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Completed

NCT Number: NCT04079452

Doravirine Concentrations and Antiviral Activity in Cerebrospinal Fluid in HIV-1 Infected Individuals

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.

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Key information

Conditions

HIV-1-infection

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

About this study

15 asymptomatic, virologically suppressed, HIV infected patients will be offered to switch their antiretroviral treatment to Doravirine+Emtricitabine/TAF. After 4 weeks of treatment all subjects will undergo lumbar puncture and bloods in order to assess CSF and plasma (total and unbound) Doravirine concentrations. HIV RNA also will be assessed. All subjects will complete a follow up visit 4 weeks after

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Asymptomatic, HIV-1 infected individuals ≥ 18 years of age
  • 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.
  • Plasma HIV-1 RNA at screening <40 copies/mL for at least 3 months at the Screening visit.
  • Signed and dated written informed consent prior to inclusion.
  • 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

  • Severe hepatic impairment (Child-Pugh Class C)
  • Ongoing malignancy
  • Active opportunistic infection
  • 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.
  • Any verified Grade 4 laboratory abnormality
  • ALT or AST ≥ 3xULN and/or bilirubin ≥ 1.5xULN
  • Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min
  • Females who are pregnant (as confirmed by positive serum pregnancy test) or breastfeeding.
  • Current treatment with antiaggregant or anticoagulant therapy.
  • History of any neurologic disease/condition/treatment may alter the blood brain barrier permeability.

Treatment and study plan

Doravirine

Drug

Doravirine 100 mg tablet

Other names: MK-1439

Descovy

Drug

Tenofovir alafenamide 25 mg / emtricitabine 200 mg tablet

Other names: TAF/FTC

Primary outcomes

  1. Total Doravirine Concentrations in Cerebrospinal Fluid

    Time frame: 4 Weeks

    Total Doravirine concentrations in cerebrospinal fluid in HIV-1 infected individual receiving ART with Doravirine+FTC/TAF

  2. Total Doravirine Concentrations in Blood Plasma

    Time frame: 4 Weeks

    Total Doravirine concentrations in blood plasma

  3. Total Doravirine Concentration CSF/Plasma Ratio

    Time frame: 4 Weeks

    total Doravirine CSF/plasma ratio

  4. HIV-1 RNA in Cerebrospinal Fluid

    Time frame: 4 Weeks

    Number of patients with HIV-1 RNA cerebrospinal fluid <40 copies/ml

  5. HIV-1 RNA in Blood Plasma

    Time frame: 4 Weeks

    Number of patients with HIV-1 RNA in blood plasma <40 copies/ml

  6. Unbound Doravirine Concentrations in CSF

    Time frame: 4 Weeks

    Unbound Doravirine concentrations in cerebrospinal fluid in HIV-1 infected individual receiving ART with Doravirine+FTC/TAF

  7. Doravirine Concentrations in Blood Plasma

    Time frame: 4 Weeks

    Unbound Doravirine concentrations in blood plasma

  8. Unbound Doravirine Concentration CSF/Plasma Ratio

    Time frame: 4 Weeks

    Unbound Doravirine CSF/plasma ratio

Sponsors and collaborators

Lead sponsor

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Other

Collaborators

  • Hospital Universitari de Bellvitge
  • Institut d'Investigació Biomèdica de Bellvitge

Registry information

Important dates

Study start
2020
Primary completion
2020
Study completion
2020
First posted
Sep 6, 2019
Registry last updated
Apr 28, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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