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.

Impact of serious adverse drug reactions on the quality of life of patients on highly active antiretroviral therapy in Maiduguri, northeast Nigeria: a four-year retrospective study.

ABSTRACTSerious adverse drug reactions (sADRs) have a serious impact on the progress being made in providing antiretroviral therapy. The presence of HIV/AIDS and its complications associated with sADRs, has a negative effect on the quality of life (QoL) of people living with HIV/AIDS (PLWHA). This was a descriptive retrospective cohort study of 400 adult HIV patients in which the QoL of PLWHA with sADRs was compared to patients that did not experience ADR who had been on antiretroviral therapy (ART) was followed up for 48 months using the WHOQOL-HIV BREF to measure QoL. Out of 400 patients, 373 (93.25%) respondents completed the study with an overall mean age was 40.8 years (SD ± 8.64). One hundred and ninety-nine patients (53.4%) reported to have experiencing sADR. The response consistently showed significantly higher mean scores in the QoL of patients who had no ADRs in the psychological, social and environments state of health domains compared to those who had ADRs with mean scores (P = 0.000, 0.037 and 0.028), respectively. This study revealed significantly higher scores in patients who had no ADRs compared to those who had ADRs. Low QoL due to serious ADR may add additional burden to HIV disease and complications, and the related discrimination often faced by PLWHA. This study would help clinicians pay serious attention to identifying and promptly managing ADR.

Association between CD4 lymphocyte count and the incidence of comorbidities in Human immunodeficiency virus positive patients with virological suppression after antiretroviral treatment.

BACKGROUND: The incidence of comorbidities is higher in HIV-positive patients than in the general population due to factors, such as HIV-related chronic inflammation. There is no consensus on whether a low CD4 lymphocyte count after virological suppression at long-term follow-up increases the risk of comorbidities. This study evaluates the association between CD4 lymphocyte count and the incidence of comorbidities during the first 5 years of virological suppression after highly active antiretroviral treatment. METHODS: We conducted a cohort study of HIV-positive adults who achieved virological suppression in an HIV program between 2002 and 2016 in Colombia. A generalized equation estimation model was used to estimate the association between CD4 lymphocyte count and the incidence of comorbidities. RESULTS: A follow-up period of at least 1 year was completed in 921 HIV-positive patients with virological suppression. We found 71 comorbidities during a maximum of 5 years of follow-up; 41 (59%) were AIDS-defining comorbidities and 19 (46%) of them occurred during the first semester. Thirty cases of non-AIDS- defining comorbidities were diagnosed.We did not find any association between CD4 lymphocyte count and the incidence of comorbidities (OR 0.92, CI 95% 0.45 -1.91 for CD4 201-499 cells/µL vs CD4 ≤200 cells/µL, and OR 0.55, 95% CI 0.21-1.44 for CD4 ≥500 cells/µL vs CD4 ≤200 cells/µL). CONCLUSION: No association was found between CD4 lymphocyte count and the incidence of AIDS-defining or non-AIDS-defining comorbidities in patients with virological suppression. Further studies are needed to assess the risk of comorbidities in this population to design interventions aimed at improving their prognosis.

Making new drugs the hard way.

A new drug can have its origin in either pharma, biotech or academia. In general, discovery scientists working in pharma and biotech are advantaged over their academic counterparts and the relative advantages and disadvantages associated are discussed in depth. Against all odds, an increasing number of important drugs have had their origins in academia. This article reports three case studies from the Liotta Research Group (LRG), which explores the special circumstances that allowed these drug development campaigns to be successful. The first involves the antiretroviral agent, emtricitabine. In this case efficient synthetic methodology, developed in the LRG, coupled with some key university and commercial sector partnerships, enabled a group of academic collaborators to discover and develop a highly effective HIV reverse transcriptase inhibitor. The second case study involves the discovery and development of the breakthrough hepatitis C drug, sofosbuvir. Based on key input from Professors Schinazi and Liotta at Emory University, scientists at the Emory startup, Pharmasset, identified the nucleoside core of the drug that would become sofosbuvir. Subsequent analysis of its phosphorylation profile by Pharmasset scientists suggested that converting it to its corresponding monophosphate prodrug would circumvent a kinase block and enable it to be an effective hepatitis C polymerase inhibitor. The third case study describes the formation of DRIVE (Drug Innovation Ventures at Emory)/EIDD (Emory Institute for Drug Development), which were created to circumvent unintended impediments for carrying out academic drug discovery and development. Although DRIVE/EIDD is a wholly-owned, not-for-profit subsidiary of Emory University, it contains many attributes that enables it to operate much more nimbly than a typical academic laboratory. With an experienced drug development team and no shareholders to distract them, DRIVE/EIDD was able to focus its attention of the development of drugs to address viral diseases of global concern. In particular, their strategy to identify and develop an antiviral agent active against multiple single-stranded RNA viruses led to molnupiravir, a broadly active, oral drug that received Emergency Use Authorization for the treatment of SARS-CoV-2 infections (i.e., COVID-19).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.