Tenofovir-Associated Kidney Dysfunction and Bone Fracture: A Case Report and Literature Review.

Tenofovir is an integral part of antiretroviral therapy used to treat HIV. Long-term use of tenofovir has been associated with decreased glomerular filtration rate, leading to chronic kidney disease, as well as acidosis, electrolyte imbalances, and tubular dysfunction. Tenofovir can also disrupt bone health by decreasing renal phosphate absorption, contributing to osteomalacia. This leads to disruption in mineral metabolism, elevated parathyroid hormone levels, and ultimately, low bone mineral density. Replacing tenofovir with alternative antiretroviral therapy can improve kidney function if done early in the course of the disease. Here, we discuss a case of a 65-year-old woman with HIV who presented with advanced renal failure and hypophosphatemia-induced bone fracture attributed to long-term use of tenofovir. We conclude monitoring kidney function and considering alternative antiretroviral therapy is important to prevent and manage these side effects in patients on long-term tenofovir therapy.

Exploring salivary metabolome alterations in people with HIV: towards early diagnostic markers.

Background: The human immunodeficiency virus (HIV) remains a critical global health issue, with a pressing need for effective diagnostic and monitoring tools. Methodology: This study explored distinctions in salivary metabolome among healthy individuals, individuals with HIV, and those receiving highly active antiretroviral therapy (HAART). Utilizing LC-MS/MS for exhaustive metabolomics profiling, we analyzed 90 oral saliva samples from individuals with HIV, categorized by CD4 count levels in the peripheral blood. Results: Orthogonal partial least squares-discriminant analysis (OPLS-DA) and other analyses underscored significant metabolic alterations in individuals with HIV, especially in energy metabolism pathways. Notably, post-HAART metabolic profiles indicated a substantial presence of exogenous metabolites and changes in amino acid pathways like arginine, proline, and lysine degradation. Key metabolites such as citric acid, L-glutamic acid, and L-histidine were identified as potential indicators of disease progression or recovery. Differential metabolite selection and functional enrichment analysis, combined with receiver operating characteristic (ROC) and random forest analyses, pinpointed potential biomarkers for different stages of HIV infection. Additionally, our research examined the interplay between oral metabolites and microorganisms such as herpes simplex virus type 1 (HSV1), bacteria, and fungi in individuals with HIV, revealing crucial interactions. Conclusion: This investigation seeks to contribute understanding into the metabolic shifts occurring in HIV infection and following the initiation of HAART, while tentatively proposing novel avenues for diagnostic and treatment monitoring through salivary metabolomics.

Point prevalence of metabolic syndrome in HIV positive patients.

Introduction: Human immunodeficiency virus (HIV)-related morbidity and mortality have declined over time, but this increased longevity may lead to the development of other diseases, which may further manifest as the metabolic syndrome (MS). Method: To find out the point prevalence of MS in HIV positive patients, a cross-sectional prospective observational study was conducted on 200 patients who approached ART plus Centre of Government Medical College and Hospital Jammu, including 50 symptomatic patients HIV negative as controls. Results: The mean age group in MS was 37.85 ± 6.61. Males consisted of 55% (110) and females consisted of 45% (90). The overall prevalence of MS was 13.5%, with prevalence in males being 16.3% and in females 10%. Patients receiving first line highly active antiretroviral therapy (HAART) showed a 24% prevalence, while that of second line HAART showed a 14% prevalence. Central obesity (47.3%) was the most common component of MS followed by hyperglycemia (43.3%), hypertriglyceridemia (38.6%), and low high density cholesterol (HDL-C) level (38.6%). Out of 84 males with MS, 94% (79) males were having hypertriglyceridemia, 88% (74) were hypertensive, and 72% (60) were having FBS >=100. Out of 66 females with MS, 100% (66) females had central obesity and 88% (58) had hypertriglyceridemia and low HDL-C levels. Conclusion: The metabolic complications as a result of treatment with HAART leave HIV patients at a risk of developing cardiovascular disease and diabetes in spite of improvements in morbidity and mortality. Risk factors like central obesity, hypertension, hyperglycemia, and hypertriglyceridemia should be taken into consideration well before to prevent the add-on effect of developing MS.

NEDA-3 achievement in early highly active relapsing remitting multiple sclerosis patients treated with Ocrelizumab or Natalizumab.

BACKGROUND: in the early stages of Multiple Sclerosis (MS), initiating high-efficacy disease-modifying therapy (HE DMTs) may represent an optimal strategy for delaying neurological damage and long-term disease progression, especially in highly active MS patients (HAMS). Natalizumab (NAT) and Ocrelizumab (OCR) are recognized as HE DMTs with significant anti-inflammatory effects. This study investigates NEDA-3 achievement in treatment-naïve HAMS patients receiving NAT or OCR over three years. METHODS: we retrospectively enrolled treatment-naïve HAMS patients undergoing NAT or OCR, collecting demographic, clinical, and instrumental data before and after treatment initiation to compare with propensity score analysis disease activity, time to disability worsening, and NEDA-3 achievement. RESULTS: we recruited 281 HAMS patients with a mean age of 32.7 years (SD 10.33), treated with NAT (157) or OCR (124). After three years, the Kaplan-Meier probability of achieving NEDA-3 was 66.0 % (95 % CI: 57.3 % - 76.0 %) with OCR and 68.2 % (95 % CI: 59.9 % - 77.7 %) with NAT without significant differences between the two groups (p = 0.27) DISCUSSION AND CONCLUSION: starting HE DMT with monoclonal antibodies for HAMS could achieve NEDA-3 in a high percentage of patients without differences between NAT or OCR.

Estimated Pulse Wave Velocity as a Novel Non-Invasive Biomarker for Metabolic Syndrome Among People Living with HIV.

Purpose: This study aims to investigate the relationship between estimated pulse wave velocity (ePWV) and metabolic syndrome (MetS) in people living with HIV (PLWH), proposing a novel and convenient predictor for early detection of MetS in PLWH. Patients and Methods: A total of 485 PLWH were enrolled. These participants were categorized into two groups based on the estimated pulse wave velocity (ePWV) level. Demographic and clinical data were collected to investigate the correlation between ePWV and MetS. Results: The cohort of 485 PLWH was categorized into high-ePWV and low-ePWV groups based on ePWV cutoff value of 10 m/s. We observed significant differences in components of MetS including triglycerides (TG, P < 0.05), HDL cholesterol (HDL-C, P < 0.01), systolic blood pressure (SBP, P < 0.001), diastolic blood pressure (DBP, P < 0.05), and fasting plasma glucose (FPG, P < 0.001) between the two groups. Furthermore, we employed receiver operating characteristic (ROC) curves to demonstrate the effectiveness of ePWV as a predictive indicator for MetS in PLWH (AUC = 0.739, P < 0.001). According to the ROC curve, the optimal cut-off value of ePWV was 7.4 m/s, and its sensitivity and specificity in diagnosing MetS in PLWH were 79.03% and 64.07%, respectively. Although the 7.4 m/s cutoff increased the false positive rate compared to the traditional cutoff, it significantly reduced the rate of missed diagnoses, effectively identifying 79.03% of PLWH with MetS. Conclusion: ePWV is a non-invasive and convenient novel biomarker with predictive capabilities for MetS in PLWH.

Selection of disease modifying therapies in multiple sclerosis based on patient's age and disease activity: Data from a nationwide registry.

BACKGROUND: Knowledge of the safety and efficacy of disease-modifying therapies (DMTs) in older patients with Multiple Sclerosis (pwMS) is limited due to their exclusion from clinical trials. Our purpose is to evaluate the choice of DMTs in pwMS older than 50 years old in a real-world setting. METHODS: Cross-sectional study of pwMS from the Argentine MS and NMOSD Registry. We included patients under 35 and above 50 years old prescribed DMTs. Disease activity was categorized as highly active (HA) or not highly active (NHA), and DMTs were classified as low efficacy therapies (LET) or high efficacy therapies (HET). RESULTS: 1460 patients (65% females) were enrolled. The HA group comprised 241 patients, 198 young (82.2%) and 43 older (17.8%). The NHA group included 1219 patients, 893 young (73%) and 326 older (27%). In the NHA group, older patients received LET more frequently than younger patients (66% versus 44%; p < 0.01). In the HA group, older patients received LET in 61% of cases, whereas younger patients received HET in 71% (p = 0.01). CONCLUSION: The study shows the preference of LET in older patients regardless of disease activity. However it does not demonstrate a difference in disability in older patients based on low vs high efficacy DMTs used, probably due to the design of the study. Further longitudinal studies are warranted to address this issue.

Cryptosporidium-induced acute kidney injury in a patient with acquired immunodeficiency syndrome.

Cryptosporidium is a pathogen that can cause infectious enteritis especially in immunocompromised patients. Acute kidney injury, electrolyte imbalance, and acid-base disorders may occur as a result of high volumes of intestinal fluid loss, which has not been previously reported to be a common manifestation of cryptosporidiosis. Numerous antigen detection methods can be used to ensure early diagnosis of Cryptosporidium infection, which is crucial to prevent morbidities. We report a unique case of cryptosporidiosis in a 33-year-old male patient with acute kidney injury and profound hypokalemia, hyponatremia, hypocalcemia, hypophosphatemia, hypomagnesemia, and metabolic acidosis. Following the initiation of antiretroviral therapy to human immunodeficiency virus, the patient's symptoms improved and he recovered fully from kidney injury and electrolyte imbalance, highlighting the importance of early antiretroviral therapy.

Hepatitis C virus eradication in people living with human immunodeficiency virus: Where are we now?

Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV, according to World Health Organization. People living with HIV (PLWH) are six times greater affected by HCV, compared to HIV negative ones; the greater prevalence is encountered among people who inject drugs and men who have sex with men: the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection. These patients experience a high rate of chronic hepatitis, which if left untreated progresses to end-stage liver disease and hepatocellular carcinoma (HCC) HIV infection increases the risk of mother to child vertical transmission of HCV. No vaccination against both infections is still available. There is an interplay between HIV and HCV infections. Treatment of HCV is nowadays based on direct acting antivirals (DAAs), HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono- and coinfected individuals, especially when used at an early stage of fibrosis, reducing liver disease mortality and morbidity. Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication, the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV. HCV eradication can determine dyslipidemia, since HCV promotes changes in serum lipid profiles and may influence lipid metabolism. In addition to these apparent detrimental effects on the lipid profile, the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function. The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.

Case report: A highly active refractory myasthenia gravis with treatment of telitacicept combined with efgartigimod.

There is always a lack of effective treatment for highly active refractory generalized myasthenia gravis (GMG). Recently, telitacicept combined with efgartigimod significantly reduces circulating B cells, plasma cells, and immunoglobulin G, which brings promising therapeutic strategies. We report a case of a 37-year-old female patient with refractory GMG, whose condition got significant improvement and control with this latest treatment after multiple unsuccessful therapies of immunosuppressants. The new combination deserves further attention in the therapeutic application of myasthenia gravis.

Prevalence and incidence of anal high-grade squamous intraepithelial lesions in a cohort of cisgender men and transgender women who have sex with men diagnosed and treated during acute HIV acquisition in Bangkok, Thailand.

INTRODUCTION: Men who have sex with men (MSM), especially those living with HIV, are at an increased risk of anal cancer. The prevalence and incidence of its precursor, anal high-grade squamous intraepithelial lesions (HSILs), among MSM who started antiretroviral therapy during acute HIV acquisition are yet to be explored. METHODS: Participants in an acute HIV acquisition cohort in Bangkok, Thailand, who agreed to take part in this study, were enrolled. All participants were diagnosed and started antiretroviral therapy during acute HIV acquisition. Human papillomavirus (HPV) genotyping and high-resolution anoscopy, followed by anal biopsy as indicated, were done at baseline and 6-monthly visits. RESULTS: A total of 89 MSM and four transgender women were included in the analyses. Median age at enrolment was 26 years. Baseline prevalence of histologic anal HSIL was 11.8%. With a total of 147.0 person-years of follow-up, the incidence of initial histologic anal HSIL was 19.7 per 100 person-years. Factors associated with incident anal HSIL were anal HPV 16 (adjusted hazards ratio [aHR] 4.33, 95% CI 1.03-18.18), anal HPV 18/45 (aHR 6.82, 95% CI 1.57-29.51), other anal high-risk HPV (aHR 4.23, 95% CI 1.27-14.14), syphilis infection (aHR 4.67, 95% CI 1.10-19.90) and CD4 count <350 cells/mm3 (aHR 3.09, 95% CI 1.28-7.48). CONCLUSIONS: With antiretroviral therapy initiation during acute HIV acquisition, we found the prevalence of anal HSIL among cisgender men and transgender women who have sex with men to be similar to those without HIV. Subsequent anal HSIL incidence, although lower than that of those with chronic HIV acquisition, was still higher than that of those without HIV. Screening for and management of anal HSIL should be a crucial part of long-term HIV care for all MSM.

Biological Depiction of Lipodystrophy and Its Associated Challenges Among HIV AIDS Patients: Literature Review.

Lipodystrophy syndrome is a medical condition characterized by the absence of adipose tissue without any underlying starvation or macromolecule breakdown. In HIV AIDS patients, the use of highly active antiretroviral therapy (HAART) can lead to an acquired form of lipodystrophy, with a prevalence ranging from 10% to 83% among HIV AIDS patients. It was aimed to review the current understanding of biological depiction and challenges related to lipodystrophy in AIDS patients. Relevant articles published in the English language were searched in PubMed, Google Scholar, and Google. Keywords used for the search were: lipodystrophy, lipodystrophy and HIV, ART and lipodystrophy, HIV treatment, metabolic syndrome and HIV. Articles with full abstract information were read for those that met the objective criteria of the review, then full text of the articles was accessed and used. It was revealed by the literature that patients who developed lipodystrophy are characterized by insulin abnormality, obesity, diabetes mellitus, dyslipidemia, fatty liver disease, and ovarian dysfunction. Anthropometric measurements have been known to change significantly with lipodystrophy. HIV patients suffering from hepatitis C virus, hepatitis B virus, who take a protease inhibitor, are changing treatment or duration of treatment, and are women are the common risk factors for lipodystrophy. The metabolic syndrome seen in HIV patients associated with lipodystrophy can further be complicated to different adverse health effects and can result in increased morbidity and mortality rate if not treated. Existing studies have successfully identified several challenges faced by HIV AIDS patients due to lipodystrophy, including low self-esteem, compromised quality of life, and poor treatment adherence. However, it is crucial to acknowledge that there may be numerous other challenges that have yet to be discovered, emphasizing the need for further studies. It is recommended that managing dyslipidemia, treating diabetes mellitus, modifying lifestyle, and improving the anthropometric measurements have crucial roles to halt further complications associated with lipodystrophy.

Bone Disease in HIV: Need for Early Diagnosis and Prevention.

The transformation of HIV into a manageable chronic condition has unveiled new clinical challenges associated with aging-related pathologies, including bone disease. This review explores the intricate relationship between HIV, antiretroviral therapy (ART), and bone disease, highlighting the necessity of early diagnosis and preventative strategies to mitigate the increased risk of osteopenia, osteoporosis, and fractures in people living with HIV (PLWHIV). It synthesizes the current literature to elucidate the multifactorial etiology of bone pathology in this population, that includes direct viral effects, chronic immune activation, ART-associated risks, and the impact of traditional risk factors for bone loss. Through a critical examination of modern diagnostic methods, lifestyle modifications, evidence-based preventive actions, and pharmacological treatments, the necessity for comprehensive management is highlighted, along with recommendations for integrated healthcare approaches vital for achieving optimal patient outcomes. By advocating for a proactive, patient-centered, and multidisciplinary strategy, this review proposes a plan to integrate bone health into standard HIV care through active risk identification, vigilant screening, effective preventive measures, tailored treatments, and informed decision-making, in an effort to ultimately enhance the quality of life for PLWHIV.

A systematic review assessing the potential use of cystatin c as a biomarker for kidney disease in people living with HIV on antiretroviral therapy.

The introduction of antiretroviral therapy (ART) has significantly prolonged the lifespan of people living with human immunodeficiency virus (PLWH). However, the sustained use of this drug regimen has also been associated with a cluster of metabolic anomalies, including renal toxicity, which can lead to the development of kidney diseases. In this study, we reviewed studies examining kidney disease in PLWH sourced from electronic databases such as PubMed/MEDLINE, Scopus, and Google Scholar, as well as gray literature. The narrative synthesis of data from these clinical studies demonstrated that the serum levels of cystatin C remained unchanged or were not affected in PLWH on ART, while the creatinine-based glomerular filtration rate (GFR) fluctuated. In fact, some of the included studies showed that the creatinine-based GFR was increased in PLWH taking tenofovir disoproxil fumarate-containing ART, perhaps indicating that the use of both cystatin C- and creatinine-based GFRs is vital to monitor the development of kidney disease in PLWH. Clinical data summarized within this study indicate the potential detrimental effects of tenofovir-based ART regimens in causing renal tubular injury, while highlighting the possible beneficial effects of dolutegravir-based ART on improving the kidney function in PLWH. However, the summarized literature remains limited, while further clinical studies are required to provide insights into the potential use of cystatin C as a biomarker for kidney disease in PLWH.

Analysis of antiretroviral therapy interruption in people living with HIV during the 2010-2021 Period. / [Artículo traducido] Análisis de la interrupción de la terapia antirretroviral en personas que viven con VIH/sida durante el periodo 2010­2021.

OBJECTIVE: In the context of the advancement of antiretroviral therapy and, as the characteristics of people living with HIV progress toward an aging population, understanding the causes of treatment interruption becomes crucial. The aim of the study was to determine the change in reasons for antiretroviral treatment discontinuation for 12 years. Secondarily, compare annual antiretroviral regimen discontinuation rate and factors associated. METHODS: We conducted an analysis using data from people living with HIV who were receiving antiretroviral therapy and discontinued it for any reason. The study included people with HIV infection who visited an outpatient hospital pharmacy clinic from January 2010 to December 2021. Two periods were differentiated for the analysis: 2010-2015 and 2016-2021. The reasons for antiretroviral treatment discontinuation followed classification described by Swiss cohort. In the context of this study, it is pertinent to note that the term 'interruption' will be consistently used in this article to refer to the act of switching or stopping antiretroviral treatment. To examine factors associated with antiretroviral therapy discontinuation, we utilized Kaplan-Meier methods and Cox proportional models. RESULTS: We included 789 people living with HIV, predominantly male (81,5%). The main reason for discontinuation was clinical decision (50.2%) followed by adverse effects (37.9%). Focusing on clinical decision, we observed a trend change that went from antiretroviral treatment simplification regimen (56.1%) in the first part of the period analyzed to the therapeutic optimization (53.6%) in the second half. Furthermore, factors that were statistically significantly associated with antiretroviral treatment discontinuation were people with HIV ≥50 years (HR 1.60; 95%CI 1.25-2.04), post-discontinuation single-tablet regimen (HR 1.49; 95%CI 1.06-2.11) and antiretroviral drug classes. CONCLUSIONS: Over the 12 years there has been a change in the main cause of antiretroviral treatment discontinuation, currently therapeutic optimization being the main reason. Integrase inhibitors-based regimens and singletablet regimen strategies were less likely to be discontinued than others antiretroviral drug classes, allowing for better clinical management due to the efficacy profile, especially in people living with HIV ≥50 years with comorbidities.

Efficacy and Mechanism of Highly Active Umbilical Cord Mesenchymal Stem Cells in the Treatment of Osteoporosis in Rats.

Background: Osteoporosis increases bone brittleness and the risk of fracture. Umbilical cord mesenchymal stem cell (UCMSC) treatment is effective, but how to improve the biological activity and clinical efficacy of UCMSCs has not been determined. METHODS: A rat model of osteoporosis was induced with dexamethasone sodium phosphate. Highly active umbilical cord mesenchymal stem cells (HA-UCMSCs) and UCMSCs were isolated, cultured, identified, and infused intravenously once at a dose of 2.29 × 106 cells/kg. In the 4th week of treatment, bone mineral density (BMD) was evaluated via cross-micro-CT, tibial structure was observed via HE staining, osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was examined via alizarin red staining, and carboxy-terminal cross-linked telopeptide (CTX), nuclear factor-κß ligand (RANKL), procollagen type 1 N-terminal propeptide (PINP) and osteoprotegerin (OPG) levels were investigated via enzyme-linked immunosorbent assays (ELISAs). BMMSCs were treated with 10-6 mol/L dexamethasone and cocultured with HA-UCMSCs and UCMSCs in transwells. The osteogenic and adipogenic differentiation of BMMSCs was subsequently examined through directional induction culture. The protein expression levels of WNT, ß-catenin, RUNX2, IFN-γ and IL-17 in the bone tissue were measured via Western blotting. RESULTS: The BMD in the healthy group was higher than that in the model group. Both UCMSCs and HA-UCMSCs exhibited a fusiform morphology; swirling growth; high expression of CD73, CD90 and CD105; and low expression of CD34 and CD45 and could differentiate into adipocytes, osteoblasts and chondrocytes, while HA-UCMSCs were smaller in size; had a higher nuclear percentage; and higher differentiation efficiency. Compared with those in the model group, the BMD increased, the bone structure improved, the trabecular area, number, and perimeter increased, the osteogenic differentiation of BMMSCs increased, RANKL expression decreased, and PINP expression increased after UCMSC and HA-UCMSC treatment for 4 weeks. Furthermore, the BMD, trabecular area, number and perimeter, calcareous nodule counts, and OPG/RANKL ratio were higher in the HA-UCMSC treatment group than in the UCMSC treatment group. The osteogenic and adipogenic differentiation of dexamethasone-treated BMMSCs was enhanced after the coculture of UCMSCs and HA-UCMSCs, and the HA-UCMSC group exhibited better effects than the UCMSC coculture group. The protein expression of WNT, ß-catenin, and runx2 was upregulated, and IFN-γ and IL-17 expression was downregulated after UCMSC and HA-UCMSC treatment. CONCLUSION: HA-UCMSCs have a stronger therapeutic effect on osteoporosis compared with that of UCMSCs. These effects include an improved bone structure, increased BMD, an increased number and perimeter of trabeculae, and enhanced osteogenic differentiation of BMMSCs via activation of the WNT/ß-catenin pathway and inhibition of inflammation.

High-sensitivity C-reactive protein among people living with HIV on highly active antiretroviral therapy: a systemic review and meta-analysis.

The pathological consequences of inflammation persist in people living with the human immunodeficiency virus (PLWH), regardless of the positive outcomes of highly active antiretroviral therapy (HAART). The current systematic review and meta-analysis aims to understand and explore the levels of high-sensitivity C-reactive protein (hs-CRP) and other cardiovascular disease (CVD)-risk factors including lipid profiles among PLWH on HAART. Major electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve relevant global literature reporting on hs-CRP levels in PLWH on HAART. A total of twenty-two studies with an average participant age of 40 years were eligible for this systematic review and meta-analysis. Majority of the included studies were from Africa (n = 11), the United States (n = 6), and Europe (n = 5). Our systemic review showed that most studies reported increased levels of hs-CRP among PLWH on HAART when compared to controls (PLWH not on HAART or those without HIV), especially in studies from Africa. This was supported by a meta-analysis showing significantly elevated levels of hs-CRP in PLWH on HAART when compared to PLWH not on HAART (standardised mean difference [SMD] = 0.56; 95% CI = 0.10­1.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.76­1.63, z = 5.35; p < 0.001). Where lipid profiles, as a major predictor for CVD risk, were also impaired in PLWH on HAART when compared to PLWH not on HAART and HIV-negative participants. In conclusion, elevated levels of hs-CRP and lipid levels are prevalent in PLWH on HAART, this may increase the risk of CVD complications, especially for those people living in Africa. However, more evidence in larger population studies is required to confirm these outcomes and unveil any possible clinical implications of HAART-induced modulation of hs-CRP levels in PLWH.

Endothelial dysfunction and cardiovascular diseases in people living with HIV on specific highly active antiretroviral therapy regimen: A systematic review of clinical studies.

Despite the improved efficacy of highly active antiretroviral therapy (HAART) in viral suppression, emerging evidence indicates an increased burden of noncommunicable diseases in people living with HIV (PLWH). Immune activation and persistently elevated levels of inflammation have been associated with endothelial dysfunction in PLWH, likely contributing to the development of cardiovascular diseases (CVDs). Here, electronic search databases including PubMed, Google Scholar, Cochrane Library, and Science Direct were used to retrieve scientific evidence reporting on any association between markers of endothelial function and CVD-related outcomes in PLWH on HAART. Extracted data was subjected to quality assessment using the Downs and Black checklist. Most (60 %) of the results indicated the presence of endothelial dysfunction in PLWH on HAART, and this was mainly through reduced flow mediated dilation and elevated serum makers of adhesion molecules like ICAM-1, VCAM-1, and P-selectin. The summarized evidence indicates an association between persistently elevated markers of endothelial dysfunction and a pro-inflammatory state in PLWH on HAART. Only a few studies reported on improved endothelial function markers in PLWH on HAART, while limited evidence is available to prove that endothelial dysfunction is associated with CVD-risk, which could be attributed to therapeutic effects of HAART. Limited studies with relatively high quality of evidence were included in this systematic review. In conclusion, results from this review lay an important foundation for future research, even a meta-analysis, that will improve the understanding of the contributing factors to the burden of CVDs in PLWH on HAART.

Analysis of antiretroviral therapy interruption in people living with HIV during the 2010-2021 period.

INTRODUCTION: In the context of the advancement of antiretroviral therapy and as the characteristics of people living with HIV progress toward an ageing population, understanding the causes of treatment interruption becomes crucial. The aim of the study was to determine the change in reasons for antiretroviral treatment discontinuation for 12 years. Secondarily, compare annual antiretroviral regimen discontinuation rate and factors associated. METHODS: We conducted an analysis using data from people living with HIV who were receiving antiretroviral therapy and discontinued it for any reason. The study included people with HIV infection who visited an outpatient hospital pharmacy clinic from January 2010 to December 2021. Two periods were differentiated for the analysis: 2010-2015 and 2016-2021. The reasons for antiretroviral treatment discontinuation followed classification described by Swiss cohort. In the context of this study, it is pertinent to note that the term "discontinuation" is employed synonymously with "interruption". The term "discontinuation" will be consistently used in this article to refer to the act of switching or stopping antiretroviral treatment. To examine factors associated with antiretroviral therapy discontinuation, we utilised Kaplan-Meier methods and Cox proportional models. RESULTS: We included 789 people living with HIV, predominantly male (81.5%). The main reason for discontinuation was clinical decision (50.2%) followed by adverse effects (37.9%). Focusing on clinical decision, we observed a trend change that went from antiretroviral treatment simplification regimen (56.1%) in the first part of the period analysed to the therapeutic optimisation (53.6%) in the second half. Furthermore, factors that were statistically significantly associated with antiretroviral treatment discontinuation were people with HIV≥50 years (HR 1.60; 95%CI 1.25-2.04), post-discontinuation single-tablet regimen (HR 1.49; 95%CI 1.06-2.11) and antiretroviral drug classes. CONCLUSION: Over the 12 years, there has been a change in the main cause of antiretroviral treatment discontinuation, currently therapeutic optimisation being the main reason. Integrase inhibitors-based regimens and single-tablet regimen strategies were less likely to be discontinued than others antiretroviral drug classes, allowing for better clinical management due to the efficacy profile, especially in people living with HIV≥50 years with comorbidities.

Benefits of aHSCT over alemtuzumab in patients with multiple sclerosis besides disability and relapses: Sustained improvement in cognition and quality of life.

BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) exhibits promising results for multiple sclerosis (MS) in the short term. We investigated the long-term outcome differences in disease progression and cognitive impairment after aHSCT and alemtuzumab treatment. METHODS: 20 patients receiving aHSCT and 21 patients treated with alemtuzumab between 2007 and 2020 were included in this monocentric observational cohort study. The primary objective was to compare the outcome of both groups with regards to achieving No Evidence of Disease Activity (NEDA-3), defined by the absence of relapses, EDSS progression, and MRI activity. Secondary endpoints in the study included the assessment of neurocognitive functioning, quality of life (QoL), Multiple Sclerosis Functional Composite (MSFC), and EDSS improvement. RESULTS: Baseline characteristics between both groups were comparable, except for a longer disease duration in the alemtuzumab group of 11.3 years compared to 5.4 years in aHSCT-treated patients (p = 0.002) and a longer mean follow-up time in the aHSCT cohort of 9.0 (range 2.8-15.7) years compared to 5.9 years (range 0.9-9.2) in alemtuzumab patients. NEDA-3 was more frequently observed in the aHSCT group with 75.0 % and 55.0 % at five and 10 years, respectively, than in the alemtuzumab group with only 40.0 % at five years (p = 0.012). Relapse free survival was higher in the aHSCT group (p < 0.001). None of the aHSCT-treated patients showed new T2-lesions six months after therapy initiation until the end of the observational period in contrast to 35.0 % of the alemtuzumab-treated patients showing new T2-lesions (95 %CI 14.2-98.9, p = 0.002). aHSCT-treated patients showed significantly improved cognitive performance in five out of 12 cognitive tests whereas alemtuzumab treated patients deteriorated in four out of 12 tests. Quality of life remained on a constant level for up to 10 years in patients receiving aHSCT with improved scores for the subscale fatigue (p = 0.013). CONCLUSION: aHSCT seems to be superior to alemtuzumab in maintaining long-term NEDA-3 status, improving cognition and stabilizing quality of life for up to 10 years.

Weight loss and mortality in people living with HIV: a systematic review and meta-analysis.

BACKGROUND: In the first reported cases of human immunodeficiency virus (HIV) infection, people living with HIV (PLHIV) suffered weight loss, which was an independent predictor of mortality. Highly active antiretroviral therapy (HAART) has changed this scenario for ideal weight, overweight, and even obesity. However, some PLHIV, even on HAART, continue to lose weight. Thus, the guiding question of the study was: do PLHIV hospitalized using HAART with weight loss have higher mortality than hospitalized PLHIV using HAART without weight loss? METHOD: A systematic review and meta-analysis of prospective cohort studies published in English, Spanish, or Portuguese, searched in the MedLine, Embase, and LILACS databases from March 2020, until October 2023, reported by MOOSE. We analyzed the methodological quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Tool for Cohort Studies; used the risk ratio (RR) to calculate the probability of hospitalized PLWH who lost weight dying, applied the random effect model and created the funnel plot. We used the inverse variance test estimated by the Mantel-Haenszel method, considering a 95% confidence interval (CI), heterogeneity (I2), total effect size (Z), and significance value of p < 0.05. We performed a sensitivity analysis with meta-regression and meta-analyses on subgroups to diagnose influence and outliers. The quality of evidence and strength of recommendation were analyzed using the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE). RESULTS: We included 10 of the 711 studies identified, totaling 1,637 PLHIV. The studies were from South Africa (1), Canada (1), China (1), Brazil (1), Cameroon (1), Ethiopia (1), Thailand (1), Colombia (1), and Tanzania (2), from 1996 to 2017. The average age of the participants was 33.1 years old, and the male was predominant. The leading causes of hospital admission were related to co-infections, and the average hospitalization time was 20.5 days. The prevalence of death in hospitalized PLHIV using HAART who lost weight was 57.5%, with a 1.5 higher risk of dying (RR: 1.50, 95% CI: 1.03, 2.19, p = 0.04) than hospitalized PLHIV who did not lose weight. CONCLUSION: We concluded, with a very low confidence level, that that weight loss significantly increased the risk of death in hospitalized PLWH using HAART. TRIAL REGISTRATION AND FUNDING: PROSPERO International Prospective Register of Systematic Reviews CRD42020191246 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191246 .