HIVPhase 4NCT02924389
Dolutegravir in Reservoirs
A Phase 4 study testing dolutegravir, Triumeq and Truvada in people with HIV, run by Emory University at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV
- What is being tested?
- dolutegravir, Triumeq and Truvada
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2016to 11 Sep 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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)
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Grady Health System
Atlanta, Georgia, 30303
Ponce De Leon Center
Atlanta, Georgia, 30308
Emory University
Atlanta, Georgia, 30322
About this study
Official title: Defining Antiretroviral Pharmacology Within HIV-1 Reservoirs of Males and Females
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.
Read the detailed description
Emerging evidence indicates that sites outside of blood plasma, such as peripheral blood mononuclear cells (PBMCs) and gut-associated lymphoid tissue, remain reservoirs for HIV and play critical roles in viral persistence despite long-term potent combination antiretroviral therapy (cART). Suboptimal ARV drug concentrations within these reservoirs are thought to contribute to our inability to fully eradicate HIV. In addition, host factors such as sex have been found to impact ARV drug exposure within these sites and effect key outcomes such as time to virologic suppression. The understanding of reservoir site pharmacology and the impact on sex is limited due to several barriers: 1) Difficulty in sampling reservoir sites intensively and 2) Scarcity of women enrolled in HIV clinical research studies. Optimal drug concentrations are ideally determined early in drug development by dose-ranging studies that require intensive blood plasma sampling; this methodology is impractical to employ within tissue sites. To mitigate these barriers, the researchers propose to study the pharmacology of the integrase strand transfer inhibitor dolutegravir (DTG) within three body compartments: blood plasma, PBMCs, and rectal tissue using a novel integrated population pharmacokinetic-viral dynamic (PK-VD) modeling approach. This PK-VD modeling strategy generates concentration-response relationships with limited sampling and dosing simulations ideally suited to reservoir sites.
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.
- Conditions
- HIV
- Being tested
- dolutegravir, Triumeq, Truvada
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dolutegravirDrug
Also called Tivicay
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.
TriumeqDrug
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.
TruvadaDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: dolutegravir; Drug: Triumeq; Drug: Truvada |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Day 84 (hour 0 through 24)
Secondary outcomes (2)
Dolutegravir Exposure in Peripheral Blood Mononuclear Cells (PBMC)
Dolutegravir concentrations in peripheral blood mononuclear cells required for HIV viral load decline.
Measured: Up to Day 84
Dolutegravir Concentration in Rectal Tissue
Rectal dolutegravir concentrations in rectal tissue stratified by virologic suppressors vs non-suppressors.
Measured: Week 2, Week 6, Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2016 (estimated)
- Study startSep 2016
- Primary completion11 Sep 2019
- Study completion11 Sep 2019
Why it stopped: This study terminated early due to the ongoing covid-19 pandemic making it unsafe to recruit participants for in-person visits. Participants are living with HIV who are antiretroviral therapy-naive and are at high risk of COVID-19 complications.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Cecile Delille Lahiri, Emory University
- Investigators
- Cecile Lahiri, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02924389
- Sponsor's protocol ID
- IRB00089025
- Other IDs
- K23AI124913
- Status last verified
- Dec 2022
- First submitted
- 4 Oct 2016
- Last updated
- 29 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 30005011
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defining Antiretroviral Pharmacology Within HIV-1 Reservoirs of Males and Females
- ClinicalTrials.gov ID
- NCT02924389
- Acronym / sponsor ID
- IRB00089025
- Conditions
- HIV
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study terminated early due to the ongoing covid-19 pandemic making it unsafe to recruit participants for in-person visits. Participants are living with HIV who are antiretroviral therapy-naive and are at high risk of COVID-19 complications.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Sep 2016 (actual)
- Primary completion
- 11 Sep 2019 (actual)
- Study completion
- 11 Sep 2019 (actual)
- First posted
- 5 Oct 2016 (estimated)
- Results
- Posted 29 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Emerging evidence indicates that sites outside of blood plasma, such as peripheral blood mononuclear cells (PBMCs) and gut-associated lymphoid tissue, remain reservoirs for HIV and play critical roles in viral persistence despite long-term potent combination antiretroviral therapy (cART). Suboptimal ARV drug concentrations within these reservoirs are thought to contribute to our inability to fully eradicate HIV. In addition, host factors such as sex have been found to impact ARV drug exposure within these sites and effect key outcomes such as time to virologic suppression. The understanding of reservoir site pharmacology and the impact on sex is limited due to several barriers: 1) Difficulty in sampling reservoir sites intensively and 2) Scarcity of women enrolled in HIV clinical research studies. Optimal drug concentrations are ideally determined early in drug development by dose-ranging studies that require intensive blood plasma sampling; this methodology is impractical to employ within tissue sites. To mitigate these barriers, the researchers propose to study the pharmacology of the integrase strand transfer inhibitor dolutegravir (DTG) within three body compartments: blood plasma, PBMCs, and rectal tissue using a novel integrated population pharmacokinetic-viral dynamic (PK-VD) modeling approach. This PK-VD modeling strategy generates concentration-response relationships with limited sampling and dosing simulations ideally suited to reservoir sites.
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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anti-retroviral (ARV) Naïve Males | Other | Drug: dolutegravir, Drug: Triumeq, Drug: TruvadaMales 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. |
| Anti-retroviral (ARV) Naïve Females | Other | Drug: dolutegravir, Drug: Triumeq, Drug: TruvadaFemales 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dolutegravirAlso: TivicayTivicay 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. | Drug | Anti-retroviral (ARV) Naïve Females, Anti-retroviral (ARV) Naïve Males |
| TriumeqTriumeq 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 | Anti-retroviral (ARV) Naïve Females, Anti-retroviral (ARV) Naïve Males |
| TruvadaTruvada 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. | Drug | Anti-retroviral (ARV) Naïve Females, Anti-retroviral (ARV) Naïve Males |
Primary outcome
Dolutegravir Concentration
Time frame: Day 84 (hour 0 through 24)
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.
Time of Maximum Dolutegravir Concentration
Time frame: Day 84 (hour 0 through 24)
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.
Area Under the Dolutegravir Plasma Concentration vs Time Curve
Time frame: Day 84 (hour 0 through 24)
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.
2 secondary outcomes
Dolutegravir Exposure in Peripheral Blood Mononuclear Cells (PBMC)
Time frame: Up to Day 84
Dolutegravir Concentration in Rectal Tissue
Time frame: Week 2, Week 6, Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30005011Lahiri 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cecile Lahiri, MD principal investigator
Emory University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing dolutegravir, Triumeq and Truvada in people with HIV, run by Emory University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dolutegravir Concentration (time frame: Day 84 (hour 0 through 24)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02924389, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2022.