Cellular Pharmacology and Platelet Effects of Abacavir and Lamivudine Anabolites

NCT04301661 | Completed FDA Drug

• 1 other identifier: 18-2749
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV-1-infection

Keywords

NRTI; platelet

Outcome Measures

Primary Outcomes (2)

• Intracellular steady-state concentrations of abacavir and lamivudine anabolites in RBCs (also measured in DBS), PBMCs, platelets, and neutrophils.

  Based on drug concentrations measured at week 4

  (Week 4 in ABC/3TC and TAF/FTC Cohorts)

• Intracellular half-lives of abacavir and lamivudine anabolites in RBCs (also measured in DBS), PBMCs, platelets, and neutrophils.

  Based on decline in drug concentrations between days 0 and 21.

  (Days 0, 1, 3, 7, 10, 14, 18, 21 in Switch Cohort)

Other Outcomes (2)

• Intracellular concentrations of endogenous nucleotides measured in platelets from patients on abacavir- or tenofovir-containing therapy.

  (Week 4 in ABC/3TC and TAF/FTC Cohorts; Days 0 and 21 in Switch Cohort)

• Intracellular endogenous metabolites measured in platelets from patients on abacavir- or tenofovir-containing therapy.

  (Week 4 in ABC/3TC and TAF/FTC Cohorts; Days 0 and 21 in Switch Cohort)

Study Arms (3)

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.

Other: Blood collection; Drug: Abacavir/lamivudine

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.

Other: Blood collection; Drug: Tenofovir alafenamide/emtricitabine

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.

Other: Blood collection; Drug: Switch

Interventions

Blood collection OTHER

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

ABC/3TC Cohort; Switch Cohort; TAF/FTC Cohort

Abacavir/lamivudine DRUG

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

ABC/3TC Cohort

Tenofovir alafenamide/emtricitabine DRUG

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

TAF/FTC Cohort

Switch 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.

Switch Cohort

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Persons living with HIV receiving either abacavir/lamivudine or tenofovir alafenamide/emtricitabine as part of standard HIV care, or planning a switch from an abacavir/lamivudine-containing regimen.

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma, PBMC, RBC, dried blood spot (DBS), platelets, neutrophils

MeSH Terms

Interventions

Blood Specimen Collection; abacavir, lamivudine drug combination; emtricitabine tenofovir alafenamide

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Kristina M Brooks, PharmD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 10, 2020
• Study Start: March 6, 2020
• Primary Completion: December 17, 2021
• Study Completion: December 17, 2021
• Last Updated: January 9, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)