NCT04301661

Cellular Pharmacology and Platelet Effects of Abacavir and Lamivudine Anabolites

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 25 (actual)
• Sponsor: University of Colorado, Denver · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

This study will evaluate the intracellular pharmacokinetics and platelet effects of abacavir (ABC), lamivudine (3TC), tenofovir alafenamide (TAF), and emtricitabine (FTC) in persons living with HIV that are receiving these medications as part of standard HIV care. Participants remaining on ABC/3TC- or TAF/FTC-containing therapy will be on study for 4 weeks, and will have two visits: a screening visit and one short PK visit consisting of a single blood draw at week 4. Participants switching from their ABC/3TC-containing therapy will be on study for 3 weeks, and will have nine visits: a screening visit and 8 short PK visits consisting of a single blood draw at Day 0, 1, 3, 7, 10, 14, 18, and 21.

Detailed description

Abacavir and lamivudine are recommended antiretroviral medications used in the treatment of human immunodeficiency virus (HIV) infection in the United States and globally. Both agents are nucleos(t)ide reverse transcriptase inhibitors (NRTIs), which exert their antiviral activity following entry into target cells and phosphorylation by intracellular kinases to their active anabolites, carbovir-triphosphate (CBV-TP) and lamivudine-triphosphate (3TC-TP). There is limited knowledge regarding the pharmacokinetic (PK) disposition of abacavir and lamivudine anabolites in red blood cells (RBCs), neutrophils, and platelets. Abacavir has also been linked with prothrombotic activity and an increased risk of cardiovascular events in patients on this therapy, central theories of which point towards interference with purinergic signaling due to its structural similarity to endogenous adenosine and guanosine. These findings have not been replicated with other NRTI medications, such as tenofovir. This pilot study will characterize the pharmacokinetics (PK) of these medications in different cell types of persons living with HIV (PLWH) on these therapies as part of clinical care, and will examine endogenous nucleotide levels and metabolic profiles through the use of metabolomics in platelets specifically to better understand what changes might be happening within this cell type with the use of these medications.

Conditions

• HIV-1-infection

Interventions

Type	Name	Description
OTHER	Blood collection	Blood will be collected from participants at defined time points during the study to measure drug levels and assess platelet activity.
DRUG	Abacavir/lamivudine	Participants who are already taking abacavir/lamivudine as part of standard HIV care will continue taking their therapy.
DRUG	Tenofovir alafenamide/emtricitabine	Participants who are already taking tenofovir alafenamide/emtricitabine as part of standard HIV care will continue taking their therapy.
DRUG	Switch	Participants who are planning to switch from abacavir/lamivudine as part of standard HIV care will change therapy to per the discretion of their HIV provider.

Timeline

• Start date: 2020-03-06
• Primary completion: 2021-12-17
• Completion: 2021-12-17
• First posted: 2020-03-10
• Last updated: 2023-01-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study