Search Results (366)

Background/Objectives: Despite medical advances, stigma remains a major challenge for people living with HIV (PLWH). This study examined clinical, sociodemographic, and psychological predictors of HIV-related stigma, and explored whether affective temperament moderates the impact of depression on stigma. Methods: This cross-sectional observational study included 97 PLWH attending a tertiary infectious disease unit in Rome, Italy. Participants completed a battery of validated psychometric instruments assessing depressive symptoms, anxiety, manic symptoms, mixed affective states, general psychopathology, impulsivity, and affective temperament. HIV-related stigma was evaluated using the Berger HIV Stigma Scale, which measures personalized stigma, disclosure concerns, negative self-image, and concerns with public attitudes. Descriptive statistics were used to characterize the sample. Univariate linear regressions were conducted to explore associations between clinical, psychometric, and sociodemographic variables and each stigma subdimension, as well as the total stigma score. Variables significant at p < 0.05 were included in five multivariate linear regression models. Moderation analyses were subsequently performed to assess whether affective temperaments moderated the relationship between significant psychopathological predictors and stigma. Bonferroni correction was applied where appropriate. Results: Higher depressive symptom scores are significantly associated with greater internalized stigma (B = 0.902, p = 0.006) and total stigma (B = 2.603, p = 0.008). Furthermore, moderation analyses showed that anxious temperament significantly intensified the relationship between depressive symptoms and both negative self-image (interaction term B = 0.125, p = 0.001) and total stigma (B = 0.336, p = 0.002). Conclusions: Depressive symptoms and anxious temperament are associated with HIV-related stigma. Integrating psychological screening and targeted interventions for mood and temperament vulnerabilities may help reduce stigma burden in PLWH and improve psychosocial outcomes. Full article

Improved antiretroviral therapy (ART) has significantly increased the life expectancy of people living with HIV (PLWH). At the same time, other complications like metabolic syndrome (MetS) are coming up as new challenges to handle. This review aims to explore the emerging evidence of gut microbiome and virome alterations in human immunodeficiency virus-1 (HIV-1) infection and associated metabolic disorders, such as type-2 diabetes (T2DM) and cardiovascular disease (CVD), with a focus on their interplay, contribution to immune dysfunction, and potential as therapeutic targets. We conducted a comprehensive review of the current literature on gut bacteriome and virome changes in HIV-1-infected individuals and those with metabolic comorbidities emphasizing their complex interplay and potential as biomarkers or therapeutic targets. HIV-1 infection disrupts gut microbial homeostasis, promoting bacterial translocation, systemic inflammation, and metabolic dysregulation. Similarly, metabolic disorders are marked by reduced beneficial short-chain fatty acid-producing bacteria and an increase in pro-inflammatory taxa. Alterations in the gut virome, particularly involving bacteriophages, may exacerbate bacterial dysbiosis and immune dysfunction. Conversely, some viral populations have been associated with immune restoration post-ART. These findings point toward a dynamic and bidirectional relationship between the gut virome, bacteriome, and host immunity. Targeted interventions such as microbiome modulation and fecal virome transplantation (FVT) offer promising avenues for restoring gut homeostasis and improving long-term outcomes in PLWH. Full article

Introduction: Human immunodeficiency virus (HIV)-associated neurocognitive impairment (NCI) remains a concern despite combination antiretroviral therapy (cART), with cognitive problems often persisting even after viral suppression. The mechanisms underlying neurocognitive deterioration in people living with HIV (PLWH) and the role of plasma biomarkers remain unclear. This study aims to evaluate neurocognitive trajectories and biomarker changes in a real-world cohort of newly diagnosed PLWH initiating cART in Greece. Methods: This prospective, single-center study assessed neuropsychological performance and plasma biomarkers in treatment-naïve PLWH at baseline and 18 months after cART initiation. HIV-associated neurocognitive disorder (HAND) was classified using the Frascati criteria, and plasma biomarkers of inflammation and monocyte activation were measured. Correlations between biomarkers and cognitive performance were analyzed. Results: A total of 39 treatment-naïve PLWH were enrolled in this study. At baseline, 45.7% of participants met criteria for HAND, predominantly, asymptomatic neurocognitive impairment (ANI). Over 18 months, neurocognitive function improved, particularly in speed of information processing, executive function, and visuospatial ability, while verbal fluency, fine motor dexterity, and attention/working memory remained unchanged. Biomarkers of inflammation and monocyte activation decreased following cART, except for neopterin, which increased (10.6 vs. 13 ng/mL, p = 0.002), and plasma NFL (7.5 vs. 7.2 pg/mL, p = 0.54), which remained stable. A negative correlation between monocyte activation markers and cognitive performance was observed only at follow-up, suggesting that systemic inflammation may mask these associations in untreated PLWH. Conclusions: Early cART initiation supports neurocognitive recovery and reduces immune activation in PLWH. The observed correlation between cognitive performance and monocyte activation markers after viral suppression highlights the potential utility of plasma biomarkers in predicting cognitive impairment. Full article

HIV-associated lymphoma (HAL) is a heterogeneous and highly aggressive group of malignancies. Although antiretroviral therapy (ART) has significantly prolonged the survival of people living with HIV (PLWH), the risk of malignancy secondary to HIV infection remains higher than in HIV-negative individuals, with HAL being among the most frequent. The pathogenesis of HAL is complex, involving multifactorial interactions. In current clinical practice, HAL faces a double challenge: the lack of effective biological risk warning systems and the lack of precise prognostic stratification tools. In recent years, the construction of multidimensional biomarker systems has shown critical value in the comprehensive management of HAL. This review aims to systematically summarize recent advances in circulating biomarkers for HAL, focusing on the potential applications of immune environment indicators, such as inflammatory cytokine profiles and microbial translocation markers, as well as serum protein profiles, lymphocyte subsets, extracellular vesicles (EVs), circulating microRNAs (miRNAs), and viral biomarkers. These biomarkers offer promising avenues for early risk prediction, therapeutic monitoring, and prognostic evaluation. Developing an assessment system based on multidimensional biomarkers will optimize early risk stratification, enable precise prognostic classification, and support personalized therapeutic strategies, thereby providing a novel theoretical basis and practical direction for the clinical management of HAL. Full article

The Undetectable = Untransmittable (U=U) message is a cornerstone of HIV-related public health communication, yet global levels of awareness and acceptance remain unclear across key populations. This study aimed to assess the global prevalence of awareness and acceptance of the U=U message among men who have sex with men (MSM), people living with HIV (PLWH), healthcare professionals, and the general population. A systematic review and meta-analysis was conducted using data from PubMed, Embase, and Google Scholar without language restrictions through 31 October 2023. Eligible studies included prospective cohort studies, randomized clinical trials, and cross-sectional studies reporting numerical data on U=U awareness and acceptance. From 1171 screened records, 43 studies were included. Data were analyzed using a random effects model. The findings showed that U=U awareness was high among PLWH, moderate among MSM and healthcare professionals, and low in the general population. Complete acceptance of U=U was low in MSM and the general population, and moderate in PLWH and healthcare professionals. Any acceptance was moderate among MSM and the general population, and high among PLWH and healthcare professionals. These results highlight the need for targeted education strategies to enhance understanding and reduce HIV-related stigma, particularly in populations with lower awareness and acceptance. Full article

The advent of effective antiretroviral therapy in the mid-1990s, which successfully prevented the progression to AIDS in people living with HIV (PLWH), was associated with the appearance of the so-called HIV-associated lipodystrophy. This condition involved subcutaneous fat atrophy; abdominal fat hypertrophy; and, in some cases, lipomatosis. It was also associated with systemic metabolic disturbances, primarily insulin resistance and dyslipidemia. Following the replacement of certain antiretroviral drugs, particularly the thymidine-analog reverse transcriptase inhibitors stavudine and zidovudine, with less toxic alternatives, the incidences of lipoatrophy and lipomatosis significantly declined. However, lipodystrophy resulting from first-generation antiretroviral therapy does not always resolve after switching to newer agents. Although the widespread use of modern antiretroviral drugs—especially integrase strand transfer inhibitors and non-lipoatrophic reverse transcriptase inhibitors such as tenofovir alafenamide—has reduced the incidences of severe forms of lipodystrophy, these regimens are not entirely free of adipose tissue-related effects. Notably, they are associated with weight gain that resembles common obesity and can have adverse cardiometabolic consequences. Recent evidence also suggests the hypertrophy of specific fat depots, such as epicardial and perivascular adipose tissue, in PLWH on last-generation treatments, potentially contributing to increased cardiovascular risk. This evolving landscape underscores the persistent vulnerability of PLWH to adipose tissue alterations. While these morphological changes may not be as pronounced as those seen in classic HIV-associated lipodystrophy, they can still pose significant health risks. The continued optimization of treatment regimens and the vigilant monitoring of adipose tissue alterations and metabolic status remain essential strategies to improve the health of PLWH. Full article

Background/Objectives: End-of-life (EOL) HIV cure research, which studies HIV persistence through pre- and post-mortem tissue collection, has focused primarily on people living with HIV (PLWH) with a prognosis of six months or less. However, the perspectives of long-term survivors (LTS) diagnosed before the advent of effective antiretroviral treatment (ART) remain underexplored. Understanding their motivations and concerns about EOL cure research is essential for creating inclusive and ethical research frameworks. Methods: Between 2023 and 2024, we conducted in-depth qualitative interviews with 16 PLWH aged 60 and older from diverse backgrounds across the United States, recruited through community-based organizations and HIV networks. We used inductive thematic analysis to explore LTS’ perspectives on EOL HIV research. Results: Participants included cisgender men (56.25%) and women (43.75%) with diverse racial identities. While participants supported EOL HIV cure research, their willingness to participate varied, influenced by awareness, logistics, and ethical concerns. Altruism-motivated participation, but misconceptions about procedures and concerns over bodily integrity represented potential barriers. Some viewed blood draws and leukaphereses as routine, while others expressed hesitancy with biopsies and post-mortem tissue retrieval. HIV stigma, historical mistrust, and cultural beliefs also played a role in willingness to participate. LTS emphasized the need for decentralized research sites, travel support, and financial safeguards. Conclusions: To include LTS in EOL HIV cure research, a community-driven approach is needed, focusing on clear communication, ethical considerations, logistical support, and linkages to EOL care. Addressing misconceptions and building trust, particularly within groups traditionally underrepresented in research, is essential to expanding participation. Full article

AIDS-related malignant lymphomas (ARLs) are the lymphomas that develop in association with HIV infection. According to the introduction of combination antiretroviral therapy (cART), the life expectancy of People Living with HIV (PLWH) has markedly improved; however, approximately one-third of PLWH have passed away from the complications of malignancies, even in well-controlled PLWH. HIV itself is not tumorigenic, and most of these tumors are due to co-infection with oncogenic viruses. γ-herpes viruses (Epstein–Barr virus: EBV and Kaposi sarcoma-associated herpesvirus: KSHV) are the most significant risk factors for ARLs. Immunodeficiency, chronic inflammation, accelerated aging, and genetic instability caused by HIV infection, as well as HIV accessory molecules, are thought to promote lymphomagenesis. The prognosis of ARLs is comparable to that of non-HIV cases in the cART era. Intensive chemotherapy with autologous stem cell transplantation is also available for relapsed/refractory ARLs. Since the early stage of HIV infection has no symptoms, significant numbers of HIV-infected individuals have not noticed HIV infection until the onset of AIDS (so-called Ikinari AIDS). Since the ratio of these patients is more than 30% in Japan, hematologists should carefully consider the possibility of HIV infection in cases of lymphoma. Even in an era of cART, ARL remains a critical complication in PLWH, warranting continuous surveillance. Full article

Background: The use of antiretroviral therapy (ART) has improved the lives of people living with HIV (PLWH). However, its use is associated with secondary complications, notably hepatotoxicity. This systematic review and meta-analysis assess the effects of HIV infection and ART on liver function in PLWH. Method: A comprehensive literature search was performed in PubMed, Scopus, and Google Scholar from inception to 12 February 2025. Studies analyzing liver enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in PLWH undergoing ART, those who are ART-naïve, and HIV-negative individuals were considered. Data analysis was performed using a meta-analysis web tool, and the results were reported as standardized mean differences (SMDs) and 95% confidence intervals (CIs). Results: Twenty-six studies were included in the meta-analysis. The findings showed an increase in AST, SMD = 1.85 (0.93 to 2.78, p < 0.0001, I² = 93.8%), and ALT, SMD = 2.65 (1.25 to 4.04, p = 0.0002, I² = 97.8%) in PLWH who were naïve compared with those who were HIV negative. Additionally, there was a pronounced elevation in AST, SMD = 1.49 (0.48 to 2.50, p = 0.0038, I² = 98%); ALT, SMD = 2.30 (1.14 to 3.45, p < 0.0001, I² = 98%); and ALP, SMD = 1.40 (0.55 to 2.26, p < 0.01, I² = 97%) in PLWH exposed to ART compared with HIV-negative individuals. However, there was no significant difference in ALP, SMD = 0.53 (–0.92 to 1.98, p = 0.4726, I² = 98%) between PLWH who were ART-naïve and HIV-negative individuals. Conclusions: The results show that HIV infection and ART administration are associated with elevated liver function test enzymes, suggesting that each may contribute to liver dysfunction among PLWH. These results highlight the dual risk posed by HIV infection and ART exposure. Full article

Human immunodeficiency virus (HIV) is responsible for acquired immunodeficiency syndrome (AIDS), a condition characterized by the depletion of CD4+ T lymphocytes, which predisposes individuals to opportunistic infections and, ultimately, death. Although antiretroviral therapy (ART) has substantially improved clinical outcomes, certain limitations persist. Notably, 15–30% of individuals undergoing ART achieve viral suppression but fail to restore adequate CD4+ T cell counts, being defined as immunological non-responders (INR) and remaining at increased risk of disease progression to AIDS. The impaired immune recovery in INRs is attributed to insufficient production and/or excessive destruction of CD4+ T lymphocytes, which can be modulated by autophagy process. This evolutionarily conserved mechanism is fundamental to lymphocyte development and activation as well as to programmed cell death pathways such as apoptosis, necroptosis, ferroptosis, and pyroptosis. These pathways are essential for understanding the impaired immune reconstitution observed in people living with HIV, whose inability to maintain immune homeostasis contributes to accelerated disease progression. This review explores the interplay between autophagy, HIV, and cell death mechanisms, highlighting its relevance in immunological recovery under ART and its potential as a therapeutic target. Full article

Although efficiently managed by cART, chronic HIV infection remains associated with a high incidence of malignant lymphomas. This diverse group of tumors presents considerable challenges in research, diagnosis, and treatment due to their complex pathogenesis, heterogeneous tumor microenvironment, and frequently aggressive clinical behavior. In this review, we examine the multifactorial pathogenesis of lymphomas arising in people living with HIV (PLWH), encompassing both direct and indirect oncogenic mechanisms. We summarize the key histopathological features and microenvironmental characteristics that may influence therapeutic responses. Current treatment strategies approved for the treatment of lymphomas in PLWH are showing outcomes comparable with those observed in patients without HIV. Notably, the immune reconstitution achieved through cART has renewed interest in immunotherapeutic approaches for HIV-associated lymphomas, with several strategies under clinical investigation. However, progress in the diagnosis and management of these malignancies is hindered by fragmented research efforts and the frequent exclusion of PLWH from pivotal clinical trials. Coordinated efforts are essential to overcome these barriers, reduce lymphoma incidence, and improve survival outcomes in this vulnerable population. Full article

Background/Objectives: This study aims to investigate the influence of demographic, behavioral, anthropometric, and comorbid factors on brain atrophy in people living with HIV (PLWH). Methods: We conducted a cross-sectional study involving 121 HIV-positive patients, stratified into two groups, those with and without brain atrophy (BA). For each participant, we recorded demographic data, smoking status, physical activity levels, disease and treatment duration, and comorbidities. BA was quantitatively assessed using MRI-derived volumetric measurements of 47 cerebral substructures. Results: Patients with BA exhibited significantly reduced gray matter (GM) and white matter (WM) volumes alongside increased cerebrospinal fluid volumes, both in absolute and percentage measurements. WM atrophy was most pronounced in the frontal, parietal, and temporal lobes, with relative sparing of the occipital lobe. GM atrophy predominantly affected the basal ganglia (notably, the thalamus and putamen) and cortical regions, including the hippocampus, frontal, and parietal lobes. Significant positive correlations were observed between BA and both smoking status (pack–years) and disease duration, while physical activity demonstrated an inverse relationship (higher atrophy risk in those with less than 30 min of daily continuous walking). Non-adherence to antiretroviral therapy (ART) was also associated with BA. Among comorbidities, type 2 diabetes and HIV-associated neurocognitive disorders (HAND) showed the strongest associations with BA. Conclusions: Brain atrophy in PWH is correlated with smoking, physical inactivity, and the duration of HIV infection. Comorbid conditions, such as type II diabetes and HAND, amplify the risk for BA. We consider that early lifestyle interventions and optimized ART may mitigate the neurodegeneration process. Full article

Background and Objectives: This study explores the immunogenetic associations of human leukocyte antigens (HLAs) and cytokine levels in people living with HIV/AIDS (PLWH) who exhibit HIV-related skin disorders. HIV-related skin disorders, including inflammatory eruptions, atopic and seborrheic dermatitis, psoriasis, and pruritic papular eruption, are common among PLWH. These conditions may be influenced by genetic and immunological factors. This study aims to investigate the associations between HLA class II alleles, cytokine levels, and the presence of HIV-related dermatoses, providing insights into genetic susceptibility and immune mechanisms. Materials and Methods: This study included 115 PLWH with HIV-related skin disorders and a control group of 80 healthy individuals. HLA allele frequencies were analyzed, and cytokine levels (IL-1β, IL-10, IFN-y) were measured in blood samples. Statistical analyses were performed to identify significant differences in allele frequencies and cytokine responses between the groups. Results: Risk alleles (DQB1*0201:0301, OR = 19.4 and DQA1*0101:0501, OR = 4.2) and protective alleles (DRB1*07:13, OR = 0.19, DRB1*01:13, OR = 0.09, DRB1*04:11, OR = 0.07, and DQA1*0501:0501, OR = 0.24) showed statistically significant differences in frequency (p < 0.05) between PLWH and healthy controls. The protective DQA1*0501:0501 allele was associated with elevated levels of IL-1β (p < 0.001, r = 0.79) and IL-10 (p = 0.010, r = 0.63). Increased IL-1β levels may enhance immune responses, while higher IL-10 levels may exert anti-inflammatory effects, potentially reducing susceptibility to HIV-related dermatoses. Regression analysis revealed that IL-1β (Exp(B) = 0.76, p < 0.001) and IFN-γ (Exp(B) = 1.06, p = 0.043) are significant predictors for the likelihood of developing HIV-related dermatoses. An increase in IL-1β levels reduced this likelihood by 24%, while an increase in IFN-γ levels increased it by 6%. Conclusions: The findings emphasize the interaction between HLA class II alleles and cytokine profiles in determining genetic risk and clinical outcomes in PLWH with HIV-related skin disorders. Protective alleles, such as DQA1*0501:0501, may contribute to immune regulation, offering potential targets for therapeutic interventions in PLWH with dermatoses. Our results highlight the importance of IL-1β and IFN-γ as key modulators in the progression of HIV infection and the development of HIV-related dermatoses. Further research is needed to explore the mechanisms underlying these associations, particularly in the Latvian population, to inform targeted therapeutic strategies. Full article

Inflammation is a crucial component of the immune response essential for host defense and tissue repair. However, when the immune response becomes dysregulated, it can contribute to the pathogenesis of chronic diseases. While acute inflammation is a short-lived, protective response, chronic inflammation is sustained over time and can lead to immune dysfunction, tissue damage, and disease progression. The chronic inflammation theory of disease suggests that persistent immune activation/inflammation underlies both infectious and non-infectious conditions and serves as a unifying mechanism across distinct pathological states. In this review article, we argue that human immunodeficiency virus (HIV) infection represents a prime model for studying chronic inflammation, and that despite effective viral suppression with antiretroviral therapy (ART), people living with HIV (PLWH) exhibit persistent immune activation, systemic inflammation, and an increased risk of cardiovascular, metabolic, and neurodegenerative diseases. Here, the interplay between microbial translocation, immune dysregulation, and metabolic reprogramming fuels a state of chronic inflammation that accelerates disease progression beyond HIV itself. Key factors such as T-cell exhaustion, persistent monocyte/macrophage activation, and immunometabolic dysfunction contribute to such a sustained inflammatory state. This review explores the molecular and cellular mechanisms driving chronic inflammation in HIV infection with a focus on immunometabolism and its implications for broader inflammatory diseases. By understanding such pathways, we can identify novel therapeutic targets to mitigate inflammation-driven disease progression not only in HIV but across a spectrum of chronic inflammatory conditions. Full article

The COVID-19 pandemic triggered a public health crisis that significantly impacted sexually transmitted infections (STIs), particularly syphilis. However, data on syphilis incidence during the pandemic remains inconsistent globally. Key groups affected include women of reproductive age, pregnant women, individuals living with HIV, and men who have sex with men (MSM). This paper reviews available literature from databases such as PubMed, Scopus, and Google Scholar to analyse the pandemic’s influence on congenital and gestational syphilis, focusing on high-risk populations. We discuss the pandemic’s impact on the incidence of gestational and congenital syphilis, including changes in screening and treatment protocols. Additionally, we examine alterations in syphilis prevalence and testing among people living with HIV and MSM, including implications observed in blood donors. The findings underscore the consequences of impaired STI diagnostics for public health. We emphasise the need for uninterrupted access to diagnostics and treatment during public health crises. To prevent rising syphilis rates post-pandemic, it is crucial to implement robust education and accessible testing measures. Full article