Search Results (27)

The objectives of our study were to determine the mortality rates, causes, and risk factors of people living with HIV in the modern antiretroviral therapy era, in a major HIV center in Israel. We retrospectively collected data from 1547 patients treated during 2001–2021. We used the Shapiro–Wilk test, Fisher’s exact test, Student’s t test, and chi-square to compare between patients who died and those who did not, and between patients who died from AIDS-related and non-AIDS-related causes. In total, 206 (13.3%) patients died. The causes of death were AIDS-defining diseases (33.5%), cardiovascular diseases (21.8%), non-AIDS infections (16%), and hepatic disorders (7%). The annual mortality rate was 1.31 ± 0.3%. Despite an increase in age (35 ± 13.2 in 2001, 49 ± 13.6 years in 2021; p < 0.001), the mortality rate decreased (2.12% during 2005–2008, 0.71% during 2018–2021; p = 0.0001). AIDS-defining diseases caused 75% of deaths during 2001–2002, and only 25% during 2019–2021. The proportion of cardiovascular deaths increased (8.3% in 2001–2003, 33.3% in 2019–2021; p < 0.001). Low CD4 and high viral load at diagnosis, male gender, non-MSM HIV acquisition (heterosexual transmission and people who inject drugs), and inability to achieve viral suppression because of non-compliance were risk factors for mortality. Mortality rates decreased during 2001–2021; however, the proportion of non-AIDS deaths increased. Early cardiovascular comorbidity screening and targeted adherence interventions in non-MSM populations and in patients with low CD4 are needed. Full article

Background: After the implementations of Highly Active Antiretroviral Therapy (HAART) HIV infection became a chronic condition and the clinical focus on non-AIDS-related comorbidities such as hypertension and chronic kidney disease has increased. This study aims to investigate the prevalence and independent predictors of hypertension and albuminuria in a cohort of people with HIV (PWHIV) with high rates of viral suppression. Methods: This is a cross-sectional study of 183 HAART-experienced PWHIV. Hypertension, defined as office systolic blood pressure of ≥140 mmHg or diastolic blood pressure of ≥90 mmHg and albuminuria, was defined as a sex-based albumin–creatinine ratio (ACR) of >355 mg/g for females and >250 mg/g for males. Univariable and multivariable logistic regression was conducted to identify the association of hypertension and albuminuria with demographic, clinical, and HIV-specific factors. Results: The prevalence of hypertension was 43.9% (n = 74) and albuminuria was 22.4% (n = 41). In the multivariable analysis, factors independently associated with prevalence of HTN were older age, overweight/obesity, and diabetes mellitus. TDF-based ART was explored as a potential factor but did not reach statistical significance (aRR = 1.85, p = 0.065). For albuminuria, older age, diabetes mellitus, and duration of HAART (aRR = 1.03 per year) were revealed as independent predictors. Conclusions: The results of this study demonstrate that the development of hypertension is primarily driven by traditional metabolic risk factors. However, the progression to albuminuria appears to be influenced not only by these comorbidities but also by long-term HIV disease and HAART exposure. These findings underline the critical need for the screening and management of hypertension and other comorbidities to mitigate the risk of long-term cardiovascular and renal complications in this aging population of PWHIV. Full article

The use of highly active combined antiretroviral therapy (cART) has increased life expectancy in people living with HIV (PLWH). As a result of ongoing monitoring and surveillance in established HIV out-patient clinics, thyroid dysfunction amongst this population has become increasingly reported. In this narrative review, primary studies, case reports, and meta-analyses published on PubMed, Embase, and Cochrane were analysed. The most reported thyroid dysfunction is subclinical hypothyroidism (SCH). The prevalence of subclinical hypothyroidism was as high as 40% in PLWH with CD4 T-cell count < 350 cells/mm³, which is a level indicating a state of immunosuppression. Some less commonly reported thyroid dysfunctional conditions include overt hyperthyroidism and thyroid malignancy. Reports have linked the development of thyroid dysfunction to the use of cART, leading to immune reconstitution inflammatory syndrome (IRIS), which has also been linked to the development of Grave’s disease (GD). It is also important to check for thyroid malignancy, as PLWH are prone to having a high risk of developing non-AIDS-related or -defining cancer (NADC). Most research suggests symptom-driven monitoring. However, evidence also suggests that monitoring with cART status change, monitoring for patients with significant comorbidities, or with immune reconstitution may be useful. The screening should include Free Thyroxine (FT4), triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) testing. Furthermore, vigilance for Grave’s disease and performing thyroid antibody checks are advised, especially once the reconstitution of T-cells is achieved. Full article

People living with the human immunodeficiency virus (PLWH) are continually subjected to challenges involving the development of non-acquired immunodeficiency syndrome (AIDS)-related comorbidities despite the effectiveness of highly active antiretroviral therapy (HAART). Exacerbated oxidative stress, which is intrinsically linked to chronic inflammation, is implicated in non-AIDS comorbidities, including the increased risk of cardiovascular disease (CVD) observed in PLWH. Here, we review evidence on the potential pathological implications of myeloperoxidase (MPO), a leukocyte-derived enzyme and a key mediator of oxidative stress and inflammation, in driving CVD-related complications in PLWH. A systematic review approach was taken to identify relevant clinical studies through searches of Cochrane Libraries, PubMed, Web of Science, ScienceDirect, and Google Scholar, up to the 30 June 2025. The summarized data appraised clinical studies (n = 14) on adults (n = 1445) with a mean age of 45 years reporting on the association between MPO and enhanced lipid peroxidation marked by elevated concentrations of oxidized low-density lipoprotein cholesterol (oxLDL-C) in PLWH. Such results were consistent with elevated inflammatory markers, including high sensitivity C-reactive protein (hsCRP), which was also linked with endothelial dysfunction. There is a lack of evidence linking the duration of HAART to MPO levels or an increased risk of CVD. However, there is room to explore whether enhanced levels of oxLDL-C, in association with sustained MPO activation, could drive CVD risk in PLWH. The present review provides essential information on the pathological relevance of MPO in endothelial dysfunction and CVD risk in PLWH. Full article

Systemic sclerosis (SSc) is an autoimmune disease associated with a high burden of morbidity and mortality due to organ complications. Pulmonary arterial hypertension (PAH) and cardiac involvement, characterized by chronic right ventricular (RV) pressure overload with consequent RV dysfunction and ultimately right heart failure (HF), are among these. A common comorbidity in SSc is chronic kidney disease (CKD). CKD is often present at the time of PAH diagnosis or a decline in renal function may occur during the course of the disease. CKD is strongly and independently associated with mortality in patients with PAH and HF. The cardiovascular and renal systems are closely interconnected, and disruption of this balance may result in cardiorenal syndrome (CRS). Type 2 CRS refers to CKD as a consequence of chronic HF. In clinical practice, non-specific markers such as troponin, B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), and serum creatinine aid in CRS diagnosis. More specific biomarkers, including cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), galectin-3, and soluble urokinase plasminogen activator receptor (suPAR), have shown value for diagnosis and prognosis in CRS. This study aimed to evaluate comprehensively heart/kidney damage markers related to CRS in SSc patients compared with healthy controls (HC) and to examine their association with renal and cardiac ultrasound parameters. SSc patients showed significantly higher CRS markers than HC (p < 0.001). SSc patients with clinically diagnosed CRS had significantly elevated galectin-3, suPAR, sNGAL, and uNGAL levels (p < 0.05) than SSc patients without CRS. Positive correlations were found between renal resistive index (RRI) and NT-proBNP (r = 0.335, p < 0.05), and between RRI and suPAR (r = 0.331, p < 0.05). NT-proBNP, suPAR, galectin-3, sNGAL, and uNGAL emerge as promising biomarkers for the early detection of cardiac and renal involvement in SSc patients. Full article

Background: The advent and continuous improvement in antiretroviral therapy (ART) have profoundly altered the clinical course of HIV infection, shifting the focus from AIDS-related complications to the management of age-related comorbidities and non-AIDS-related hospitalizations. In this evolving context, optimizing ART is essential, with genotypic resistance testing (GRT), particularly through next-generation sequencing (NGS), playing a pivotal role. Methods: This multicenter, retrospective cross-sectional study investigated HIV-1 subtypes, resistance mutations, and drug resistance profiles among 367 people living with HIV (PLWH) in Sicily, based on 384 GRTs performed at the Microbiology Laboratory of the University Hospital of Palermo. Results: Subtype B was the most prevalent (50%), followed by circulating recombinant forms (30%). Among treatment-naïve individuals, resistance-associated mutations were infrequent, with prevalence rates of 0.4% for NRTIs, 5.5% for NNRTIs, 1.3% for PIs, and 0.8% for INIs. Conversely, treatment-experienced individuals showed significantly higher resistance rates, especially to NRTIs (16.3%), NNRTIs (10.6%), and INIs (9.6%). No significant differences in resistance patterns were observed between B and non-B subtypes. Conclusions: This study provides the first regional overview of HIV drug resistance across Sicily. Despite the detection of resistance-associated mutations, the overall prevalence of clinically relevant resistance, particularly to currently recommended therapies, remains low, especially among treatment-naïve individuals. Full article

Introduction: Urinary tract infections (UTIs) remain a significant public health issue worldwide, particularly affecting the geriatric population with increased morbidity and mortality. Aging-related immune changes, comorbidities, and urogenital abnormalities contribute to the higher incidence and complexity of UTIs in elderly patients. Antimicrobial resistance, especially extended-spectrum beta-lactamase (ESBL) production and carbapenem resistance, poses a major challenge in managing UTIs in this group. Methods: This retrospective, multicenter study included 776 patients aged 65 and older, hospitalized with a diagnosis of urinary tract infection between January 2019 and August 2024. Clinical, laboratory, and microbiological data were collected and analyzed. Urine samples were obtained under sterile conditions and pathogens identified using conventional and automated systems. Antibiotic susceptibility testing was performed according to CLSI standards. Logistic regression analyses were conducted to identify factors associated with ESBL production, carbapenem resistance, and mortality. Results: Among the patients, the median age was 78.9 years, with 45.5% female. ESBL production was detected in 56.8% of E. coli isolates and carbapenem resistance in 1.2%. Klebsiella species exhibited higher carbapenem resistance (37.8%). Independent predictors of ESBL production included the presence of urogenital cancer and antibiotic use within the past three months. Carbapenem resistance was associated with recent hospitalization, absence of kidney stones, and infection with non-E. coli pathogens. Mortality was independently associated with intensive care admission at presentation, altered mental status, Gram-positive infections, and comorbidities such as chronic obstructive pulmonary disease and urinary incontinence. Discussion: Our findings suggest that urinary pathogens and resistance patterns in elderly patients are similar to those in younger adults reported in the literature, highlighting the need for age-specific awareness in empiric therapy. The identification of risk factors for multidrug-resistant organisms emphasizes the importance of targeted antibiotic stewardship, especially in high-risk geriatric populations. Multicenter data contribute to regional understanding of resistance trends, aiding clinicians in optimizing management strategies for elderly patients with UTIs. Conclusions: This study highlights that E. coli and Klebsiella species are the primary causes of UTIs in the elderly, with resistance patterns similar to those seen in younger adults. The findings also contribute important data on risk factors for ESBL production and carbapenem resistance, supported by a robust patient sample. Full article

(1) Background: The gut microbiota plays a crucial role in chronic immune activation associated with human immunodeficiency virus (HIV) infection, acquired immune deficiency syndrome (AIDS) pathogenesis, non-AIDS-related comorbidities, and mortality among people living with HIV (PLWH). The effects of antiretroviral therapy on the microbiome remain underexplored. This study aims to map the evidence of the impact of integrase strand transfer inhibitors (INSTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) on the gut microbiota of PLWH. (2) Methods: A scoping review was conducted using PubMed, Web of Science, and Embase, with reports collected following PRISMA for Scoping Reviews (PRISMA-ScR). (3) Results: Evidence suggests that INSTI-based regimes generally promote the restoration of alpha diversity, bringing it closer to that of seronegative controls, while beta diversity remains largely unchanged. INSTI-based therapies are suggested to be associated with improvements in microbiota composition and a tendency toward reduced inflammatory markers. In contrast, NNRTI-based treatments demonstrate limited recovery of alpha diversity and are linked to an increase in proinflammatory bacteria. (4) Conclusions: Based on the review of the current literature, it is indicated that INSTI-based antiretroviral therapy (ART) therapy facilitates better recovery of the gut microbiome. Full article

Current guidelines advocate for the use of prophylactic implantable cardioverter defibrillators (ICDs) for all patients with symptomatic heart failure (HF) with low ejection fraction (EF). As many patients will never use their device and some are prone to device-related complications, scoring systems for delineating subgroups with differential ICD survival benefits are crucial to maximize ICD benefit and mitigate complications. This review summarizes the main scores, including MADIT trial-based Risk Stratification Score (MRSS) and Seattle Heart Failure Model (SHFM), which are based on randomized trials with a control group (HF medication only) and validated on large cohorts of ‘real-world’ HF patients. Recent studies using cardiac MRI (CMR) to predict ventricular arrhythmia (VA) are mentioned as well. The review shows that most scores could not delineate sustained VA incidence, but rather mortality without prior appropriate ICD therapies. Multiple scores could identify high-risk subgroups with extremely high probability of early mortality after ICD implant. On the other hand, low-risk subgroups were defined, in whom a high ratio of appropriate ICD therapy versus death without prior appropriate ICD therapy was found, suggesting significant ICD survival benefit. Moreover, MRSS and SHFM proved actual ICD survival benefit in low- and medium-risk subgroups when compared with control patients, and no benefit in high-risk subgroups, consisting of 16–20% of all ICD candidates. CMR reliably identified areas of myocardial scar and ‘channels’, significantly associated with VA. We conclude that as for today, multiple scoring models could delineate patient subgroups that would benefit differently from prophylactic ICD. Due to their modest-moderate predictability, these scores are still not ready to be implemented into clinical guidelines, but could aid decision regarding prophylactic ICD in borderline cases, as elderly patients and those with multiple co-morbidities. CMR is a promising technique which might help delineate patients with a low- versus high-risk for future VA, beyond EF alone. Lastly, genetic analysis could identify specific mutations in a non-negligible percent of patients, and a few of these mutations were found to predict an increased arrhythmic risk. Full article

The intersection of Human Immunodeficiency Virus (HIV) infection and cardiovascular disease (CVD) represents a significant area of concern; advancements in antiretroviral therapy (ART) have notably extended the life expectancy of people living with HIV (PLWH), concurrently elevating the prevalence of chronic conditions such as CVD. This paper explores the multifaceted relationship between HIV infection, ART, and cardiovascular health, focusing on the mechanisms by which HIV and ART contribute to increased cardiovascular risk, including the promotion of endothelial dysfunction, inflammation, immune activation, and metabolic disturbances. We highlight the critical roles of HIV-associated proteins—Tat, Nef, and gp120—in accelerating atherosclerosis through direct and indirect pathways that exacerbate endothelial damage and inflammation. Additionally, we address the persistent challenge of chronic inflammation and immune activation in PLWH, factors that are strongly predictive of non-AIDS-related diseases, including CVD, even in the context of effective viral suppression. The impact of ART on cardiovascular risk is examined, with particular attention to the metabolic implications of specific ART regimens, which can influence lipid profiles and body composition, thereby modifying CVD risk. The therapeutic potential of statins, aspirin, and emerging treatments such as PCSK9 inhibitors in mitigating cardiovascular morbidity and mortality among PLWH is discussed, alongside considerations for their use in conjunction with ART. Our review underscores the necessity for a comprehensive, multidisciplinary approach to cardiovascular care in PLWH, which integrates vigilant cardiovascular risk assessment and management with HIV treatment. As we navigate the evolving landscape of HIV care, the goal remains to optimize treatment outcomes while minimizing cardiovascular risk, ensuring that the gains in longevity afforded by ART translate into improved overall health and quality of life for PLWH. Full article

Objective: To determine whether HIV-infected individuals versus individuals with HIV/HCV coinfection, in the era of interferon-free therapies, exhibit an increased incidence of comorbidities and non-AIDS-related events. Methods: A retrospective analysis was conducted by collecting data from clinical records of Spanish patients at a tertiary hospital involving HIV/HCV-coinfected and HIV-infected patients, all with effectively controlled HIV. Coinfected patients underwent HCV clearance using direct-acting antivirals (DAAs) and had no history of interferon treatment. The incidences of hypertension, diabetes mellitus, cardiovascular disease, kidney disease, liver disease, non-AIDS cancer, and death were compared between the groups. Multivariate adjustments for all factors potentially impacting outcomes were used to assess the risk of clinical event onset. Propensity score (PS) analyses were also conducted to support the multivariate model results. Results: Data were available from 229 HIV/HCV-coinfected patients and 229 HIV-infected patients. Both cohorts were comparable in terms of age, gender distribution, follow-up, and HIV-related characteristics. Multivariate models and PS showed that previous exposure to HCV was not associated with the onset of any clinical events studied. Significant differences between HIV/HCV-coinfected and HIV-infected were not found for survival according to the log-rank test (p = 0.402). Conclusions: Successful HCV elimination using DAAs improved the outlook regarding comorbidities and survival across HIV/HCV-coinfected cohorts. Early HCV detection and DAA therapy could enhance clinical results. These findings provide an optimistic perspective for those living with HIV/HCV coinfection and underscore the importance of continuing efforts toward early detection and DAA treatment initiation. Full article

Background and Objectives: Antiretroviral therapy (ART) has revolutionized the management of HIV infection, transforming it from a once-debilitating disease to a chronic, manageable condition. However, challenges such as treatment resistance, medication side effects, and long-term tolerability persist, prompting the exploration of novel therapeutic approaches. We aimed to highlight the characteristics and related comorbidities of HIV/AIDS cases in which the antiretroviral therapy was modified. Material and Methods: A cross-sectional clinical investigation was conducted on adults diagnosed with HIV/AIDS who were hospitalized at the “St. Parascheva” Clinical Hospital of Infectious Diseases in Iasi in the Northeastern region of Romania. The timeframe under investigation was 1 January 2023 to 30 June 2023. Results: In the Northeastern part of Romania, from a total of 1692 patients in the active records, there were a total of 148 recorded cases of antiretroviral therapy switch in HIV-infected patients. The main reason for the ART switch was the simplification of the ART regimen (82 cases, 55.40%), viro-immunological failure (16 cases, 10.66%), other disturbances correlated to the ART regimen, dyslipidemia (34 cases 22.97%), depression (3 cases, 2.02%), suicide attempt (1 case, 0.67%), new situations, including the appearance of pregnancy (3 cases 2.02%), and tuberculosis (9 cases, 6.08%). ART before the switch was represented by protease inhibitors that accounted for 84 cases (56.75%) of the ART switch. Following the therapy switch, integrase inhibitor-based ART single-tablet regimens accounted for 43.91% (65 cases) of all changeovers, with non-nucleoside reverse transcriptase inhibitor regimens coming in second, in 63 cases, 42.66%. Conclusions: ART switch as an experimental therapy offers a promising approach to optimizing HIV treatment outcomes. By focusing on viral suppression and immune reconstitution, addressing treatment challenges, and exploring novel ARV agents, ART switch strategies aim to improve the overall health and well-being of individuals living with HIV. Full article

Objectives: post-stroke depression (PSD), cognitive impairment, and sleep disturbances are the most common post-stroke conditions. To aid clinical practice for a highly confounded clinical problem, a clearer understanding of the associations between comorbid PSD, post-stroke cognitive impairment, and sleep disturbances is necessary. Materials and Methods: a scoping review of the literature was conducted according to the recommended guidelines using the search term [“stroke (mesh term) AND depression (in the abstract) AND cognitive (in the abstract) AND sleep (in the abstract)”]. Results: 10 studies met the criteria for inclusion. Only one study reported a co-occurrence of post-stroke emotional distress and sleep disturbances at a rate of 10.7%. Poor sleep and cognitive impairment are independent risk factors for PSD. The relationship between post-stroke poor sleep and cognitive impairment is ambiguous. None of the studies examined how PSD, cognitive impairment, and sleep disturbances interact to influence stroke outcomes. Conclusions: the dearth of studies indicates either a lack of awareness of the potential relationship between the three outcomes and the possible range of inter-related non-motor outcomes after stroke or the practical challenges in designing appropriate studies. The included studies had methodological weaknesses in their observational design and use of imprecise, subjective outcome measurements. Important knowledge gaps are identified for future research. Full article

Despite cancer being a leading comorbidity amongst individuals with HIV, there are limited data assessing cancer trends across different antiretroviral therapy (ART)-eras. We calculated age-standardised cancer incidence rates (IRs) from 2006–2021 in two international cohort collaborations (D:A:D and RESPOND). Poisson regression was used to assess temporal trends, adjusted for potential confounders. Amongst 64,937 individuals (31% ART-naïve at baseline) and 490,376 total person-years of follow-up (PYFU), there were 3763 incident cancers (IR 7.7/1000 PYFU [95% CI 7.4, 7.9]): 950 AIDS-defining cancers (ADCs), 2813 non-ADCs, 1677 infection-related cancers, 1372 smoking-related cancers, and 719 BMI-related cancers (groups were not mutually exclusive). Age-standardised IRs for overall cancer remained fairly constant over time (8.22/1000 PYFU [7.52, 8.97] in 2006–2007, 7.54 [6.59, 8.59] in 2020–2021). The incidence of ADCs (3.23 [2.79, 3.72], 0.99 [0.67, 1.42]) and infection-related cancers (4.83 [4.2, 5.41], 2.43 [1.90, 3.05]) decreased over time, whilst the incidence of non-ADCs (4.99 [4.44, 5.58], 6.55 [5.67, 7.53]), smoking-related cancers (2.38 [2.01, 2.79], 3.25 [2.63–3.96]), and BMI-related cancers (1.07 [0.83, 1.37], 1.88 [1.42, 2.44]) increased. Trends were similar after adjusting for demographics, comorbidities, HIV-related factors, and ART use. These results highlight the need for better prevention strategies to reduce the incidence of NADCs, smoking-, and BMI-related cancers. Full article

The evolution of antiretroviral therapies (ART) has tremendously improved the life expectancy of people living with human immunodeficiency virus (HIV) (PLWH), which is currently similar to the general population. However, as PLWH are now living longer, they exhibit various comorbidities such as a higher risk of cardiovascular disease (CVD) and non-acquired immunodeficiency syndrome (AIDS)-defined malignancies. Clonal hematopoiesis (CH) is the acquisition of somatic mutations by the hematopoietic stem cells, rendering them survival and growth benefit, thus leading to their clonal dominance in the bone marrow. Recent epidemiologic studies have highlighted that PLWH have a higher prevalence of CH, which in turn is associated with increased CVD risk. Thus, a link between HIV infection and a higher risk for CVD might be explained through the induction of inflammatory signaling in the monocytes carrying CH mutations. Among the PLWH, CH is associated with an overall poorer control of HIV infection; an association that requires further mechanistic evaluation. Finally, CH is linked to an increased risk of progression to myeloid neoplasms including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), which are associated with particularly poor outcomes among patients with HIV infection. These bidirectional associations require further molecular-level understanding, highlighting the need for more preclinical and prospective clinical studies. This review summarizes the current literature on the association between CH and HIV infection. Full article