Cellular Pharmacology and Platelet Effects of Abacavir and Lamivudine Anabolites

NCT ID: NCT04301661

Last Updated: 2023-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

25 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-03-06

Study Completion Date

2021-12-17

Brief Summary

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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

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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

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HIV-1-infection

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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ABC/3TC Cohort

Persons on abacavir/lamivudine-containing therapy as part of their standard HIV care will continue to take their prescribed HIV medications.

Participants will be on study for 4 weeks, and will participate in directly observed therapy for the 4 weeks leading up to a single blood draw.

Blood collection

Intervention Type OTHER

Blood will be collected from participants at defined time points during the study to measure drug levels and assess platelet activity.

Abacavir/lamivudine

Intervention Type DRUG

Participants who are already taking abacavir/lamivudine as part of standard HIV care will continue taking their therapy.

TAF/FTC Cohort

Persons on tenofovir alafenamide/emtricitabine-containing therapy as part of their standard HIV care will continue to take their prescribed HIV medications.

Participants will be on study for 4 weeks, and will participate in directly observed therapy for the 4 weeks leading up to a single blood draw.

Blood collection

Intervention Type OTHER

Blood will be collected from participants at defined time points during the study to measure drug levels and assess platelet activity.

Tenofovir alafenamide/emtricitabine

Intervention Type DRUG

Participants who are already taking tenofovir alafenamide/emtricitabine as part of standard HIV care will continue taking their therapy.

Switch Cohort

Persons switching from abacavir/lamivudine-containing therapy as part of their standard HIV care will change to their newly prescribed regimen.

Participants will be on study for 3 weeks, and will have blood drawn at Days 0, 1, 3, 7, 10, 14, 18, and 21 following their switch.

Blood collection

Intervention Type OTHER

Blood will be collected from participants at defined time points during the study to measure drug levels and assess platelet activity.

Switch

Intervention Type DRUG

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.

Interventions

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Blood collection

Blood will be collected from participants at defined time points during the study to measure drug levels and assess platelet activity.

Intervention Type OTHER

Abacavir/lamivudine

Participants who are already taking abacavir/lamivudine as part of standard HIV care will continue taking their therapy.

Intervention Type DRUG

Tenofovir alafenamide/emtricitabine

Participants who are already taking tenofovir alafenamide/emtricitabine as part of standard HIV care will continue taking their therapy.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

ABC/3TC Cohort:

* On abacavir 600 mg/lamivudine 300 mg-containing regimen as part of their ART for at least 6 months prior to entry
* HIV-1 RNA \<200 copies/mL at screening and within the previous 6 months

TAF/FTC Cohort:

* On tenofovir alafenamide 25 mg/emtricitabine 200 mg-containing regimen as part of standard care for at least 6 months prior to entry
* HIV-1 RNA \<200 copies/mL at screening and within the previous 6 months

Switch Cohort:

\- Switching from an abacavir/lamivudine-containing regimen (to any other ART regimen not containing ABC/3TC) as part of standard care as recommended by their HIV provider

Exclusion Criteria

* eGFR \<50 mL/min/1.73 m2
* Platelet count \<100,000 cells/mm3
* Current or previous use (within 30 days) of anticoagulant or antiplatelet medications (e.g., aspirin, P2Y12 inhibitors, vitamin K antagonists, anti-Xa inhibitors, thrombin inhibitors, etc.)
* History of cardiovascular event(s) (e.g., myocardial infarction, cerebrovascular accident (stroke), peripheral arterial thrombosis, etc.), platelet or bleeding disorders
* Pregnant or planning pregnancy
* Any uncontrolled medical, social, or mental-health issue(s) that, in the opinion of the investigators, could interfere with study participation or the study outcomes
* Inability to comply with directly observed dosing (i.e., lack of availability or ability to use video streaming technology)
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Colorado, Denver

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kristina M Brooks, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

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University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Countries

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United States

Other Identifiers

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18-2749

Identifier Type: -

Identifier Source: org_study_id

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