Cellular Pharmacology and Platelet Effects of Abacavir and Lamivudine Anabolites
Condition: HIV-1-infection
Study type: Observational

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.
    

Intervention name(s): Blood collection; Abacavir/lamivudine; Tenofovir alafenamide/emtricitabine; Switch
Intervention type(s): Other; Drug; Drug; Drug
Intervention description(s): Blood will be collected from participants at defined time points during the study to measure drug levels and assess platelet activity.; Participants who are already taking abacavir/lamivudine as part of standard HIV care will continue taking their therapy.; Participants who are already taking tenofovir alafenamide/emtricitabine as part of standard HIV care will continue taking their therapy.; 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 MeSH terms: Tenofovir; Lamivudine; Emtricitabine; Abacavir
Observational model: Cohort
Time perspective: Prospective
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.
      
Biospecimen description: 
      Whole blood, plasma, PBMC, RBC, dried blood spot (DBS), platelets, neutrophils
    
Keywords: NRTI; platelet