scholarly journals HIV Antivirals Affect Endothelial Activation and Endothelial-Platelet Crosstalk

2020 ◽  
Vol 127 (11) ◽  
pp. 1365-1380
Author(s):  
Akif A. Khawaja ◽  
Kirk A. Taylor ◽  
Andrew O. Lovell ◽  
Mark Nelson ◽  
Brian Gazzard ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Antiretroviral Therapy ◽  
Endothelial Function ◽  
Platelet Activation ◽  
Tenofovir Disoproxil Fumarate ◽  
People Living With Hiv ◽  
Human Umbilical Cord ◽  
Increased Risk ◽  
Tenofovir Alafenamide ◽  
Living With Hiv

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.

scholarly journals Platelet activation in adult HIV-infected patients on antiretroviral therapy: a systematic review and meta-analysis

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Bongani B. Nkambule ◽  
Vuyolwethu Mxinwa ◽  
Zibusiso Mkandla ◽  
Tinashe Mutize ◽  
Kabelo Mokgalaboni ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Platelet Activation ◽  
Platelet Reactivity ◽  
Meta Analysis ◽  
Current Evidence ◽  
Secondary Outcome ◽  
Analysis Model ◽  
Increased Risk ◽  
Treatment Naïve ◽  
Living With Hiv

Abstract Background Antiretroviral therapy (ART) alters platelet reactivity, and as a consequence, patients living with HIV may be at an increased risk of cardiovascular disease (CVD). The current evidence on platelet activation levels in patients with HIV remains inconclusive. We therefore aimed to systematically synthesise evidence on the association of platelet activation in HIV-infected patients on successful treatment. Methods Electronic databases were searched from inception until November 2019. Studies were included if the primary or secondary outcome of the study was to assess platelet activation in HIV-infected patients on ART. The primary outcome of this review included the levels of platelet activation. The pooled effect estimates were calculated using a random-effects meta-analysis model. Results We identified 30 studies comprising of 2325 participants. The pooled estimates showed elevated levels of platelet activation in treatment-naïve HIV-infected patients compared to uninfected controls (Hedges’ g 2.00 [95%CI 1.05, 2.94]; z = 4.12, p < 0.0001). These remained elevated despite successful ART (Hedges’ g 2.05 [95%CI 0.58, 3.52]; z = 2.71, p = 0.0067). Conclusion The levels of platelet activation are elevated in treatment-naïve HIV-infected patients, and these persist during successful ART. Further studies should assess the clinical relevance of monitoring the levels of platelet activation in HIV-infected patients on ART.

Nursing Considerations for Patients With HIV in Critical Care Settings

2020 ◽  
Vol 31 (3) ◽  
pp. 308-317
Author(s):  
Lucy Graham ◽  
Mary Beth Flynn Makic
Keyword(s):  
Critical Care ◽  
Antiretroviral Therapy ◽  
People Living With Hiv ◽  
Secondary Complications ◽  
Qt Intervals ◽  
Appropriate Treatment ◽  
Increased Risk ◽  
History Of ◽  
Living With Hiv

Infection with HIV is a chronic condition that requires daily medication to suppress viral replication. With appropriate treatment, people living with HIV have a life expectancy approaching that of the general population. However, they are at increased risk for comorbidities including cardiovascular disease, renal disease, type 2 diabetes, neurologic conditions, and cancers, often with worse outcomes than in patients without HIV. When they are admitted to critical care settings, care considerations, particularly regarding antiretroviral therapy, must be addressed. Antiretroviral therapy is critical for successful management of HIV infection and should be continued when possible during intensive care unit stays. However, many antiretroviral regimens result in drug-drug interactions, adverse drug-related events, and secondary complications such as insulin resistance and prolonged QT intervals. Critical care nurses have unique opportunities to provide safe, unbiased, and compassionate care that promotes health for a population of people who have a history of being stigmatized.

scholarly journals Incidence and severity of drug interactions before and after switching antiretroviral therapy to bictegravir/emtricitabine/tenofovir alafenamide in treatment-experienced patients

2020 ◽  
Author(s):  
Jason J Schafer ◽  
Neha S Pandit ◽  
Agnes Cha ◽  
Emily Huesgen ◽  
Melissa Badowski ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Drug Interactions ◽  
Potential Interaction ◽  
People Living With Hiv ◽  
Interaction Database ◽  
Before And After ◽  
Tenofovir Alafenamide ◽  
The University ◽  
Living With Hiv ◽  
Paired T Test

Abstract Background Switching antiretroviral therapy (ART) in people living with HIV (PLWH) can influence their risk for drug-drug interactions (DDIs). The purpose of this study was to assess changes in the incidence and severity of DDIs among PLWH who switched their ART to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Methods This was a multicenter retrospective cohort study of PLWH on ART and at least one concomitant medication (CM) who switched to BIC/FTC/TAF between 3/2018 and 6/2019. Using the University of Liverpool’s HIV Drug Interaction Database, two DDI analyses were performed for each patient. The first assessed patients’ pre-switch ART regimens with their CM list. The second assessed the same CM list with BIC/FTC/TAF. Each ART-CM combination was given a score of zero (no or potential weak interaction), one (potential interaction), or two (contraindicated interaction). A paired t-test analyzed changes in total DDI scores following ART switches and linear regression examined factors contributing to DDI score reductions. Results Among 411 patients, 236 (57%) had at least one DDI present at baseline. On average, baseline DDI scores were 1.4 (SD 1.8) and decreased by 1-point (95% CI -1.1,-0.8) after patients switched to BIC/FTC/TAF (p &lt; 0.0001). After adjusting for demographics, baseline ART and CM categories, switching to BIC/FTC/TAF led to significant DDI score reductions in patients receiving CMs for cardiovascular disease, neurologic/psychiatric disorders, chronic pain, inflammation, gastrointestinal/urologic conditions and conditions requiring hormonal therapy. Conclusion Treatment-experienced PLWH eligible to switch their ART, may experience significant declines in their number and severity of DDIs if switched to BIC/FTC/TAF.

scholarly journals Influence of the duration of antiretroviral use on insulin resistance among people living with HIV with lipodystrophy

2018 ◽  
Vol 51 (4) ◽  
pp. 265-270
Author(s):  
Thiago Rodrigues Faria Vitorazzi ◽  
Taila Santos de Freitas ◽  
Loiane Sartori Oliveira ◽  
Anderson Marliere Navarro
Keyword(s):  
Insulin Resistance ◽  
Antiretroviral Therapy ◽  
Serum Insulin ◽  
Hiv Positive ◽  
People Living With Hiv ◽  
Lipodystrophy Syndrome ◽  
Special Unit ◽  
Increased Risk ◽  
Group 2 ◽  
Living With Hiv

Objective: The present study evaluated the influence of the duration of antiretroviral therapy on insulin resistance among people living with HIV with lipodystrophic syndrome. Methods: The study assessed 36 subjects of both sexes between 22 and 60 years old split into three groups: 1) HIV-positive using antiretroviral with lipodystrophy syndrome (HIV+LIPO+); 2) HIV-positive using antiretroviral therapy with no lipodystrophy syndrome (HIV+LIPO-); and 3) HIV-negative and healthy (Control). The data were collected at the Special Unit for the Treatment of Infectious Diseases (Unidade Especial de Tratamento para Doenças Infecciosas - UETDI) of the Dyslipidemia Outpatient Clinic (Ambulatório de Dislipidemia - ADIS) of the General Hospital of the Medical School of Ribeirão Preto (HC-FMRP). The biochemical assessment used laboratory kits when the results were not available in the volunteer's records. Results: Higher HOMA-IR values were observed for the group 1: HIV+LIPO+ (1,61 ± 1,17 ) compared to group 2: HIV+LIPO- (0,79 ± 0,87) and group 3: Control (0,46 ± 0,72 ) and such values were positively correlated with the time of antiretroviral medication use (r=0,41). Conclusions: The time of infection by HIV and the use of antiretrovirals impact the glucose metabolism with changes in serum insulin levels and consequent insulin resistance and increased risk for the development of diabetes and diseases related to carbohydrate metabolism.

scholarly journals Prevalence, beliefs and impact of drug-drug interactions between antiretroviral therapy and illicit drugs among people living with HIV in Spain

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260334
Author(s):  
Vanessa Castro-Granell ◽  
Noé Garin ◽  
Ángeles Jaén ◽  
Santiago Cenoz ◽  
María José Galindo ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Drug Use ◽  
Illicit Drugs ◽  
Significant Proportion ◽  
People Living With Hiv ◽  
Close Monitoring ◽  
Cross Sectional Survey ◽  
Increased Risk ◽  
Living With Hiv ◽  
The Impact

Drug use implies important challenges related to HIV management, particularly due to an increased risk of potential interactions between antiretroviral therapy (ART) and illicit drugs (pDDIs). This study analyses the prevalence and severity of pDDIs among people living with HIV (PLHIV). It also explores their awareness of pDDIs and their beliefs about the toxicity that they may cause, as well as the impact of pDDIs on selected health variables. We conducted an on-line cross-sectional survey across 33 Spanish hospitals and NGOs to collect demographics and clinical data. pDDIs were checked against the Interaction Checker developed by Liverpool University. The sample of the present study was composed of 694 PLHIV who used illicit drugs. They represented 49.5% of the 1,401 PLHIV that participated in the survey. After excluding 38 participants due to lack of information on their ART or illicit drug use, 335 (51.1%) participants consuming drugs presented with some potentially significant pDDIs between their ART and illicit drugs, with a mean of 2.1±1.7 (1–10) pDDIs per patient. The drugs most frequently involved in pDDIs were cocaine, cannabis, MDMA and nitrates ("poppers"). The prevalence of pDDIs across ART regimens was: protease inhibitors (41.7%); integrase inhibitor-boosted regimens (32.1%), and non-nucleoside reverse transcriptase inhibitors (26.3%). An awareness of pDDIs and beliefs about their potential toxicity correlated positively with intentional non-adherence (p<0.0001). Participants with pDDIs exhibited a higher prevalence of intentional non-adherence (2.19±1.04 vs. 1.93±0.94; p = 0.001). The presence of pDDIs was not associated with poorer results in the clinical variables analysed. A significant proportion of PLHIV who use drugs experience pDDIs, thereby requiring close monitoring. pDDIs should be considered in the clinical management of HIV patients. Adequate information about pDDIs and indicators about how to manage ART when PLHIV use drugs could improve ART non-adherence.

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 ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Antiretroviral Therapy ◽  
Tenofovir Disoproxil Fumarate ◽  
Categorical Variables ◽  
People Living With Hiv ◽  
Median Regression ◽  
Multivariate Median ◽  
General Populations ◽  
Living With Hiv

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.

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