HIV-1-infectionNCT04301661
Cellular Pharmacology and Platelet Effects of Abacavir and Lamivudine Anabolites
An observational study of HIV-1-infection, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- Blood collection, Abacavir/lamivudine and Tenofovir alafenamide/emtricitabine
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Mar 2020to 17 Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Hospital
Aurora, Colorado, 80045
About this study
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.
Read the 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
- Being tested
- Blood collection, Abacavir/lamivudine, Tenofovir alafenamide/emtricitabine, Switch
- Keywords
- NRTI, platelet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood collectionOther
Blood will be collected from participants at defined time points during the study to measure drug levels and assess platelet activity.
Abacavir/lamivudineDrug
Participants who are already taking abacavir/lamivudine as part of standard HIV care will continue taking their therapy.
Tenofovir alafenamide/emtricitabineDrug
Participants who are already taking tenofovir alafenamide/emtricitabine as part of standard HIV care will continue taking their therapy.
SwitchDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Other: Blood collection; Drug: Switch |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: (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.
Measured: (Days 0, 1, 3, 7, 10, 14, 18, 21 in Switch Cohort)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2020
- Study start6 Mar 2020
- Primary completion17 Dec 2021
- Study completion17 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kristina M Brooks, PharmD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04301661
- Sponsor's protocol ID
- 18-2749
- Status last verified
- Jan 2023
- First submitted
- 2 Mar 2020
- Last updated
- 9 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cellular Pharmacology and Platelet Effects of Abacavir and Lamivudine Anabolites
- ClinicalTrials.gov ID
- NCT04301661
- Acronym / sponsor ID
- 18-2749
- Conditions
- HIV-1-infection
- Keywords
- NRTI, platelet
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 6 Mar 2020 (actual)
- Primary completion
- 17 Dec 2021 (actual)
- Study completion
- 17 Dec 2021 (actual)
- First posted
- 10 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ABC/3TC Cohort | – | Other: Blood collection, Drug: Abacavir/lamivudinePersons 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. |
| TAF/FTC Cohort | – | Other: Blood collection, Drug: Tenofovir alafenamide/emtricitabinePersons 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. |
| Switch Cohort | – | Other: Blood collection, Drug: SwitchPersons 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (8 listed)
- 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
- 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
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood collectionBlood will be collected from participants at defined time points during the study to measure drug levels and assess platelet activity. | Other | ABC/3TC Cohort, Switch Cohort, TAF/FTC Cohort |
| Abacavir/lamivudineParticipants who are already taking abacavir/lamivudine as part of standard HIV care will continue taking their therapy. | Drug | ABC/3TC Cohort |
| Tenofovir alafenamide/emtricitabineParticipants who are already taking tenofovir alafenamide/emtricitabine as part of standard HIV care will continue taking their therapy. | Drug | TAF/FTC Cohort |
| SwitchParticipants 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. | Drug | Switch Cohort |
Primary outcome
Intracellular steady-state concentrations of abacavir and lamivudine anabolites in RBCs (also measured in DBS), PBMCs, platelets, and neutrophils.
Time frame: (Week 4 in ABC/3TC and TAF/FTC Cohorts)
Based on drug concentrations measured at week 4
Intracellular half-lives of abacavir and lamivudine anabolites in RBCs (also measured in DBS), PBMCs, platelets, and neutrophils.
Time frame: (Days 0, 1, 3, 7, 10, 14, 18, 21 in Switch Cohort)
Based on decline in drug concentrations between days 0 and 21.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristina M Brooks, PharmD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV-1-infection, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intracellular steady-state concentrations of abacavir and lamivudine anabolites in RBCs (also measured in DBS), PBMCs, platelets, and neutrophils. (time frame: (Week 4 in ABC/3TC and TAF/FTC Cohorts)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2023.