Search Results (789)

Background/Objectives: Opportunistic fungal infections are common among people living with HIV (PLHIV) and contribute substantially to morbidity, mortality, and hospitalization rates in this population. This study aimed to determine the prevalence of dermatological manifestations of fungal infections in HIV-positive patients and examine their association with demographic, clinical, and immunological characteristics. Methods: A retrospective review of medical records from 2500 PLHIV treated at the Infectious Diseases Unit of “Andreas Syggros” Hospital for Skin and Venereal Diseases between 1988 and 2017. Data from patients diagnosed with opportunistic fungal infections were analyzed. Participants were classified as either antiretroviral therapy (ART)-naïve or already receiving treatment. Recorded fungal infections were correlated with epidemiological variables and CD4+ T-cell counts. Results: Opportunistic fungal infections were identified in 859 patients (34.36%), with a marked male predominance. Candidiasis was the most frequently reported condition, with a higher prevalence among female patients. Lower CD4+ counts were significantly associated with an increased risk of cryptococcal meningitis, esophageal candidiasis, Pneumocystis jirovecii pneumonia (PJP), and oral candidiasis, whereas higher CD4+ counts were more common in patients with dermatophytosis, onychomycosis, and pityriasis/tinea versicolor. Conclusions: Opportunistic fungal infections remain highly prevalent in PLHIV, particularly among those with advanced immunosuppression. CD4+ T-cell counts are key diagnostic and prognostic markers, reinforcing their importance in monitoring disease progression and guiding clinical management. Full article

The identification of recent HIV infections among newly diagnosed HIV cases is relevant to both implementing targeted prevention measures and estimating HIV incidence. We analyzed data on new HIV diagnoses in Italy from 2012 to 2023. We selected cases that were tested by at least one of three criteria (test for HIV recency, data on HIV seroconversion, clinical signs of acute HIV infection) to assess the rate of recent (<1 year) HIV infections. We analyzed these cases by gender, age group, nationality, and mode of transmission, and revaluated cases that were initially scored as a late diagnosis but then classified as a recent infection. Out of 36,289 new HIV diagnoses, 17,558 (48.8%) were tested for recent infection by at least one criterion and 3772 (21.5%) were classified as recent. At multivariate analysis, the probability of being recently infected was significantly higher among males, people aged 15–44 years, Italians, individuals diagnosed in Northern and Central Italy, heterosexual males, MSM, and people with a CD4 count ≥ 350 cells/uL at diagnosis. Of 8658 cases initially classified as late diagnoses, 979 (11.3%) were reclassified as recent by the aforementioned criteria. Monitoring recent infections among new HIV diagnoses is beneficial to individuals—because it motivates recently infected people to comply with antiretroviral treatment (which is more effective if started early) and to collaborate to partner notification, and to public health, as it provides evidence of epidemiological changes and stresses the need for targeted prevention in well-defined populations at risk. 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

Candidemia is a highly prevalent invasive fungal infection caused primarily by C. albicans, C. parapsilosis, C. glabrata (currently Nakaseomyces glabratus), C. tropicalis, and C. krusei (currently Pichia kudriavzevii). Risk factors for the development of candidemia include steroid-induced immunosuppression used in solid organ or hematopoietic transplantation, and neutropenia secondary to infectious or tumorous processes. Alterations in the gut microbiota in people living with HIV, caused by antiretroviral therapy, increase the possibility of colonization by C. albicans. Likewise, the presence of a central venous catheter, parenteral nutrition, and abdominal surgery stand out as the main risk factors for the development of candidemia. New diagnostic tools have been developed for the diagnosis of this mycosis that allow the identification of the main species, from improvements in conventional stains such as calcofluor white, which increases sensitivity, as well as technologies such as T2 Candida, MoiM assay, biomarker panel (1,3 β-D-glucan, C-reactive protein, presepsin, and procalcitonin), and, more recently, the development of biosensors for the identification of Candida spp. Regarding treatment, the use of micafungin and anidulafungin in patients with obesity defined by a BMI > 30 kg/m² has shown higher survival rates and therapeutic success. Meanwhile, newer antifungals such as rezafungin and fosmanogepix have demonstrated excellent results in the treatment of these patients. Therefore, this review aims to update the epidemiology and risk factors of candidemia, as well as analyze the diagnostic tools and treatments currently available. Full article

The use of long-acting cabotegravir and rilpivirine (LA CAB/RPV) is a novel approach to manage human immunodeficiency virus (HIV). This injectable regimen offers benefits such as an improved quality of life, reduced stigma and enhanced treatment satisfaction by minimising the need for daily medication adherence. This review summarises the findings of clinical trials and real-world studies on the safety, tolerability and metabolic effects of LA CAB/RPV, which are areas that have received less extensive coverage in previous reviews. Clinical trial data suggest that LA CAB/RPV is generally safe and well tolerated. The most common side effects were injection site reactions, affecting 70–97% of participants. However, these were typically mild and short lived, rarely leading to treatment discontinuation in fewer than 2–3% of cases. Systemic side effects were minimal and comparable to those observed with traditional oral antiretroviral therapy. Real-world studies corroborated these findings, reporting low discontinuation rates due to adverse events. Regarding metabolic impact, clinical trials showed minimal weight gain (an average increase of 1–2 kg over 48–96 weeks) with no significant differences or impact on lipid and glucose levels. Although real-world data are still emerging, they suggest similar trends, including a possible improvement in lipid profiles. Overall, LA CAB/RPV appears to be a safe, well-tolerated and effective treatment option, although longer-term follow-up is needed. Full article

Objective: To characterize the profiles of resistance mutations to HIV reverse transcriptase inhibitors in Gabon. Design: Cross-sectional study conducted over 37 months, from October 2019 to October 2022, at the IST/HIV/AIDS Reference Laboratory, a reference center for the biological monitoring of people living with the human immunodeficiency virus (PWHIV) in Gabon. Methods: Plasma from 666 PWHIV receiving antiretroviral treatment was collected, followed by RNA extraction, amplification, and reverse transcriptase gene sequencing. Statistical analyses were performed using Stata^® 14.0 software (USA). Results: Six hundred and sixty-six (666) PWHIV plasma collected from 252 male and 414 female patients were analyzed and 1654 mutations were detected in 388 patients, including 849 (51.3%) associated with nucleoside reverse transcriptase inhibitors (NRTIs) and 805 (48.7%) with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Three of the most prescribed treatment regimens were associated to the appearance of both NRTIs and NNRTIs resistance mutations: TDF + 3TC + EFV (24.02%; 160/666); TDF + FTC + EFV) (17.2%; 114/666) and AZT + 3TC + EFV (14.6%; 97/666). Additionally, stage 3 of CD4 T-lymphocyte deficiency, the higher viral load, and treatment duration are risk factors influencing the appearance of virus mutations. Also, treatment containing TDF-3TC + DTG is more protective against mutations. Conclusions: Drug resistance mutations are common in Gabon and compromise the efficacy of ART. Further study must search for other causes of therapeutic failure in Gabon in PWHIV. Full article

This review critically examines the recent advancements in the development and application of electrospun molecularly imprinted polymer (MIP) nanofiber membranes for environmental remediation. Emphasizing the significance of these materials, the discussion highlights the mechanisms by which electrospun MIPs achieve high selectivity and efficiency in removing various pollutants, including dyes, heavy metals, and pharmaceutical residues such as NSAIDs and antiretroviral drugs. The synthesis methodologies are explored in detail, focusing on the choice of monomers, templates, and polymerization conditions that influence the structural and functional properties of the membranes. Characterization techniques used to assess morphology, surface area, porosity, and imprinting efficacy are also examined, providing insights into how these parameters affect adsorption performance. Furthermore, the review evaluates the performance metrics of electrospun MIPs, including adsorption capacities, selectivity, reusability, and stability in complex environmental matrices. Practical considerations, such as scalability, regeneration, and long-term operational stability, are discussed to assess their potential for real-world applications. The article concludes with an outline of future research directions, emphasizing the need for multi-template imprinting, integration with existing treatment technologies, and field-scale validation to address current limitations. Full article

Background and Objectives: Long-acting cabotegravir and rilpivirine (LA-CAB/RPV) offers an alternative to daily oral antiretroviral therapy (ART) for people living with HIV (PLWH). Although LA-CAB/RPV has been approved in Turkey, the country remains in the pre-rollout period, and national data on patient perspectives are lacking. This is the first nationwide study from Turkey, a setting of increasing HIV incidence, assessing PLWH perspectives on switching to LA-CAB/RPV and the influence of motivational factors on treatment preferences. Materials and Methods: A prospective, multicenter, cross-sectional study was conducted across 11 HIV treatment centers representing all regions of Turkey. Virologically suppressed PLWH meeting current eligibility criteria for LA-CAB/RPV were included. Treatment preferences (switch to LA-CAB/RPV or remain on oral ART) and five anticipated motivational domains, namely perceived efficacy, safety, convenience, privacy, and cost, were systematically assessed through structured, face-to-face interviews. Results: Among 200 eligible participants, 86% (n = 172) preferred switching to LA-CAB/RPV. In all subgroups, LA-CAB/RPV was preferred over oral ART, except for those with no formal literacy. Prior awareness of LA-CAB/RPV was significantly associated with the switching preference (p < 0.001), with healthcare providers being the most common source of information, at 45.5% (n = 172) (p < 0.001). Residential proximity to the healthcare center (p = 0.018) and all motivational factors significantly influenced the preference (p < 0.05). Notably, when participants who initially chose to remain on oral ART were asked whether they would reconsider switching if injections were administered every six months, overall preference for long-acting therapy increased from 86% to 98%. Conclusions: High clinical eligibility and strong acceptability for LA-CAB/RPV were observed among Turkish PLWH. Our findings demonstrate that structured motivational factors significantly influence the treatment preference. Addressing these patient-centered factors and logistical barriers may support the successful integration of long-acting therapies into routine HIV care. Future longer-interval agents may improve patient-centered acceptability. Full article

Background/Objectives: Restored CD4 absolute counts (CD4AC) and CD4/CD8 ratio in the setting of continuous antiretroviral treatment (ART) do not exclude a low-level immune activation associated with HIV reservoirs, microbial translocation, or the side effects of ART itself, which accelerates the aging of people living with HIV (PLHIV). To delineate biomarkers of incomplete immune restoration in PLHIV on successful ART, we evaluated T-lymphocyte mitochondrial parameters in relation to phenotypic markers of immune exhaustion and senescence. Methods: PLHIV with sustained viral suppression, CD4AC > 500 and CD4/CD8 ratio >0.9 on ART (n = 39) were compared to age-matched ART-naïve donors (n = 27) and HIV(–) healthy controls (HC, n = 35). CD4 and CD8 differentiation and effector subsets (CCR7/CD45RA and CD27/CD28), activation, exhaustion, and senescence markers (CD38, CD39 Treg, CD57, TIGIT, and PD-1) were determined by flow cytometry. Mitochondrial mass (MM) and membrane potential (MMP) of CD8 and CD4 T cells were evaluated with MitoTracker Green and Red flow cytometry dyes. Results: ART+PLHIV differed from HC by increased CD4 TEMRA (5.3 (2.1–8.8) vs. 3.2 (1.6–4.4), p < 0.05), persistent TIGIT+CD57–CD27+CD28– CD8+ subset (53.9 (45.5–68.9) vs. 40.1 (26.7–58.5), p < 0.05), and expanding preapoptotic TIGIT–CD57+CD8+ effectors (9.2 (4.3–21.8) vs. 3.0 (1.5–7.3), p < 0.01) in correlation with increased CD8+ MMP (2527 (1675–4080) vs.1477 (1280–1691), p < 0.01). These aberrations were independent of age, time to ART, or ART duration, and were combined with increasing CD4 T cell MMP and MM. Conclusions: In spite of recovered CD4AC and CD4/CD8 ratio, the increased CD8+ MMP, combined with elevated markers of exhaustion and senescence in ART+PLHIV, signals a malfunction of the CD8 effector pool that may compromise viral reservoir latency. Full article

The HIV-1 aspartic protease is an effective target for the treatment of HIV/AIDS. Current therapy utilizes a selection of nine protease inhibitors (PIs) in combination with other classes of antiretroviral drugs. Although PIs were originally developed based on the knowledge of the HIV-1 subtype B protease, the existence of other HIV-1 subtypes and the effects of drug resistance on currently available PIs have become a major challenge in the treatment of HIV/AIDS. Specifically, the HIV-1 subtype C accounts for more than half of the global HIV infections. Considering the importance and relevance of the subtype C virus, in this timely review we discuss the effect of polymorphisms in the HIV-1 subtype C protease on drug resistance, flap flexibility, and hinge region dynamics. We discuss novel paradigms of protease inhibition that attempt to overcome the limitations of currently available inhibitors which fall short considering genetic diversity and resistance mutations. Full article

Background/Objectives: The timely initiation of antiretroviral therapy (ART) in persons living with HIV (PLWH) can improve clinical outcomes. However, ART commencement is often delayed. Portugal, despite having one of the highest new HIV diagnosis rates within the European Union, has limited available national-level data. Prior evidence from 2017 to 2018 suggests that the average time to ART initiation exceeds the recommendations for optimal patient benefits. This study aimed to determine the number of days from the first hospital appointment to the commencement of ART among newly diagnosed PLWH in Portugal between 2017 and 2022 at the national level and across different hospitals. It was hypothesized that newly diagnosed PLWH in Portugal experience a delay in ART initiation beyond the recommended timeframe. Methods: A retrospective analysis of records from Portuguese public tertiary care hospitals, which manage most HIV patients, was conducted. Descriptive statistics (measures of central tendency, dispersion, and frequency) were applied, along with association tests and a binary logistic regression model to examine factors influencing the timing of ART initiation. Results: A total of 2229 cases (out of 3434 received) from 19 hospitals were considered eligible. The median time interval between the first hospital appointment and ART initiation was 29.00 days, with a decreasing tendency between 2017 and 2022. Patients initiating therapy after 14 days had higher CD4 levels and lower viral loads compared to those starting within 14 days, with statistical significance. Conclusions: Continuous and regular monitoring of key indicators, such as the time to ART initiation, is pivotal for assessing the effectiveness of HIV treatment programs and pinpointing areas in need of improvement. Full article

Treatment for HIV infection has become more manageable due to advances in combination antiretroviral therapy (cART). However, HIV still significantly affects the central nervous system (CNS) in infected individuals, even with effective plasma viral suppression, due to persistent viral reservoirs and chronic neuroinflammation. This ongoing inflammation contributes to the development of HIV-associated neurocognitive disorders (HANDs), including dementia and Alzheimer’s disease-like pathology. These complications are particularly prevalent among the aging population with HIV. This review aims to provide a comprehensive overview of HAND, with a focus on the contribution of oxidative stress induced by HIV-mediated reactive oxygen species (ROS) production through viral proteins such as gp120, Tat, Nef, Vpr, and reverse transcriptase. In addition, we discuss current and emerging therapeutic interventions targeting HAND, including antioxidant strategies and poly (ADP-ribose) polymerase (PARP) inhibitors. These are potential adjunctive approaches to mitigate neuroinflammation and oxidative damage in the CNS. 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

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