5%, and serofast evolution occurred in 12%, more frequently after reinfection. Among deceased patients, 20.9% had a history of syphilis, but co-infection was not significantly associated with mortality. Nine of 28 patients lost to follow-up had prior syphilis, suggesting a potential impact on retention in care. These findings indicate that HIV–syphilis co-infection is increasingly prevalent in Romania, driven primarily by behavioral factors, and highlight the need for targeted STD screening and prevention strategies among high-risk PLWH. Full article

Background: Miami-Dade County ranks first in Florida for HIV cases, yet broad epidemiological data often masks the “on-the-ground” reality of its most vulnerable residents. While standard reports suggest declining domestic violence, these statistics fail to account for community-defined health crises—the “SAVA” syndemic (substance use, violence, and HIV/AIDS)—occurring within localized micro-communities. Methods: Leveraging five years of Community-Based Participatory Research (CBPR) and Grounded Theory, this study engaged 97 community members and leaders to unmask these hidden burdens. We employed a multi-level sequential design and methodological triangulation, incorporating community forums, focus groups, and interviews with farm-workers, inner-city residents, and LGBTQ+ individuals. Results: Findings reveal a disconnect between official data and community reporting, including “Party and Play” methamphetamine/sex-trafficking networks in the LGBTQ+ scene, rampant youth vaping in inner cities, and child sexual abuse and opioids in farm-working communities. Mental health emerged as a pervasive need, masked by substance use and suppressed by cultural stigmas and institutional fears. Conclusions: Findings from this study highlight the value of community-level approaches in generating localized, culturally grounded insights that may not be fully captured in more aggregated geographic analyses (e.g., zip code, county, or state levels). We propose a collaborative, multi-sectoral model to address the systemic factors underlying the SAVA syndemic in these communities. Full article

Intestinal dysbiosis is common in people living with HIV/AIDS (PLWH), yet fungal communities of the gut microbiota (mycobiota) remain poorly characterized, especially in severely immunosuppressed patients. We analyzed the gut mycobiota of 33 PLWH and 20 healthy controls from a public hospital in central Argentina. Most PLWH presented with severe immunosuppression (<200 CD4⁺ T cells/μL) and acute or chronic diarrhea, with or without antibiotic exposure or antiretroviral therapy. Fecal DNA was extracted and the ITS2 region was sequenced using next-generation sequencing. Beta-diversity analyses revealed significant segregation between PLWH and controls (PERMANOVA, Adonis: p = 0.001, R² = 0.0989). LEfSe analysis identified 17 fungal species enriched in PLWH, predominantly Candida albicans, Candida dubliniensis, and Nakaseomyces glabratus, whereas 31 species were differentially represented in controls, including Penicillium spp., Candida sake, and Clavispora lusitaniae. Histoplasma capsulatum, an endemic pathogen in the region, was more prevalent in PLWH and associated with low CD4⁺ T cell counts. Dirichlet multinomial mixture analysis revealed two mycobiotypes: M1, with a balanced fungal composition predominating in controls, and M2, dominated by Candida species and present in PLWH. These findings provide novel insights into gut mycobiota alterations in severely immunosuppressed PLWH in Argentina, highlighting Candida-driven dysbiosis and the regional relevance of H. capsulatum. Full article

Background: The full-scale Russian invasion of Ukraine in 2022 triggered the largest displacement crisis in Europe in recent decades. Displacement may affect both clinical outcomes and mental health among people living with HIV (PLHIV). Evidence comparing displaced PLHIV with host-country patients within the same healthcare system remains limited. This study aimed to compare epidemiological characteristics, clinical staging, and mental health outcomes between war-displaced Ukrainian PLHIV and Slovak PLHIV receiving care in the same clinical setting, with particular attention to sex-specific differences. Methods: This cross-sectional study included 137 PLHIV receiving care at the HIV/AIDS Centre, University Hospital Bratislava, Slovakia (69 from Ukraine and 68 from Slovakia). Anxiety and depressive symptoms were assessed using the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) scales. Scores were categorized into three severity groups (0–4, 5–9, ≥10). Results: Age distribution was comparable between cohorts (p = 0.2438). Transmission patterns differed substantially: heterosexual transmission predominated among Ukrainian participants, whereas men who have sex with men (MSM) transmission predominated among Slovak men (p < 0.001). Ukrainian patients were more frequently classified in CDC stage C, while Slovak patients more often presented in stage A. The combined antiretroviral therapy coverage was 100% in both cohorts and viral suppression rates were high (HIV RNA < 200 copies/mL: 91.3% in Ukraine vs. 94.1% in Slovakia). Overall anxiety and depressive symptom severity did not differ significantly between cohorts (GAD-7 p = 0.4145; PHQ-9 p = 0.7661). However, within the Ukrainian cohort, women demonstrated higher depressive symptom severity compared with men (p = 0.0478). Conclusions: War-displaced Ukrainian PLHIV achieved comparable biomedical outcomes to host-country patients within a structured healthcare system. However, depressive vulnerability emerged at the intersection of gender and displacement. These findings highlight the importance of integrating gender-sensitive mental health screening and psychosocial support into routine HIV care for displaced populations. Full article

People with HIV (PWH) may exhibit altered immune responses to SARS-CoV-2 vaccination due to persistent immune dysregulation despite antiretroviral therapy. We evaluated humoral immunogenicity following mRNA SARS-CoV-2 vaccination in PWH according to CD4 T-cell count and compared responses with HIV-negative controls. The study included 57 PWH stratified by CD4 count (<200 and ≥200 cells/µL), alongside 12 HIV-negative controls. Neutralizing antibody titers (NT50) against SARS-CoV-2 pseudoviruses expressing the D614G and Omicron BA.5 spike variants were measured using a luciferase-based neutralization assay one month (M1) and six months (M6) after primary vaccination with BNT162b2 or mRNA-1273. PWH with CD4 counts ≥ 200 cells/µL demonstrated higher neutralizing titers against D614G at M1 and M6, with significant differences observed between CD4 groups (M1: p = 0.03; M6: p = 0.02). Neutralization of BA.5 was lower overall; while no overall group differences were observed at M1, higher titers were detected among individuals with CD4 ≥ 200 cells/µL at six months (p = 0.04). Neutralizing titers correlated positively with CD4 counts among PWH. Responses were broadly comparable between PWH and HIV-negative controls and did not differ substantially by vaccine type. These findings indicate that immune status, reflected by CD4 T-cell count, is a key determinant of SARS-CoV-2 vaccine-induced humoral responses in PWH and support prioritizing vaccination strategies for individuals with advanced immunosuppression. Full article

Antiretroviral therapy (ART) effectively controls Human Immunodeficiency Virus Type-1 (HIV-1) infection in people with HIV-1 (PWH), preventing the progression of their infections to AIDS. However, as PWH age, they experience lifestyle- and age-related diseases, notably various types of cancer beyond those traditionally associated with AIDS, with greater incidence and mortality than their non-HIV-1-positive counterparts, despite effective arrest of HIV-1 infection by ART. Dysregulation of redox enzymes presents an underexplored linkage between HIV-1 infection and cancer comorbidity, impacting reactive oxygen/nitrogen species (RONS) management, inflammation, immune function, and mitochondrial function. Chronic HIV-1 infection increases both RONS production and RONS neutralization responses, accelerating development of a sustained RONS-rich environment that still possesses sufficient dampening to prevent outright cytotoxic effects. Such an environment promotes both tumor proliferation and resistance adaptations to chemo- and radiotherapies. This review considers the effects of chronic HIV-1 infection on redox enzyme function and links these effects to tumorigenic mechanisms as potentially shared pathways. We then examine current methods of modulating redox function, consider how these could potentially impact both HIV-1 infection and cancer progression, and lastly propose future methods of co-treatment that could be explored. Full article

We conducted a PRISMA-guided systematic review to summarize recent methodological advances in joint modeling. A PubMed search for English-language, peer-reviewed, full-text available articles published between 1 January 2019 and 30 January 2025 was conducted using the keywords “joint model”, “joint modeling”, “longitudinal and survival”, “longitudinal and time-to-event”, and “public health”, resulting in 70 methodological studies from 793 records after screening. Original studies proposing methodological innovations in joint modeling were eligible, while clinical applications, reviews, comparative or predictive studies, and articles without full text were excluded. The reviewed methods introduced advances in both longitudinal and/or survival sub-models, including generalized linear mixed models, functional or latent class approaches, and flexible survival models, such as frailty, accelerated failure time, B-spline, and competing risks models. In total, 49% of the studies focused on longitudinal sub-model adaptations. This review is subject to limitations, including potential omission of relevant studies due to database, search term, and language restrictions. These developments have enhanced the flexibility of joint models for analyzing complex data structures, particularly in cardiovascular and oncology research, as well as broader public health applications. Despite these advances, challenges remain, including handling high-dimensional sparse data, reducing computational burden, and the lack of standardized evaluation metrics. This research received no external funding. Full article

Background: People living with HIV (PLWH) have a substantially increased risk of both AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs), which remain a major cause of morbidity despite effective antiretroviral therapy (ART); this review aims to integrate current epidemiological, molecular, and clinical evidence on HIV-associated oncogenesis. Methods: A structured literature search was conducted in PubMed (2000–2026) using predefined keywords, including “HIV”, “cancer”, “oncogenesis”, and “immune dysregulation”, with inclusion of original studies, systematic reviews, and meta-analyses meeting predefined quality criteria. Results: Available evidence indicates that HIV contributes to cancer development through both direct and indirect mechanisms: viral proteins such as Tat, Nef, and Vpr disrupt apoptosis, DNA repair, and cell cycle regulation, while chronic immune activation, persistent inflammation, and immunosuppression impair tumor immune surveillance and facilitate oncogenic viral co-infections, including Epstein–Barr virus, human papillomavirus, and human herpesvirus 8. Emerging pathways, such as epigenetic alterations, microRNA dysregulation, metabolic reprogramming, and the contribution of HIV reservoirs to pro-tumorigenic microenvironments, further modulate cancer risk. Conclusions: HIV may function as a cofactor that enhances the effects of oncogenic viruses by promoting viral persistence and immune dysregulation; while biologically plausible, direct evidence linking HIV to amplification of tumorigenesis in humans remains limited. Full article

Background: People living with HIV (PLWH) constitute a vulnerable population during the COVID-19 pandemic; however, it remains uncertain whether long-term suppressive antiretroviral therapy (ART) restores sufficient immune competence to support robust hybrid immunity. While vaccination followed by breakthrough infection—termed hybrid immunity—typically elicits potent humoral responses in immunocompetent individuals, the functional quality and breadth of these responses against evolving Omicron subvariants remain poorly characterized in PLWH. This study aimed to assess functional antibody responses, including neutralizing activity and Fc effector functions, in vaccinated and unvaccinated PLWH who experienced breakthrough infection with Omicron subvariants BA.4/5 or BF.7. Methods: We enrolled three cohorts between December 5 and December 20, 2022: 25 HIV-negative individuals with breakthrough infection (BTI-HC), 20 ART-experienced PLWH with breakthrough infection following three-dose COVID-19 vaccination (BTI-HIV), and 10 ART-experienced PLWH with primary infection without prior vaccination (PI-HIV). All HIV-positive participants were receiving suppressive ART with regimens based on non-nucleoside reverse transcriptase inhibitors or integrase strand transfer inhibitors for a median of 3.4 years. We measured receptor-binding domain (RBD)-specific IgG, neutralizing antibody titers against ancestral D614G, Delta, BA.1, BA.4/5, BF.7, XDV, KP.2, and KP.3 variants, and antibody-dependent cellular cytotoxicity (ADCC) responses. Results: Despite lower absolute CD4⁺ T cell counts, BTI-HIV participants mounted RBD-binding IgG, neutralizing antibody, and ADCC responses that were comparable to BTI-HC and significantly exceeded PI-HIV across all tested variants. Both breakthrough infection cohorts exhibited immunological imprinting, with higher neutralizing titers against ancestral D614G than infecting BA.4/5 or BF.7 variants. Emerging variants XDV, KP.2, and KP.3 demonstrated substantial neutralization escape in all groups. PI-HIV showed markedly diminished neutralization breadth and failed to generate enough responses against all tested Omicron strains. Conclusions: Suppressive ART enables PLWH to mount hybrid immunity—conferred by vaccination followed by BF.7 or BA.4/5 breakthrough infection—with neutralizing and ADCC responses comparable to HIV-negative individuals, and significantly exceeding those of unvaccinated PLWH with primary infection. This underscores the critical role of vaccination in establishing effective hybrid immunity in this population. However, we observed immunological imprinting, with higher titers against ancestral strains than against infecting variants, and substantial escape by emerging sublineages XDV, KP.2, and KP.3 across all groups. These findings support prioritizing updated variant-containing vaccines for HIV-positive populations and reinforce the essential role of vaccination in this vulnerable group. Full article

Background: Annual influenza vaccination is a WHO-recommended strategy for preventing seasonal influenza and its associated severe complications in older adults. Nevertheless, influenza vaccine effectiveness is often reduced in the elderly population and there remains an ongoing debate regarding whether repeated vaccination attenuates immune response. Methods: We conducted a prospective observational study to estimate the trivalent inactivated influenza vaccine-induced antibodies in older adults vaccinated for two consecutive years (2022–2023 and 2023–2024) and those with vaccines administered in a single season (2023–2024). Serum samples were collected concurrently with vaccination and at 30 and 90/180 days post-vaccination for hemagglutination inhibition (HAI) tests. Results: The participants administered two consecutive vaccinations had markedly higher pre-vaccination geometric mean titers (GMTs) and seroprotection rates for influenza A/H1N1 and A/H3N2. However, no intergroup differences were observed for H1N1, H3N2 or B/Victoria strains at 30, 90, or 180 days post-vaccination. At 30 days post-vaccination, participants with two consecutive influenza vaccinations showed significantly lower fold rises against the three strains and seroconversion rates (SCRs) for H1N1 and H3N2. The results of the subgroup analyses were largely consistent with the primary findings, with the exception of the A/H1N1 strain among individuals with pre-vaccination titers <1:10 at day 30. Conclusions: Immune responses vary by antigen type, and the influenza vaccine induces comparable serological response in the elderly, irrespective of their prior vaccination history. Full article

In recent years, fractional HIV models have received increasing attention. This study derives a fractional HIV model using the continuous-time random walk (CTRW) method, endowing the mathematical model with physical significance. Based on the transmission characteristics of HIV, the proposed model considers extrinsic infectivity, intrinsic infectivity, and drug control, specifically as follows: the extrinsic infectivity is a constant independent of the infection time; the intrinsic infectivity is a power-law function that depends on drug efficacy and infection time; the drug efficacy rate follows a Mittag–Leffler distribution with a long-term effect. Based on these considerations, a fractional HIV model with drug control is established in this paper. In addition, the global asymptotic stability of the equilibrium and the sensitivity analysis of the basic reproduction number $R_0$ are studied, and the theoretical results are verified by numerical simulations. The results show that reducing extrinsic infectivity, controlling intrinsic infectivity, and the drug efficacy rate are crucial in controlling the spread of HIV. Full article

Microglia, the resident macrophages of the central nervous system (CNS), serve as the primary reservoir of HIV-1 in the brain and play a crucial role in the development of HIV-1-associated neurocognitive disorders (HAND). While long non-coding RNAs (lncRNAs) have emerged as essential regulators of HIV-1 replication in T cells and macrophages, their role in microglia remains poorly understood. Here, we performed RNA sequencing of polyadenylated transcripts from a human microglial cell line exposed to HIV-1 infection or TNF-α stimulation to investigate transcriptional responses and identify lncRNAs with potential regulatory functions. Gene set enrichment analysis revealed broad overlap between viral and inflammatory responses, reflecting convergence on common molecular pathways. Among differentially expressed lncRNAs, we focused on TALAM1, which was specifically induced by HIV-1, and LINC00702, which responded to both HIV-1 and TNF-α. Validation by RT-qPCR confirmed the upregulation of TALAM1 and LINC00702 at 24 h post-infection. Furthermore, knockdown of either lncRNA affected viral genomic RNA levels, while only LINC00702 knockdown affected p55 production. Given that subcellular localization informs lncRNA function, we assessed the distribution of TALAM1 and LINC00702. TALAM1 was predominantly cytoplasmic under basal conditions but shifted toward nuclear enrichment upon HIV-1 infection, whereas LINC00702 remained primarily nuclear regardless of infection status. Consistent with their genomic context, protein interaction predictions, and pathway enrichment analyses suggested that TALAM1 may influence RNA processing and splicing, whereas LINC00702 may contribute to translational regulation and is associated with proteins involved in immune responses. Together, these findings provide an initial characterization of lncRNA responses to HIV-1 infection in a human microglial cell line and identify TALAM1 and LINC00702 as candidates for future functional studies in the context of viral infection and neuroinflammation. Full article

Cytomegalovirus (CMV) pneumonia presents diagnostic challenges in AIDS patients, as plasma monitoring often fails to reflect pulmonary viral burden. This retrospective study evaluated the prognostic value of bronchoalveolar lavage fluid (BALF) CMV DNA loads in 189 AIDS patients with pulmonary infections and CD4⁺ T cell counts < 200 cells/μL. CMV DNA in BALF and plasma was quantified to analyze associations with immune status and 90-day all-cause mortality. CMV detection was significantly more frequent in BALF (49.7%) than plasma (26.6%), indicating viral compartmentalization. An optimal BALF cutoff of 10,000 copies/mL was established for mortality prediction. Patients exceeding this threshold exhibited significantly lower CD4⁺ counts, increased mechanical ventilation requirements (34.4% vs. 11.5%), and prolonged hospital stays. Crucially, a BALF CMV load > 10,000 copies/mL was identified as an independent predictor of 90-day mortality (adjusted odds ratio = 3.78; 95% CI: 1.12–12.71). In conclusion, pulmonary CMV replication is prevalent and often compartmentalized in AIDS patients. A BALF CMV DNA load exceeding 10,000 copies/mL serves as a biomarker of profound immunosuppression and independently predicts poor clinical outcomes, highlighting the necessity of quantitative BALF monitoring for risk stratification. Full article