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Dolutegravir in Reservoirs

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 by Emory University
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Cecile Delille Lahiri, Emory University
ClinicalTrials.gov Identifier:
NCT02924389
First received: October 4, 2016
Last updated: NA
Last verified: October 2016
History: No changes posted
  Purpose
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 Intervention
HIV
Drug: dolutegravir
Drug: Triumeq
Drug: Truvada

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Defining Antiretroviral Pharmacology Within HIV-1 Reservoirs of Males and Females

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • 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:
  • 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.

  • 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.


Estimated Enrollment: 40
Study Start Date: September 2016
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

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.

  Eligibility

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

Inclusion Criteria:

  • Antiretroviral (ARV) 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 highly active anti-retroviral therapy (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 or dolutegravir (DTG) and tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)
  • Willing to undergo serial blood and rectal tissue sampling

Exclusion Criteria:

  • Currently pregnant
  • Symptomatic rectal disease at time of screening
  • Currently taking concurrent medications that interfere with DTG
  • Bleeding diathesis
  • Platelet count <50,000 mm3
  • Medical condition that interferes with conduct of study, in investigator's opinion
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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 Institutes of Health (NIH)
Investigators
Principal Investigator: Cecile Lahiri, MD Emory University
  More Information

Responsible Party: Cecile Delille Lahiri, Associate Professor, Emory University
ClinicalTrials.gov Identifier: NCT02924389     History of Changes
Other Study ID Numbers: IRB00089025
Study First Received: October 4, 2016
Last Updated: October 4, 2016

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

ClinicalTrials.gov processed this record on May 25, 2017