scholarly journals Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living with HIV: Lipid Changes and Statin Underutilization

2021 ◽  
Author(s):  
Laurence Brunet ◽  
Patrick Mallon ◽  
Jennifer S. Fusco ◽  
Michael B. Wohlfeiler ◽  
Girish Prajapati ◽  
...  
Keyword(s):  
Tenofovir Disoproxil Fumarate ◽  
People Living With Hiv ◽  
Tenofovir Alafenamide ◽  
Living With Hiv

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 Impact of switch from tenofovir disoproxil fumarate-based regimens to tenofovir alafenamide-based regimens on lipid profile, weight gain and cardiovascular risk score in people living with HIV

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Pierre-Emmanuel Plum ◽  
Nathalie Maes ◽  
Anne-Sophie Sauvage ◽  
Frédéric Frippiat ◽  
Christelle Meuris ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Viral Load ◽  
Weight Gain ◽  
Lipid Profile ◽  
Total Cholesterol ◽  
Tenofovir Disoproxil Fumarate ◽  
Negative Impact ◽  
People Living With Hiv ◽  
Tenofovir Alafenamide ◽  
Living With Hiv

Abstract Background As cardiovascular diseases represent the main cause of non-AIDS related death in people living with HIV (PLWH) with undetectable viral load, we evaluated lipid profile, weight gain and calculated cardiovascular risk change after switching from tenofovir disoproxil fumarate (TDF)-based regimens to tenofovir alafenamide (TAF)-based regimens. Methods For this retrospective study, we selected HIV-infected patients with suppressed viral load who fitted in one of the two groups below: First group (TDF/TDF): Patients treated continuously with TDF-based regimens. Second group (TDF/TAF): Patients treated with TDF-regimens during at least 6 months then switched to TAF-regimens while maintaining other drugs unchanged. Available data included date of birth, gender, ethnicity, lymphocyte T CD4+ count, weight, height, blood pressure, current/ex/non-smoker, diabetes mellitus, familial cardiovascular event, lipid profile, duration and nature of antiretroviral therapy. Lipid parameters, weight and calculated cardiovascular risk using 5-year reduced DAD score algorithm [Friis-Møller et al. in Eur J Cardiovasc Prev Rehabil 17:491–501, 2010] were analyzed in each groups. Results Switching from TDF to TAF resulted in a significant increase in triglycerides levels, total cholesterol and HDL cholesterol. LDL cholesterol and total cholesterol/HDL ratio did not show significant changes. Calculated cardiovascular risk increased after switch from TDF- to TAF-based therapy. Conclusions Together with favorable outcomes at the bone and kidney levels, potential negative impact of TAF on lipid profile should be included in the reflection to propose the most appropriate and tailored ARV treatment.

scholarly journals Dynamics of the Decay of Human Immunodeficiency Virus (HIV) RNA and Distribution of Bictegravir in the Genital Tract and Rectum in Antiretroviral-naive Adults Living With HIV–1 Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (Spanish HIV/AIDS Research Network, PreEC/RIS 58)

2020 ◽  
Author(s):  
Arkaitz Imaz ◽  
Juan M Tiraboschi ◽  
Jordi Niubó ◽  
Javier Martinez-Picado ◽  
Mackenzie L Cottrell ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Research Network ◽  
People Living With Hiv ◽  
Limit Of Quantification ◽  
Immunodeficiency Virus ◽  
Liquid Chromatography Tandem Mass ◽  
Half Maximal Effective Concentration ◽  
Tenofovir Alafenamide ◽  
Living With Hiv ◽  
Hiv 1

Abstract Background The pharmacokinetics of bictegravir (BIC) and its association with the decay of human immunodeficiency virus (HIV)–1 RNA in genital fluids and the rectum have not yet been addressed. Methods We conducted a prospective, multicenter study of antiretroviral-naive people living with HIV-1 and initiating BIC/emtricitabine (FTC)/tenofovir alafenamide (TAF). HIV-1 RNA was measured (limit of quantification, 40 copies/mL) in blood plasma (BP), seminal plasma (SP), rectal fluid (RF), and cervicovaginal fluid (CVF) at baseline; Days 3, 7, 14, and 28; and Weeks 12 and 24. Total and protein-unbound BIC concentrations at 24 hours postdose (C24h) were quantified in BP, SP, CVF and rectal tissue (RT) on Day 28 and Week 12 using a validated liquid chromatography-tandem mass spectrometry assay. Results The study population comprised 15 males and 8 females. In SP, RF, and CVF, the baseline HIV-1 RNA was >40 copies/mL in 12/15, 13/15, and 4/8 individuals, respectively, with medians of 3.54 (2.41–3.79), 4.19 (2.98–4.70), and 2.56 (1.61–3.56) log10 copies/mL, respectively. The initial decay slope was significantly lower in SP than in RF and BP. The time to undetectable HIV-1 RNA was significantly shorter in SP and RF than in BP. All women achieved undetectable HIV-1 RNA in CVF at Day 14. The median total BIC concentrations in SP, RT, and CVF were 65.5 (20.1–923) ng/mL, 74.1 (6.0–478.5) ng/g, and 61.6 (14.4–1760.2) ng/mL, respectively, representing 2.7%, 2.6%, and 2.8% of the BP concentration, respectively, while the protein-unbound fractions were 51.1%, 44.6%, and 42.6%, respectively. Conclusions BIC/FTC/TAF led to rapid decay of HIV-1 RNA in genital and rectal fluids. Protein-unbound BIC concentrations in SP, RT, and CVF highly exceeded the half-maximal effective concentration (EC50) value (1.1 ng/mL). Clinical Trials Registration EudraCT 2018-002310-12.

scholarly journals Improved Central Nervous System Symptoms in People with HIV without Objective Neuropsychiatric Complaints Switching from Efavirenz to Rilpivirine Containing cART

2019 ◽  
Vol 9 (8) ◽  
pp. 195 ◽  
Author(s):  
Vera ◽  
Bracchi ◽  
Alagaratnam ◽  
Lwanga ◽  
Fox ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tenofovir Disoproxil Fumarate ◽  
Patient Reported Outcome Measures ◽  
Patient Reported Outcome ◽  
People Living With Hiv ◽  
White Ethnicity ◽  
Patient Reported ◽  
Switching Therapy ◽  
Living With Hiv

Objective: Occult central nervous system (CNS) symptoms not recognized by people living with HIV (PLWH) receiving efavirenz or their clinicians could occur and impact people’s quality of life. The aim of this study was to determine whether CNS parameters improve in PLWH when switching from efavirenz to rilpivirine. Methods: PLWH receiving tenofovir disoproxil fumarate, emtricitabine, efavirenz (Atripla™) with undetectable HIV RNA, and no CNS symptoms were switched cART to tenofovir disoproxil fumarate, emtricitabine, rilpivirine (Eviplera™). CNS parameters including sleep, anxiety, and depressive symptoms were evaluated using patient-reported outcome measures at baseline, 4, 12, and 24 weeks after switching therapy. A median CNS score was derived from the sum of CNS toxicities of all the grades collected in the study questionnaires. Cognitive function was assessed using a computerized test battery. Results: Of 41 participants, median age was 47 years, Interquartile range (IQR) 31, 92% were male and 80% were of white ethnicity. A significant reduction in total CNS score (10 to 7) was observed at 4 weeks (p = 0.028), but not thereafter. Significant improvements in sleep and anxiety were observed 4, 12 and 24 weeks after switching therapy (p < 0.05). No significant change in global cognitive scores was observed. Conclusions: Switching from efavirenz to rilpivirine based regimens in virologically suppressed PLWH without perceived CNS symptoms was well tolerated and slightly improved overall CNS symptoms.

Cerebrospinal fluid exposure to bictegravir/emtricitabine/tenofovir in HIV-1-infected patients with CNS impairment

2021 ◽  
Author(s):  
Thibaut Gelé ◽  
Antoine Chéret ◽  
Alicia Castro Gordon ◽  
Lionelle Nkam ◽  
Valérie Furlan ◽  
...  
Keyword(s):  
Real Life ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Hiv Cure ◽  
Crucial Component ◽  
Total Plasma Concentration ◽  
Tenofovir Alafenamide ◽  
Living With Hiv ◽  
Csf Concentration ◽  
Hiv 1

Abstract Objectives The penetration of antiretroviral drugs into deep compartments, such as the CNS, is a crucial component of strategies towards an HIV cure. This study aimed to determine CSF concentrations of bictegravir, emtricitabine and tenofovir in patients with HIV-related CNS impairment (HCI) enrolled in a real-life observational study. Methods Patients with HCI treated by optimized ART, including bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) for at least 1 month were enrolled. Plasma and CSF concentrations were measured by quality control-validated assays (LC-MS/MS). The inhibitory quotient (IQARV) was calculated as the ratio of unbound (bictegravir) or total (emtricitabine and tenofovir) concentration to half (or 90%) maximal inhibitory concentration for bictegravir (or emtricitabine and tenofovir). All numerical variables are expressed as median (range). Results Twenty-four patients (nine women) were enrolled. The age was 45 (26–68) years. Unbound bictegravir and total emtricitabine and tenofovir CSF concentrations were 4.4 (1.6–9.6), 84.4 (28.6–337.4) and 1.6 (0.7–4.3) ng/mL, respectively. The unbound bictegravir CSF fraction was 34% (15%–82%) versus 0.33% (0.11%–0.92%) in plasma. Three patients had an IQARV above unity for the three antiretrovirals. Factors positively associated with the CSF concentration (unbound for bictegravir) were age and total plasma concentration for the three antiretrovirals. Patients aged over 51 years had higher CSF concentrations (unbound for bictegravir). Conclusions We observed low CSF exposure to bictegravir, emtricitabine and tenofovir. These results suggest that BIC/FTC/TAF should be used with caution as first-line treatment for people living with HIV with HCI under 51 years of age.

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