scholarly journals Tenofovir Disoproxil Fumarate Is Associated with a Set-Point Variation in the Calcium-Parathyroid Hormone-Vitamin D Axis: Results from a German Cohort

2018 ◽  
Vol 2018 ◽  
pp. 1-6
Author(s):  
Sebastian Noe ◽  
Silke Heldwein ◽  
Carmen Wiese ◽  
Rita Pascucci ◽  
Ariane von Krosigk ◽  
...  

Background. Higher levels of parathyroid hormone have been associated with the use of tenofovir disoproxil fumarate (TDF) in people with and without HIV infection. Yet, alterations in calcium levels have never been elucidated in detail. Objective. To compare the association of parathyroid hormone with serum calcium levels and other markers of calcium and bone metabolism in people living with HIV on TDF- and non-TDF-containing antiretroviral therapy. Patients and Methods. A retrospective single center cohort study in Munich, Germany. Median and interquartile ranges and absolute and relative frequencies were used to describe continuous and categorical variables, respectively. The Mann–Whitney U test and chi2-test were used for comparisons. Multivariate median regression was performed in a stepwise backward approach. Results. 1,002 patients were included (786 (78.4%) male; median age 48 (40–55) years). 564 patients (56.3%) had a TDF-containing ART regimen. PTH concentrations were 46.9 (33.0–64.7) pg/mL and 35.2 (26.4–55.4) pg/mL (P=0.001), 43.3 (30.8–59.8) pg/mL and 31.8 (22.3–49.6) pg/mL (P<0.001), 46.1 (29.5–65.4) pg/mL and 33.4 (22.6–50.1) pg/mL (P<0.001), and 37.8 (25.3–57.9) pg/mL and 33.8 (20.1–45.3) pg/mL (P=0.012) within the first, second, third, and fourth quartile of corrected calcium levels for patients with and without TDF-containing ART, respectively. In multivariate median regression, PTH concentration was significantly associated with Cacorr. (−32.2 (−49.8 to −14.8); P<0.001), female sex (5.2 (1.2–9.2); P=0.010), 25(OH)D (−0.4 (−0.5 to −0.3); P<0.001), and TDF-use (9.2 (6.0–12.5); P<0.001). Discussion. Higher levels of PTH seem to be needed to maintain normal calcium levels in PLWH on TDF-containing ART compared to non-TDF-containing ART. Optimal concentrations for 25-hydroxy vitamin D and calcium might therefore be different in people using TDF than expected from general populations but also people living with HIV with non-TDF-containing antiretroviral therapy. This might require different supplementation strategies but warrants further investigation.

2020 ◽  
Vol 127 (11) ◽  
pp. 1365-1380
Author(s):  
Akif A. Khawaja ◽  
Kirk A. Taylor ◽  
Andrew O. Lovell ◽  
Mark Nelson ◽  
Brian Gazzard ◽  
...  

Rationale: People living with HIV on effective antiretroviral therapy are at increased risk of cardiovascular complications, possibly due to off-target drug effects. Some studies have associated antiretroviral therapy with increased risk of myocardial infarction and endothelial dysfunction, but a link between endothelial function and antiretrovirals has not been established. Objective: To determine the effects of antiretrovirals in common clinical use upon in vitro endothelial function to better understand cardiovascular risk in people living with HIV. Methods and Results: Human umbilical cord vein endothelial cells or human coronary artery endothelial cells were pretreated with the antiretrovirals abacavir sulphate (ABC), tenofovir disoproxil fumarate, or tenofovir alafenamide. Expression of adhesion molecules, ectonucleotidases (CD39 and CD73), tissue factor (TF), endothelial-derived microparticle (EMP) numbers and phenotype, and platelet activation were evaluated by flow cytometry. TF and ectonucleotidase activities were measured using colourimetric plate-based assays. ABC-treated endothelial cells had higher levels of ICAM (intercellular adhesion molecule)-1 and TF expression following TNF (tumor necrosis factor)-α stimulation. In contrast, tenofovir disoproxil fumarate and tenofovir alafenamide treatment gave rise to greater populations of CD39 + CD73 + cells. These cell surface differences were also observed within EMP repertoires. ABC-treated cells and EMP had greater TF activity, while tenofovir disoproxil fumarate- and tenofovir alafenamide-treated cells and EMP displayed higher ectonucleotidase activity. Finally, EMP isolated from ABC-treated cells enhanced collagen-evoked platelet integrin activation and α-granule release. Conclusions: We report differential effects of antiretrovirals used in the treatment of HIV upon endothelial function. ABC treatment led to an inflammatory, prothrombotic endothelial phenotype that promoted platelet activation. In contrast, tenofovir disoproxil fumarate and tenofovir alafenamide conferred potentially cardioprotective properties associated with ectonucleotidase activity. These observations establish a link between antiretrovirals and specific functional effects that provide insight into cardiovascular disease in people living with HIV.


2020 ◽  
Vol 18 (6) ◽  
pp. 388-395
Author(s):  
Daniel Vargas-Pacherrez ◽  
Helma P. Cotrim ◽  
Leonardo Pires ◽  
Vitor Cunha ◽  
Vitor Coelho ◽  
...  

Introduction: The global prevalence of metabolic syndrome (MS) among people living with HIV/AIDS varies from 20% to 33%. Objective: to estimate the prevalence of metabolic syndrome and associated factors in a group of HIV-infected patients on antiretroviral therapy. Methods: This is a cross-sectional study with HIV-infected patients from a reference center in Bahia, Brazil. We evaluated clinical, socio-demographic and anthropometric data. MS was defined according to the guidelines of International Diabetes Federation. Results: We evaluated 152 patients with mean age of 47.3±11.6 years, 59.2% male. The main comorbidities detected were diabetes (3.3%) hypertriglyceridemia (9.3%) and metabolic syndrome (MS,38.2%). Patients with MS were predominantly women (55.2% vs 31.9%; p=0.005), older [52.1 (10.4) vs 44.3 (11.3); p<0.001], and had overweight (74.1% vs 23.4%; p<0.001). After multivariate analysis MS remained associated with age (OR = 1.076; 95% CI: 1.030 – 1.125), female sex (OR = 2.452; 95% CI: 1.114 – 5.374) and family history of hypertension (OR = 3.678; 95% CI: 1.431 – 9.395). Conclusion: Almost half of the HIV-infected patients in Bahia presents with MS which seems to be driven by classical risk factors.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sovannary Tuot ◽  
Alvin Kuo Jing Teo ◽  
Kiesha Prem ◽  
Pheak Chhoun ◽  
Chamroen Pall ◽  
...  

Abstract Background Multi-month dispensing (MMD) is the mainstay mechanism for clinically stable people living with HIV in Cambodia to refill antiretroviral therapy (ART) every 3-6 months. However, less frequent ART dispensing through the community-based ART delivery (CAD) model could further reduce the clients’ and health facilities’ burden. While community-based services have been recognized as an integral component of HIV response in Cambodia, their role and effectiveness in ART delivery have yet to be systematically assessed. This study aims to evaluate the CAD model’s effectiveness on the continuum of care and treatment outcomes for stable people living with HIV in Cambodia. Methods We will conduct this quasi-experimental study in 20 ART clinics across the capital city and nine provinces between May 2021 and April 2023. Study sites were purposively selected based on the availability of implementing partners, the number of people living with HIV each clinic serves, and the accessibility of the clinics. In the intervention arm, approximately 2000 stable people living with HIV will receive ART and services from the CAD model. Another 2000 stable people living with HIV in the control arm will receive MMD—a standard care model for stable people living with HIV. The primary outcomes will be retention in care, viral load suppression, and adherence to ART. The secondary endpoints will include health providers’ work burden, the model’s cost-effectiveness, quality of life, mental health, social support, stigma, and discrimination. We will compare the outcome indicators within each arm at baseline, midline, and endline using descriptive and inferential statistics. We will evaluate the differences between the intervention and control arms using the difference-in-differences method. We will perform economic evaluations to determine if the intervention is cost-effective. Discussion This study will build the evidence base for future implementation and scale-up of CAD model in Cambodia and other similar settings. Furthermore, it will strengthen engagements with community stakeholders and further improve community mobilization, a vital pillar of the Cambodian HIV response. Trial registration ClinicalTrials.gov, NCT04766710. Registered 23 February 2021, Version 1.


2021 ◽  
Vol 10 (11) ◽  
pp. 2300
Author(s):  
Han-Chang Ku ◽  
Yi-Tseng Tsai ◽  
Sriyani-Padmalatha Konara-Mudiyanselage ◽  
Yi-Lin Wu ◽  
Tsung Yu ◽  
...  

The incidence of herpes zoster (HZ) in patients infected with HIV is higher than that of the general population. However, the incidence of HZ in HIV patients receiving antiretroviral therapy (ART) remains unclear. This meta-analysis aimed to estimate the pooled incidence rate and risk factors for HZ in the post-ART era. We identified studies assessing the incidence of HZ in the post-ART era between 1 January 2000 and 28 February 2021, from four databases. Pooled risk ratios were calculated from 11 articles using a random-effects model. The heterogeneity of the included trials was evaluated by visually inspecting funnel plots, performing random-effects meta-regression and using I2 statistics. Of the 2111 studies screened, we identified 11 studies that were eligible for final inclusion in the systematic review and 8 studies that were eligible for a meta-analysis. The pooled incidence of HZ in the post-ART era (after the introduction of ART in 1997) was 2.30 (95% confidence interval (CI): 1.56–3.05) per 100 person years (PYs). The risks of incidence of HZ among people living with HIV included male sex (AOR: 4.35 (95% CI: 054–2.41)), men who have sex with men (AOR: 1.21 (95% CI: −0.76–1.13)), CD4 count < 200 cells/μL (AOR: 11.59 (95% CI: 0.53–4.38)) and not receiving ART (AOR: 2.89 (95% CI: −0.44–2.56)). The incidence of HZ is substantially lower among HIV infected patients receiving ART than those not receiving ART. Initiating ART immediately after diagnosis to treat all HIV-positive individuals is crucial to minimize the disease burden of HZ.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S506-S506
Author(s):  
Folusakin Ayoade ◽  
Dushyantha Jayaweera

Abstract Background The risk of ischemic stroke (IS) is known to be higher in people living with HIV (PLWH) than uninfected controls. However, information about the demographics and risk factors for hemorrhagic stroke (HS) in PLWH is scant. Specifically, very little is known about the differences in the stroke risk factors between HS and IS in PLWH. The goal of this study was to determine the demographics and risk factor differences between HS and IS in PLWH. Methods We retrospectively analyzed the demographic and clinical data of PLWH in OneFlorida (1FL) Clinical Research Consortium from October 2015 to December 2018. 1FL is a large statewide clinical research network and database which contains health information of over 15 million patients, 1240 clinical practices, and 22 hospitals. We compared HS and IS based on documented ICD 9 and 10 diagnostic codes and extracted information about sociodemographic data, traditional stroke risk factors, Charlson comorbidity scores, habits, HIV factors, diagnostic modalities and medications. Statistical significance was determined using 2-sample T-test for continuous variables and adjusted Pearson chi square for categorical variables. Odds ratio (OR) and 95% confidence intervals (CI) between groups were compared. Results Overall, from 1FL sample of 13986 people living with HIV, 574 subjects had strokes during the study period. The rate of any stroke was 18.2/1000 person-years (PYRS). The rate of IS was 10.8/1000 PYRS while the rate of HS was 3.7/1000 PYRS, corresponding to 25.4% HS of all strokes in the study. Table 1 summarizes the pertinent demographic and risk factors for HS and IS in PLWH in the study. Table 1: Summary of pertinent demographic and risk factors for hemorrhagic and ischemic strokes in people living with HIV from One Florida database Conclusion In this large Floridian health database, demographics and risk factor profile differs between HS and IS in PLWH. Younger age group is associated with HS than IS. However, hypertension, hyperlipidemia and coronary artery disease are more likely to contribute to IS than HS in PLWH. Further research is needed to better understand the interplay between known and yet unidentified risk factors that may be contributing to HS and IS in PLWH. Disclosures All Authors: No reported disclosures


The Analyst ◽  
2021 ◽  
Author(s):  
Andrew T. Bender ◽  
Benjamin P. Sullivan ◽  
Jane Zhang ◽  
David C Juergens ◽  
Lorraine Lillis ◽  
...  

The number of people living with HIV continues to increase with the current total near 38 million, of which about 26 million are receiving antiretroviral therapy (ART). These treatment regimens...


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 909
Author(s):  
Laura Cheney ◽  
John M. Barbaro ◽  
Joan W. Berman

Antiretroviral drugs have dramatically improved the morbidity and mortality of people living with HIV (PLWH). While current antiretroviral therapy (ART) regimens are generally well-tolerated, risks for side effects and toxicity remain as PLWH must take life-long medications. Antiretroviral drugs impact autophagy, an intracellular proteolytic process that eliminates debris and foreign material, provides nutrients for metabolism, and performs quality control to maintain cell homeostasis. Toxicity and adverse events associated with antiretrovirals may be due, in part, to their impacts on autophagy. A more complete understanding of the effects on autophagy is essential for developing antiretroviral drugs with decreased off target effects, meaning those unrelated to viral suppression, to minimize toxicity for PLWH. This review summarizes the findings and highlights the gaps in our knowledge of the impacts of antiretroviral drugs on autophagy.


BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e049824
Author(s):  
Andreas D Haas ◽  
Cordelia Kunzekwenyika ◽  
Stefanie Hossmann ◽  
Josphat Manzero ◽  
Janneke van Dijk ◽  
...  

ObjectivesTo examine the proportion of people living with HIV who screen positive for common mental disorders (CMD) and the associations between CMD and self-reported adherence to antiretroviral therapy (ART).SettingSixteen government-funded health facilities in the rural Bikita district of Zimbabwe.DesignCross-sectional study.ParticipantsHIV-positive non-pregnant adults, aged 18 years or older, who lived in Bikita district and had received ART for at least 6 months.Outcome measuresThe primary outcome was the proportion of participants screening positive for CMD defined as a Shona Symptoms Questionnaire score of 9 or greater. Secondary outcomes were the proportion of participants reporting suicidal ideation, perceptual symptoms and suboptimal ART adherence and adjusted prevalence ratios (aPR) for factors associated with CMD, suicidal ideation, perceptual symptoms and suboptimal ART adherence.ResultsOut of 3480 adults, 18.8% (95% CI 14.8% to 23.7%) screened positive for CMD, 2.7% (95% CI 1.5% to 4.7%) reported suicidal ideations, and 1.5% (95% CI 0.9% to 2.6%) reported perceptual symptoms. Positive CMD screens were more common in women (aPR 1.67, 95% CI 1.19 to 2.35) than in men and were more common in adults aged 40–49 years (aPR 1.47, 95% CI 1.16 to 1.85) or aged 50–59 years (aPR 1.51, 95% CI 1.05 to 2.17) than in those 60 years or older. Positive CMD screen was associated with suboptimal adherence (aPR 1.53; 95% CI 1.37 to 1.70).ConclusionsA substantial proportion of people living with HIV in rural Zimbabwe are affected by CMD. There is a need to integrate mental health services and HIV programmes in rural Zimbabwe.Trial registration numberNCT03704805.


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