Doravirine Concentrations and Antiviral Activity in Cerebrospinal Fluid in HIV-1 Infected Individuals
Condition: HIV-1-infection
Intervention: Doravirine; Descovy
Intervention description: Doravirine 100 mg tablet; Tenofovir alafenamide 25 mg / emtricitabine 200 mg tablet
Intervention MeSH terms: Emtricitabine tenofovir alafenamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Doravirine

Summary:

      Doravirine is a new HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) that has
      demonstrated a good efficacy and safety profile in clinical trials. It functions by
      inhibiting viral replication of both wild-type virus and most common NNRTI variants. It is
      dosed orally once daily and always given in combination with other HIV-1 active agents as
      part of highly active antiretroviral therapy. Initial pharmacokinetic studies demonstrated
      not extensive binding to plasma proteins, which may be crucial determinant for penetration to
      different reservoirs such as the central nervous system (CNS). This study will address two
      important issues: The pharmacokinetic profile of Doravirine in cerebrospinal fluid (CSF) as
      well as the maintenance of HIV suppression in CSF. The assessment of concentrations as well
      as the antiviral activity of new antiretroviral drugs in compartments such as CNS is relevant
      to avoid HIV-related neurocognitive disorders as well as for future cure strategies. In
      addition, the role of unbound ARV drug concentrations has been scarcely evaluated.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Asymptomatic, HIV-1 infected individuals ≥ 18 years of age

          2. Be on a stable ART continously or ≥3 consecutive months preceding the screening visit.
             Patients already receiving TAF/FTC+DoravirineC for at least three consecutive months
             will be eligible.

          3. Plasma HIV-1 RNA at screening <40 copies/mL for at least 3 months at the Screening
             visit.

          4. Signed and dated written informed consent prior to inclusion.

          5. Subjects must agree to utilize a highly effective method of contraception during
             heterosexual intercourse from the screening visit throughout the duration of the
             study.

        Exclusion Criteria:

          1. Severe hepatic impairment (Child-Pugh Class C)

          2. Ongoing malignancy

          3. Active opportunistic infection

          4. Primary resistance to any of the ARV included in the study or history of virologic
             failure with risk of resistance selection to any of the study drugs.

          5. Any verified Grade 4 laboratory abnormality

          6. ALT or AST ≥ 3xULN and/or bilirubin ≥ 1.5xULN

          7. Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min

          8. Females who are pregnant (as confirmed by positive serum pregnancy test) or
             breastfeeding.

          9. Current treatment with antiaggregant or anticoagulant therapy.

         10. History of any neurologic disease/condition/treatment may alter the blood brain
             barrier permeability.