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Dolutegravir in Reservoirs

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ClinicalTrials.gov Identifier: NCT02924389
Recruitment Status : Recruiting
First Posted : October 5, 2016
Last Update Posted : October 11, 2018
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Cecile Delille Lahiri, Emory University

Brief Summary:
The purpose of this study is to find out how well the HIV medication dolutegravir gets into different parts of the body: including blood plasma, special blood cells, and rectal tissue. Specifically, investigators want to compare how fast dolutegravir lowers the HIV viral load in these three different sites. In addition, investigators seek to learn if there are any differences in how dolutegravir acts in males and females. Results of this study will provide more information about HIV medications and their limitations. In the future, this could help create better HIV medications that can get into these hard-to-reach places and eventually cure HIV infection.

Condition or disease Intervention/treatment Phase
HIV Drug: dolutegravir Drug: Triumeq Drug: Truvada Not Applicable

Detailed Description:

The purpose of this study is to find out how well the HIV medication dolutegravir gets into different parts of the body: including blood plasma, special blood cells, and rectal tissue. Specifically, investigators want to compare how fast dolutegravir lowers the HIV viral load in these three different sites. In addition, investigators seek to learn if there are any differences in how dolutegravir acts in males and females. Results of this study will provide more information about HIV medications and their limitations. In the future, this could help create better HIV medications that can get into these hard-to-reach places and eventually cure HIV infection.

The primary aim of this study is to validate the integrated population PK-VD model that quantitatively describes the relationship between dolutegravir (DTG) exposure and HIV viral decay in blood plasma. The second aim of this study is to develop an integrated population pharmacokinetic-viral dynamic (PK-VD) model to describe the relationship between DTG exposure and HIV viral decay in peripheral blood mononuclear cells and rectal tissue reservoir sites. The third aim is exploratory and will investigate sex differences in DTG penetration into blood plasma, peripheral blood mononuclear cells and rectal tissue reservoirs reservoirs as well as its impact on the rectal microbiome.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Defining Antiretroviral Pharmacology Within HIV-1 Reservoirs of Males and Females
Study Start Date : September 2016
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Anti-retroviral (ARV) Naïve Males
Males diagnosed with HIV will undergo serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Participants will be treated with either Triumeq or Truvada and dolutegravir.
Drug: dolutegravir
Tivicay is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. 50 mg of Tivicay (dolutegravir) will be taken orally once a day in combination with Truvada.
Other Name: Tivicay

Drug: Triumeq
Triumeq is a fixed-dose combination drug for the treatment of HIV/AIDS. It is a combination of 600 mg abacavir, 50 mg dolutegravir and 300 mg lamivudine. Triumeq will be taken orally once daily.

Drug: Truvada
Truvada is a combination of emtriva and viread, both nucleoside analog HIV-1 reverse transcriptase inhibitors. Truvada is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. One Truvada tablet (containing 200 mg/300 mg of emtricitabine and tenofovir disoproxil fumarate) will be taken orally once daily in combination with Tivicay (dolutegravir).

Anti-retroviral (ARV) Naïve Females
Females diagnosed with HIV will undergo serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Participants will be treated with either Triumeq or Truvada and dolutegravir.
Drug: dolutegravir
Tivicay is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. 50 mg of Tivicay (dolutegravir) will be taken orally once a day in combination with Truvada.
Other Name: Tivicay

Drug: Triumeq
Triumeq is a fixed-dose combination drug for the treatment of HIV/AIDS. It is a combination of 600 mg abacavir, 50 mg dolutegravir and 300 mg lamivudine. Triumeq will be taken orally once daily.

Drug: Truvada
Truvada is a combination of emtriva and viread, both nucleoside analog HIV-1 reverse transcriptase inhibitors. Truvada is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. One Truvada tablet (containing 200 mg/300 mg of emtricitabine and tenofovir disoproxil fumarate) will be taken orally once daily in combination with Tivicay (dolutegravir).




Primary Outcome Measures :
  1. Maximum Dolutegravir Concentration in Blood Plasma [ Time Frame: Up to Day 84 ]
    The maximum dolutegravir concentration in blood plasma required to produce 90% of the maximum drug effect.


Secondary Outcome Measures :
  1. Maximum Dolutegravir Concentration in Peripheral Blood Mononuclear Cells [ Time Frame: Up to Day 84 ]
    The maximum dolutegravir concentration in peripheral blood mononuclear cells required to produce 90% of the maximum drug effect.

  2. Maximum Dolutegravir Concentration in Rectal Tissue [ Time Frame: Up to Day 84 ]
    The maximum dolutegravir concentration in rectal tissue required to produce 90% of the maximum drug effect.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Antiretroviral naïve. Participants will be classified as ARV-naïve if they meet any of the following criteria: 1) No ARVs for ≥ 6 months and never taken HIV medications for ≥ 30 consecutive days, 2) Females that only took ARVs during pregnancy and have been off ARVs for ≥ 6 months prior to enrollment, or 3) Persons whose only exposure to ARVs was "monotherapy"(meaning they were taking only one class of ARVs) before the advent of HAART.
  • Plasma HIV-1 RNA >1000 copies/mL
  • Creatinine Clearance >50 mL/min, as calculated by the Cockcroft-Gault equation within 90 days of screen
  • Liver function testing, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase < 5 times upper limit of normal within 90 days of screen
  • Intact gastrointestinal tract
  • Able and willing to give informed consent
  • Willing and eligible to initiate ARV therapy with Triumeq, DTG + Truvada (TDF/FTC), or DTG + Descovy (FTC/TAF)
  • Agree to receive from their provider and pay for a prescribed supply of the drug, Tivicay® (dolutegravir/DTG), with either Triumeq, or Truvada or Descovy as determined by their primary HIV provider.

    • Agree to take the prescribed medication by mouth.
    • Agree that they (the participant) is responsible for bringing these medications with them to their study visits.
  • Willing to undergo serial blood and rectal tissue sampling
  • Female participants' must be willing to have a pregnancy test done at each visit.

Female participants of childbearing potential (FCB) must agree to either commit to continued abstinence from heterosexual intercourse or to use a reliable form of birth control such as oral contraceptive pills, intrauterine device, Nexplanon, Depo Provera, permanent sterilization, or another acceptable method, as determined by the investigator for the duration of the study. FCB are defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy or have not been naturally postmenopausal for at least 24 consecutive months (i.e have had menses at any time in preceding 24 months)

Exclusion Criteria:

  • Pregnant or attempting to conceive now or during the course of the study
  • Palpable abnormality on digital rectal exam
  • Severe perianal disease requiring surgery or prohibiting the ability to safely perform anoscopy with biopsies, in investigator's opinion
  • Taking concurrent medications that interfere with DTG (see Table 2)
  • Bleeding diathesis
  • Platelet count <50,000 mm3
  • Medical condition that interferes with conduct of study, in investigator's opinion

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02924389


Contacts
Contact: Cecile Lahiri, MD 404-616-6306 cdelill@emory.edu

Locations
United States, Georgia
Grady Health System Recruiting
Atlanta, Georgia, United States, 30303
Contact: Cecile Lahiri, MD    404-616-6306    cdelill@emory.edu   
Ponce De Leon Center Recruiting
Atlanta, Georgia, United States, 30308
Contact: Cecile Lahiri, MD    404-616-6306    cdelill@emory.edu   
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Cecile Lahiri, MD    404-616-6306    cdelill@emory.edu   
Sponsors and Collaborators
Emory University
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Cecile Lahiri, MD Emory University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Cecile Delille Lahiri, Associate Professor, Emory University
ClinicalTrials.gov Identifier: NCT02924389     History of Changes
Other Study ID Numbers: IRB00089025
K23AI124913 ( U.S. NIH Grant/Contract )
First Posted: October 5, 2016    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018

Additional relevant MeSH terms:
Dolutegravir
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Anti-Retroviral Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors