Dolutegravir in Reservoirs

NCT02924389 | Terminated Phase 4 Results FDA Drug

• 2 other identifiers: IRB00089025K23AI124913
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

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, as an exploratory aim, 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.

Conditions

HIV

Outcome Measures

Primary Outcomes (3)

• Dolutegravir Concentration

  Dolutegravir concentrations in blood plasma are assessed as the maximum dolutegravir concentration (Cmax) and 24 hour trough (lowest) concentration (C24h) of dolutegravir in micrograms per milliliter (µg/mL). Blood samples for pharmacokinetics were obtained prior to dosing (hour 0) and 1, 2, 3, 4, 6, 8, and 24 hours after dosing.

  Day 84 (hour 0 through 24)

• Time of Maximum Dolutegravir Concentration

  Time of maximum dolutegravir concentration is assessed in hours for the time periods of after the first dose and during steady state. Blood samples for pharmacokinetics were obtained prior to dosing (hour 0) and 1, 2, 3, 4, 6, 8, and 24 hours after dosing.

  Day 84 (hour 0 through 24)

• Area Under the Dolutegravir Plasma Concentration vs Time Curve

  The area under the dolutegravir plasma concentration vs time curve in a 24 hour period (AUC24h) is assessed in hours times micrograms per millimeters (h\* µg/mL) for the time periods of after the first dose and during steady state. Blood samples for pharmacokinetics were obtained prior to dosing (hour 0) and 1, 2, 3, 4, 6, 8, and 24 hours after dosing.

  Day 84 (hour 0 through 24)

Secondary Outcomes (2)

• Dolutegravir Exposure in Peripheral Blood Mononuclear Cells (PBMC)

  Up to Day 84

• Dolutegravir Concentration in Rectal Tissue

  Week 2, Week 6, Week 12

Study Arms (2)

Anti-retroviral (ARV) Naïve Males

OTHER

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 with dolutegravir.

Drug: dolutegravir; Drug: Triumeq; Drug: Truvada

Anti-retroviral (ARV) Naïve Females

OTHER

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 with dolutegravir.

Drug: dolutegravir; Drug: Triumeq; Drug: Truvada

Interventions

dolutegravir DRUG

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.

Also known as: Tivicay

Anti-retroviral (ARV) Naïve Females; Anti-retroviral (ARV) Naïve Males

Triumeq DRUG

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.

Anti-retroviral (ARV) Naïve Females; Anti-retroviral (ARV) Naïve Males

Truvada DRUG

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.

Anti-retroviral (ARV) Naïve Females; Anti-retroviral (ARV) Naïve Males

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• No ARVs in the last 6 months (from date of screening)
• No documented or suspected resistance to integrase inhibitors (dolutegravir, elvitegravir, raltegravir, or bictegravir).
• 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, DepoProvera, 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)

You may not qualify if:

• Pregnant or attempting to conceive now or during the course of the study
• Self-reported or documented current anal or rectal disease prohibiting safe anoscopy and biopsies, in investigator's opinion.
• 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

Sponsors & Collaborators

• Emory University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (3)

Grady Health System

Atlanta, Georgia, 30303, United States

Location

Ponce De Leon Center

Atlanta, Georgia, 30308, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Lahiri CD, Brown NL, Ryan KJ, Acosta EP, Sheth AN, Mehta CC, Ingersoll J, Ofotokun I. HIV RNA persists in rectal tissue despite rapid plasma virologic suppression with dolutegravir-based therapy. AIDS. 2018 Sep 24;32(15):2151-2159. doi: 10.1097/QAD.0000000000001945.

  PMID: 30005011 RESULT

MeSH Terms

Interventions

dolutegravir; abacavir, dolutegravir, and lamivudine drug combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Cecile Lahiri, MD
• Organization: Emory University

cdelill@emory.edu

404-616-6306

Study Officials

• Cecile Lahiri, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 4, 2016
• First Posted: October 5, 2016
• Study Start: September 1, 2016
• Primary Completion: September 11, 2019
• Study Completion: September 11, 2019
• Last Updated: December 29, 2022
• Results First Posted: December 29, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)