Search Results (3,973)

Cardiovascular disease (CVD) is increasingly recognized as a significant comorbidity in people living with HIV (PWH), contributing to increased morbidity and mortality. Epidemiological studies indicate that PWH have a 1.2–2-fold higher risk of myocardial infarction (MI) and other CVD events compared to HIV-negative individuals. While the mechanisms underlying HIV-associated CVD are not fully understood, they are likely to include a combination of cardiovascular-related adverse effects of HIV medications, vascular dysfunction caused by HIV-induced monocyte activation, and cytokine secretion, in addition to existing comorbidities and lifestyle choices. This comprehensive review examines the complex relationship between HIV infection and CVD, highlighting key pathophysiological mechanisms such as chronic immune activation, inflammation, endothelial dysfunction, and the role of antiretroviral therapy (ART) in promoting cardiovascular risk. Alongside conventional risk factors such as smoking, hypertension, and dyslipidemia, HIV-specific elements, especially metabolic abnormalities associated with ART, significantly contribute to the development of CVD. Prevention strategies are crucial, focusing on the early identification and management of cardiovascular risk factors as well as optimizing ART regimens to minimize adverse metabolic effects. Clinical guidelines now recommend routine cardiovascular risk assessment in PWH, emphasizing aggressive management tailored to their unique health profiles. However, challenges exist in fully understanding the cardiovascular outcomes in this population. Future research directions include exploring the role of inflammation-modulating therapies and refining sustainable prevention strategies to mitigate the growing burden of CVD in PWH. Full article

Epstein–Barr virus (EBV) is a key oncogenic pathogen implicated in the development of lymphomas, particularly among HIV-positive and immunocompromised individuals. While the association between EBV and lymphoma is well established, the mechanisms underlying progression from infection to malignancy—especially in the head and neck region—remain incompletely understood. This review offers a comprehensive analysis of the pathophysiological pathways by which EBV and HIV contribute to lymphomagenesis, with an emphasis on latency patterns, immune evasion, and epigenetic “hit and run” oncogenesis. Notably, it integrates novel findings on the diagnostic implications of EBV latency proteins, explores HIV-mediated B-cell dysregulation, and evaluates the emerging landscape of targeted therapies, including monoclonal antibodies and lytic cycle inducers. By focusing specifically on head and neck lymphomas, this review underscores a clinically underrepresented domain and offers insights that may guide future diagnostics, surveillance, and treatment strategies in vulnerable patient populations. This review also highlights the pressing need for improved animal models and continued research into EBV-specific therapeutic targets. Full article

Non-AIDS-defining cancers (NADCs) have emerged as an increasingly prominent cause of non-AIDS-related morbidity and mortality among people living with HIV (PLWH). However, the scarcity of NADC clinical samples, compounded by privacy and security constraints, continues to present formidable obstacles to advancing pathological and clinical investigations. In this study, we adopted a joint analysis strategy and deeply integrated and analyzed transcriptomic data from 12,486 PLWH and cancer patients to systematically identify potential key regulators for 23 NADCs. This effort culminated in NADCdb—a database specifically engineered for NADC pathological exploration, structured around three mechanistic frameworks rooted in the interplay of immunosuppression, chronic inflammation, carcinogenic viral infections, and HIV-derived oncogenic pathways. The “rNADC” module performed risk assessment by prioritizing genes with aberrant expression trajectories, deploying bidirectional stepwise regression coupled with logistic modeling to stratify the risks for 21 NADCs. The “dNADC” module, synergized patients’ dysregulated genes with their regulatory networks, using Random Forest (RF) and Conditional Inference Trees (CITs) to identify pathogenic drivers of NADCs, with an accuracy exceeding 75% (in the external validation cohort, the prediction accuracy of the HIV-associated clear cell renal cell carcinoma model exceeded 90%). Meanwhile, “iPredict” identified 1905 key immune biomarkers for 16 NADCs based on the distinct immune statuses of patients. Importantly, we conducted multi-dimensional profiling of these key determinants, including in-depth functional annotations, phenotype correlations, protein–protein interaction (PPI) networks, TF-miRNA-target regulatory networks, and drug prediction, to deeply dissect their mechanistic roles in NADC pathogenesis. In summary, NADCdb serves as a novel, centralized resource that integrates data and provides analytical frameworks, offering fresh perspectives and a valuable platform for the scientific exploration of NADCs. Full article

People living with HIV-1 (PLWH) are part of the so-called “fragile” populations to which COVID-19 vaccines were/are strongly recommended. The fact that most widely used COVID-19 vaccines rely on the production of a biologically active SARS-CoV-2 Spike protein expressed by synthetic mRNA poses the relevant question of whether and how this vaccination influences the fate of the HIV-1 reservoir. This report presents a detailed analysis of the literature data on the effects of SARS-CoV-2 Spike and COVID-19 vaccines on HIV-1 latently infected cells. Despite being limited in number, the experimental evidences consistently indicate that vaccine mRNA and/or SARS-CoV-2 Spike can effectively reactivate latent HIV-1. This conclusion has been drawn after “in vitro”, “ex vivo”, and “in vivo” assays, and with virus-associated Spike, soluble Spike, or its intracellular expression, as well as with COVID-19 mRNA vaccines. On the other hand, real-world observations on vaccinated PLWH under antiretroviral therapy (ART) provided evidence of HIV-1 reactivation almost exclusively in PLWH with unsuppressed viremia, as measured in terms of size of the HIV-1 reservoir. Although several issues still need to be clarified through urgent additional investigations, these data suggest the possibility that the Spike protein and/or the vaccine mRNA molecules affect the HIV-1 latency in PLWH. Full article

This study aims to explore characteristics and clinical predictors of Lymphogranuloma venereum (LGV) and non-LGV Chlamydia trachomatis (Ct) serovars. We conducted a retrospective study on men who have sex with men (MSM) diagnosed with rectal or urethral Ct between 2015 and 2022 at the Infectious Diseases Unit of San Raffaele Scientific Institute, Milan, Italy. Nucleic acid amplification test with sequencing was used for Ct serovar determination. Individuals’ characteristics were described by median (interquartile, IQR) or frequency (%) and compared using Kruskal–Wallis or Chi-Square tests, as appropriate. Logistic regression model was used to identify predictors of LGV; multinomial logistic regression model, with LGV group as reference category, investigated factors associated with the LGV group (serovars L1, L2B, L2C), specific highly prevalent non-LGV serovars (D, E, G) or the non-amplifiable group. Overall, 211 MSM were included: 29.8% with LGV, 50.2% non-LGV and 19.9% non-amplifiable. Symptomatic cases were 46% of which 48% LGV; rectal infection was the most common (86%), followed by urethral (10%) and both sites (4%). People living with HIV were 91.5%; 31.3% had ≥1 concomitant STI and 65.4% ≥1 previous one. According to logistic regression analysis, after adjustment for the diagnosis of ≥1 concomitant and previous STI, LGV serovars were significantly associated with symptomatic infections (adjusted odds ratio, aOR = 6.05; 95%CI = 2.92, 13.13; p < 0.001) and anorectal site (aOR = 17.12; 95%CI = 3.17–319.17, p = 0.007) compared to non-LGV. Among MSM, almost 30% of Ct infections were due to LGV serovars. Presence of symptoms and anorectal site involvement, identified as clinical predictors of LGV, should guide clinicians during diagnosis. Full article

Lamivudine/dolutegravir (3TC/DTG) is an effective and well-tolerated antiretroviral regimen for most people with HIV (PWH) who are virologically suppressed; however, specific clinical characteristics, such as prior hepatitis B virus (HBV) exposure or archived resistance-associated mutations (RAMs), may influence the risk of virological failure (VF). We conducted a retrospective, monocentric cohort study to evaluate the incidence and predictors of VF among PWH who switched to 3TC/DTG after achieving virological suppression (HIV-RNA < 50 copies/mL). A total of 188 PWH were included. Over 5082 patient-years of follow-up (PYFU), 8 individuals (4.3%) experienced VF, corresponding to an incidence rate of 1.45 per 1000 PYFU. The cumulative probabilities of VF at 1, 2, 3, 4, and 5 years were 0.6%, 2.7%, 2.7%, 4.2%, and 22.3%, respectively. In exploratory multivariable analyses, anti-HBc positivity was associated with an increased risk of VF (adjusted hazard ratio [aHR] 4.80, 95% CI 1.03–22.43; p = 0.046). After adjustment for age and sex, individuals with anti-HBc positivity who had switched from a tenofovir-containing regimen showed the highest risk of VF compared with anti-HBc-negative individuals without prior tenofovir exposure (aHR 15.06, 95% CI 1.40–161.38; p = 0.025). Given the limited number of virological events, these findings should be interpreted with caution. Nevertheless, they suggest that prior HBV exposure, particularly in the context of tenofovir discontinuation, may represent a clinically relevant factor when considering simplification to 3TC/DTG. Full article

HTLV-1 and HIV-1 represent biologically significant, structurally close, and equally problematic yet divergent human retroviruses. Although both infect CD4+ T cells and share similar structural elements, they differ markedly in genomic stability, transmission dynamics, clinical progression, and, most importantly, their transcriptional regulatory mechanisms. HTLV-1, an ancient virus with a limited global burden, often remains asymptomatic for decades before potentially causing ATL or HAM/TSP. Conversely, HIV-1, a relatively recent zoonotic transmission, undergoes rapid replication, exhibits high genetic diversity, and causes progressive immunodeficiency unless controlled by antiretroviral therapy (ART). At the molecular level, HTLV-1 maintains proviral latency through a balanced bidirectional transcription of regulatory genes (e.g., Tax and HBZ) that manipulate host transcription and immune evasion pathways, facilitating persistence and oncogenesis. HBZ and Tax were shown to contribute to driving the progressive acquisition of Treg-like and HLA class II phenotype in chronically activated CD4+ T-cells, promoting tolerogenic antigen presentation and immune evasion in ATL cells. This well-controlled differential expression of HTLV-1 regulatory genes is attributed to multiple intragenic virus regulatory mechanisms, which will be discussed in this review. In contrast, HIV-1 transcription is driven by a tightly regulated 5′ LTR promoter involving host factors such as NF-κB, Sp1, AP-1, and NFAT, among others, with strong influence imposed by the landscape of the provirus integration site, playing a pivotal role in latency and reactivation. The distinct regulatory circuitry of each virus suggests a key difference in their essential regulation, with HTLV-1 primarily relying on intragenic mechanisms, while HIV-1 relies more heavily on interactions with the surrounding host environment to control its expression. This difference underscores unique therapeutic challenges in managing viral latency, persistence, and pathogenesis. Full article

Defective HIV-1 proviruses harboring mutations and/or large internal deletions represent the majority of HIV-1 sequences found in circulating peripheral blood mononuclear cells of people living with HIV with viremia suppressed by combination antiretroviral therapy; indirect evidence suggests that such sequences are transcriptionally active and may contribute to immune activation. In this study, we present a new approach allowing for high-efficiency screening, immortalization, and targeted enrichment of HIV-positive CD4⁺ T-cells isolated from people living with HIV. Using this method, we were able to isolate and expand patient-derived cells, identify mutations and deletions via sequencing, and confirm that those proviruses were transcriptionally and translationally active in vitro. Moreover, our findings indicate that the majority of proviral sequences circulating in suppressed HIV-infected patients may undergo 3′-LTR deletions, suggesting that sequence diversity reported using LTR-to-LTR amplification and sequencing approaches may indeed be underscored. Full article

Background: Sexually transmitted infections (STIs) represent a significant public health problem due to their impact. Knowledge about them, perceptions of the risk of contracting them, and adherence to prevention strategies such as HPV vaccination are, at various levels, key factors in preventing the spread of STIs. The study therefore aimed to investigate and evaluate, in a group of young Italians, the level of knowledge, perception of risk and propensity to adhere to preventive strategies, including vaccination against papillomavirus. Methods: A cross-sectional study was conducted by administering a questionnaire to young people aged between 16 and 30, residing in four macro-geographical areas, collecting socio-demographic, behavioral and knowledge data. Levels of knowledge about STIs and HPV were classified into four categories (low, medium without awareness, medium with awareness, high). Risk perception was assessed on a scale of 1 to 10. Results: A total of 2576 questionnaires were collected, revealing that general knowledge about STIs is limited: only 12.5% of participants demonstrated a high level of knowledge, while 27.1% demonstrated a low level; with regard to HPV, 41.3% of the sample demonstrated a low level of knowledge. The perception of the risk of contracting HIV and HPV was low in most subjects (average score of approximately 2.9 out of 10), with no significant differences related to levels of knowledge about HPV. Potential adherence to HPV vaccination was high (83.0% considered vaccination useful), but among unvaccinated subjects, almost half expressed concerns about vaccination, related to poor knowledge and mistrust of vaccines in general. Factors associated with a higher frequency of self-reported STIs included older age, transgender identity, non-heterosexual orientation, and risky sexual behavior. Conclusions: The results emerging from the study highlight the urgent need to strengthen educational and preventive interventions aimed at young people. Raising awareness of the risk of contracting STIs and the importance of vaccination are key targets for health promotion interventions. Full article

Background: Survivin is an anti-apoptotic protein highly expressed during embryonic development and, in adults, mainly in the gastrointestinal epithelium. Its levels decrease in human gastric tissue and cultured cells upon exposure to Helicobacter pylori gamma-glutamyl transpeptidase (GGT), though the underlying mechanism remains unclear. Objective: We aimed to investigate the role of cap-independent translation driven by the Survivin 5′ untranslated region (5′UTR) in response to H. pylori infection in vitro. Methodology: Human cell lines (AGS, GES-1, HeLa, HEK293T) were used alongside bicistronic and monocistronic (Firefly/Renilla luciferases) reporter assays to assess short and long variants of the Survivin 5′UTR and HIV-1 internal ribosome entry site (IRES) sequences. Additional methods included in vitro transcription/translation, RT-qPCR, agarose gel electrophoresis, Western blotting, coupled/uncoupled translation assays, and siRNA silencing. Results: The short variant of the Survivin 5′ UTR supported cap-independent translation, like the HIV-1 IRES. Notably, H. pylori infection suppressed this translation in a GGT-dependent manner in gastric cells, and a similar reduction was observed following treatment with ATO, a known prooxidant. Conclusion: The Survivin 5′UTR exhibits cap-independent translation activity that is inhibited by H. pylori in a GGT-dependent manner, likely via oxidative stress. This mechanism helps to explain the downregulation of Survivin during gastric infection and indicates that oxidative stress can negatively affect both cellular and viral IRES-mediated translation. Full article

Prior to the introduction of antiretroviral therapy (ART), people with HIV (PWH) had high risk of fungemia. No systematic review has assessed the prevalence of fungemia in PWH after the introduction of combination ART in 1996. The primary objective of this systematic review was to determine the prevalence of fungemia in adult PWH after 1996. Furthermore, we aimed to compare the prevalence of fungemia in different ART time periods to determine geographic differences and fungal pathogen distribution. A systematic literature search was performed on 7 March 2025 across six databases and the study quality was assessed using the Newcastle–Ottawa scale. Prevalence estimates were extracted, and a meta-analysis was performed using a random effects model. Twelve studies comprising 27,729 PWH were included. The overall pooled prevalence in PWH was 3.3% (95% CI: 1.53; 4.96%, I² = 98.9%). The most common pathogen to cause fungemia was Talaromyces marneffei with a prevalence of 4.8%, although this pathogen was limited to studies from Asia. The highest prevalence of fungemia in PWH was 6.8% in Asia. The prevalence of fungemia was 5.8% between July 1996–September 2015 and 1.0% between September 2015–January 2025, but the difference was not statistically significant (p = 0.273). However, all findings were limited by very low certainty of evidence and should be interpreted with caution. In conclusion, our findings suggest that fungemia persists among PWH despite ART, especially in Asia. Given the limited available evidence, it was not possible to determine whether the prevalence of fungemia changed following the change in ART treatment guidelines in September 2015. The protocol is registered in PROSPERO (CRD420251005081). Full article

Although neurological disease is common in people with human immunodeficiency virus (HIV) (PWH), the contributing factors and underlying inflammatory mechanisms remain challenging to identify. Extracellular vesicles (EVs) constitute a relatively uncharacterized modality of intercellular communication and bioactive cargo transport in the setting of viral infection and pathogenesis. EVs carry inflammatory mediators to areas of the periphery during antiretroviral therapy (ART) suppression but are understudied in the brain. Using a biologically relevant simian–human immunodeficiency chimeric virus with a clade D HIV envelope (SHIV.D)-infected rhesus macaque (RM) model of HIV persistence in the central nervous system (CNS), we investigate circulating EV populations and the protein cargo of myeloid-derived EVs during SHIV infection. Using EV flow cytometry to quantify specific EV subpopulations, we found a significant increase in TMEM119+ microglial EVs and CD171+ neuronal EVs in RM plasma during viremia and ART suppression. Using primary RM monocyte-derived macrophages (MDMs), we determined that MDMs increased EV production after SHIV infection. Whole proteomic analysis of these EVs demonstrated that myeloid EVs isolated from SHIV.D-infected MDMs carried significantly increased levels of neuropathogenic and inflammatory proteins. Altogether, these studies improve our understanding of the contribution of myeloid EVs to neurological disease during SHIV/HIV infection. Full article

Background: Men who have sex with men (MSM) using HIV pre-exposure prophylaxis (PrEP) experience a high burden of human papillomavirus (HPV) infection and related diseases, yet data on HPV vaccination among this group in Brazil remain limited. Aims: The aims of this study were to estimate the prevalence of complete HPV vaccination and to identify factors associated with vaccination completion among MSM using PrEP in Brazil. Methods: We conducted a cross-sectional online survey between May and September 2025 among MSM aged ≥18 years, residing in Brazil and currently using oral PrEP. Participants were recruited through virtual snowball sampling and targeted advertisements on social media and a gay geosocial networking application. Data were collected using a structured, self-administered questionnaire hosted on REDCap^®. Complete HPV vaccination was defined as self-reported receipt of all doses recommended according to the participant’s age and clinical condition. Sociodemographic characteristics, relationship patterns, sexual behaviors, lubricant use during sexual activity, and history of sexually transmitted infections (STIs) were assessed. Adjusted prevalence ratios (aPRs) and 95% confidence intervals (95% CIs) were estimated using Poisson regression with robust (sandwich) variance. Results: A total of 872 MSM using PrEP were included, of whom 59.4% reported complete HPV vaccination. In adjusted analyses, complete vaccination was more frequent among participants reporting both steady and casual partners (aPR = 1.90; 95% CI: 1.36–2.65) or only casual partners (aPR = 1.72; 95% CI: 1.24–2.39), those reporting lubricant use during sexual activity (aPR = 1.41; 95% CI: 1.23–1.61), and those with a diagnosis of chlamydia and/or gonorrhea in the previous 12 months (aPR = 1.22; 95% CI: 1.08–1.36). Conclusions: Although HPV vaccination coverage among MSM using PrEP in Brazil is higher than that reported for MSM in general, it remains incomplete in a population with regular contact with specialized health services. Integrating systematic assessment and delivery of HPV vaccination into PrEP care may help increase vaccination completion and reduce missed opportunities for prevention. Full article

The HIV epidemic in Romania started in the late eighties with a large cohort of children nosocomially infected with subtype F1 strains, in parallel with sexual transmission. The purpose of the present study was to investigate the transmitted drug resistance (TDR), subtype distribution, and transmission clusters among persons diagnosed with HIV between 2019 and 2022 in Romania. The prototype of a person recently diagnosed with HIV in Romania is male, 20–50 years old, a late presenter, infected with F1, B, or A subtype. The rate of TDR varied over time, from 5% in 2019 to 15% in 2022. TDR affected mainly the first generation of NNRTIs and the PI class. The rate of late presentation was almost 60%, with 35% of persons qualifying as very late presenters. Subtype F1 is still preponderant in Romania, whereas other subtypes (B, A) and recombinants account for a quarter of HIV-1 new cases. Several transmission networks were identified in the study population, two of them associated with TDR in subtypes F1 and A1. The largest cluster consisted of 26 sequences, originating from Western Romania and introduced around 2007. Molecular clock analysis indicated different origin time points for different clusters, with the most recent in subtypes A1 and B, and the oldest in subtype F1. In conclusion, the HIV-1 epidemic in Romania is currently driven by sexual transmission, with MSM contribution continuously rising in recent years; there are also increases in TDR and the circulation of HIV-1 strains other than F1 (subtype B, A, recombinants). Full article

Background and Objectives: People living with HIV (PLWH) have excess osteoporosis and fractures not fully captured by dual-energy X-ray absorptiometry (DXA). We evaluated whether trabecular bone score (TBS), calcaneal quantitative ultrasound (QUS) and bone turnover markers improve vertebral fracture risk assessment beyond areal bone mineral density (BMD) in PLWH. Methods: In this cross-sectional study, 87 antiretroviral-treated adults undergoing DXA had lumbar spine TBS and calcaneal QUS. Morphometric vertebral fractures were identified, correlates of degraded TBS were analyzed using multivariable regression, and sequential logistic models quantified the incremental contribution of TBS and CTX to discriminate for prevalent morphometric vertebral fractures. Results: Low BMD (osteopenia/osteoporosis) was present in 62% of participants, degraded TBS in 37% and morphometric vertebral fractures in 17%. Degraded versus normal TBS was associated with older age (49.1 vs. 39.7 years), longer HIV duration and lower nadir CD4+ count, as well as more frequent tenofovir disoproxil fumarate exposure (66% vs. 52%; all p ≤ 0.04). In multivariable analysis, age (per 10-year increase; adjusted odds ratio [aOR] 1.78; 95% CI 1.13–2.83) and nadir CD4+ < 200 cells/mm³ (aOR 2.29; 95% CI 1.06–4.97) independently predicted degraded TBS. In sequential cross-sectional models for prevalent morphometric vertebral fractures, the area under the curve increased from 0.71 (clinical variables) to 0.79 after adding lumbar spine T-score and to 0.85 after adding TBS; adding CTX yielded 0.87 without a statistically significant incremental gain. Conclusions: In PLWH, TBS captures bone quality deficits and improves vertebral fracture risk discrimination beyond BMD, supporting its integration alongside DXA in routine HIV care. Full article