Triple vs. Double Therapy in naïves HIV-Infected Patients (TRIDUNA)
Primary Purpose
HIV Infection
Status
Unknown status
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Randomize
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infection
Eligibility Criteria
Inclusion Criteria:
- Treatment-naïve HIV-1-infected patients ≥ 18 years of age.
- Plasma HIV-1 RNA >5000 and <500.000 copies/ml.
- T lymphocyte CD4+ count in peripheral blood >200/μl.
Patients of childbearing age should consent to use a highly effective contraceptive method from 15 days before the time of inclusion of the study until 30 days after the end of it. It is considered a highly effective method:
- Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of Investigational Product, throughout the study, and for at least 2 weeks after discontinuation of all study medications;
- Any intrauterine device with published data showing that the expected failure rate is <1% per year (not all intrauterine devices meet this criterion)
- Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject.
- Approved hormonal contraception.
- Any other method with published data showing that the expected failure rate is <1% per year.
- Signed written informed consent prior to inclusion.
Exclusion Criteria:
- Acute HIV infection
- T lymphocyte CD4+ count in peripheral blood ≤ 200/µl
- Active opportunistic infection.
- Pregnancy at inclusion or during the follow-up
- Active hepatitis C and/or B virus co-infection.
- ALT ≥ 5 times the ULN, or ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin).
- Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones).
- Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
- Current or past disease that requires the use subsidiary of treatment with corticosteroids, immunomodulatory agents, interferon or chemotherapeutic agents.
- Any laboratory abnormality grade 3 or 4 according to the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (Annex 3)
- Concomitant use of drugs with potential major interactions with the prescribed drugs according to the respective full prescribing information.
- Estimated creatinine clearance <50ml/min.
- History or presence of allergy to the study drugs or their components
Sites / Locations
- Hospital Universitario Virgen del RocioRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Dual Therapy
Triple Therapy
Arm Description
Dolutegravir plus lamivudine
Dolutegravir plus TAF/FTC
Outcomes
Primary Outcome Measures
proviral HIV-DNA
Mean changes in proviral HIV-DNA in PBMCs after 48 and 96 weeks of treatment
Secondary Outcome Measures
Immune Recovery
Mean changes immune recovery assessed by CD4+/CD8+ T cell ratio.
Immune Activation
Mean changes immune activation assessed by the expression of HLA-DR and CD38 in both of CD4+ and CD8+ T cells.
Monocytes Activation
Mean changes monocytes activation (plasma sCD14 and sCD163).
Immunosenescense
Mean changes expression of markers for recent thymic emigrants (CD31), proliferation (Ki67), dysfunction (PD-1), senescence (CD57), and apoptosis (annexin A) in both CD4+ and CD8+ T cells.
Inflammation
Mean changes concentration of pro-inflammatory soluble mediator in plasma: TNF-α, IL-1β, IL-6, IP-10, IFN- γ, MIP-1α, MIP-1β, hsPCR y D-dímers.
Viral Reservoir
Mean changes viral reservoir size, evaluated by proviral HIV-DNA and HIV-RNA in peripheral blood mononuclear cells (PBMC) and CD4+ T cells isolate.
Full Information
NCT ID
NCT04295460
First Posted
March 2, 2020
Last Updated
August 14, 2020
Sponsor
Hospitales Universitarios Virgen del Rocío
1. Study Identification
Unique Protocol Identification Number
NCT04295460
Brief Title
Triple vs. Double Therapy in naïves HIV-Infected Patients
Acronym
TRIDUNA
Official Title
Effectiveness of a Dual Therapy (Dolutegravir + Lamivudine) on Reduction of the Viral Reservoir, Immune Recovery and Immune Activation Compared With a Triple Therapy (Dolutegravir + Tenofovir Alafenamide/Emtricitabine) in Treatment-naïve HIV-Infected Patients
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Unknown status
Study Start Date
March 10, 2020 (Actual)
Primary Completion Date
January 2022 (Anticipated)
Study Completion Date
March 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hospitales Universitarios Virgen del Rocío
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The objective of this study is to clarify whether if starting antiretroviral treatment based on dual therapy (DTG + 3TC) could provide less control of residual HIV replication and, therefore, a detriment on immune activation and inflammation compared to starting with triple therapy, and could worsen the patients' long-term prognosis. For this purpose, the investigator has designed a randomized clinical trial where will assess the immunological recovery (CD4+/CD8+), immune activation, proliferation, senescence and apoptosis in T lymphocytes CD4+ and CD8+ cells by flow cytometry, the immune activation of monocytes/ macrophages and plasma concentrations of various inflammatory mediators by ELISAS, and the thymic function, the cellular reservoir of HIV and the degree of HIV DNA transcription by digital dropped PCR.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dual Therapy
Arm Type
Experimental
Arm Description
Dolutegravir plus lamivudine
Arm Title
Triple Therapy
Arm Type
Active Comparator
Arm Description
Dolutegravir plus TAF/FTC
Intervention Type
Drug
Intervention Name(s)
Randomize
Other Intervention Name(s)
Triple therapy
Intervention Description
Randomize to naive-treatment HIV-infected patients to receive dual o triple therapy as initial antiretroviral treatment
Primary Outcome Measure Information:
Title
proviral HIV-DNA
Description
Mean changes in proviral HIV-DNA in PBMCs after 48 and 96 weeks of treatment
Time Frame
48 and 96 weeks
Secondary Outcome Measure Information:
Title
Immune Recovery
Description
Mean changes immune recovery assessed by CD4+/CD8+ T cell ratio.
Time Frame
48 and 96 weeks
Title
Immune Activation
Description
Mean changes immune activation assessed by the expression of HLA-DR and CD38 in both of CD4+ and CD8+ T cells.
Time Frame
48 and 96 weeks
Title
Monocytes Activation
Description
Mean changes monocytes activation (plasma sCD14 and sCD163).
Time Frame
48 and 96 weeks
Title
Immunosenescense
Description
Mean changes expression of markers for recent thymic emigrants (CD31), proliferation (Ki67), dysfunction (PD-1), senescence (CD57), and apoptosis (annexin A) in both CD4+ and CD8+ T cells.
Time Frame
48 and 96 weeks
Title
Inflammation
Description
Mean changes concentration of pro-inflammatory soluble mediator in plasma: TNF-α, IL-1β, IL-6, IP-10, IFN- γ, MIP-1α, MIP-1β, hsPCR y D-dímers.
Time Frame
48 and 96 weeks
Title
Viral Reservoir
Description
Mean changes viral reservoir size, evaluated by proviral HIV-DNA and HIV-RNA in peripheral blood mononuclear cells (PBMC) and CD4+ T cells isolate.
Time Frame
48 and 96 weeks
Other Pre-specified Outcome Measures:
Title
Semen
Description
Mean changes of HIV-RNA seminal plasma viral load
Time Frame
24 weeks
Title
GALT
Description
Mean changes of viral reservoir assessed as proviral HIV-DNA and HIV-RNA in GALT
Time Frame
48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Treatment-naïve HIV-1-infected patients ≥ 18 years of age.
Plasma HIV-1 RNA >5000 and <500.000 copies/ml.
T lymphocyte CD4+ count in peripheral blood >200/μl.
Patients of childbearing age should consent to use a highly effective contraceptive method from 15 days before the time of inclusion of the study until 30 days after the end of it. It is considered a highly effective method:
Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of Investigational Product, throughout the study, and for at least 2 weeks after discontinuation of all study medications;
Any intrauterine device with published data showing that the expected failure rate is <1% per year (not all intrauterine devices meet this criterion)
Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject.
Approved hormonal contraception.
Any other method with published data showing that the expected failure rate is <1% per year.
Signed written informed consent prior to inclusion.
Exclusion Criteria:
Acute HIV infection
T lymphocyte CD4+ count in peripheral blood ≤ 200/µl
Active opportunistic infection.
Pregnancy at inclusion or during the follow-up
Active hepatitis C and/or B virus co-infection.
ALT ≥ 5 times the ULN, or ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin).
Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones).
Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
Current or past disease that requires the use subsidiary of treatment with corticosteroids, immunomodulatory agents, interferon or chemotherapeutic agents.
Any laboratory abnormality grade 3 or 4 according to the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (Annex 3)
Concomitant use of drugs with potential major interactions with the prescribed drugs according to the respective full prescribing information.
Estimated creatinine clearance <50ml/min.
History or presence of allergy to the study drugs or their components
Facility Information:
Facility Name
Hospital Universitario Virgen del Rocio
City
Seville
ZIP/Postal Code
41013
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luis F Lopez-Cortes, MD, PhD
Phone
34 - 955013096
Email
lflopez@us.es
First Name & Middle Initial & Last Name & Degree
Luis F Lopez-Cortes, MD, PhD
First Name & Middle Initial & Last Name & Degree
Alicia Gutierrez-Valencia, Pharm D
First Name & Middle Initial & Last Name & Degree
Pompeyo Viciana, MD, PhD
First Name & Middle Initial & Last Name & Degree
Rosa Ruiz-Valderas, MD, PhD
First Name & Middle Initial & Last Name & Degree
Juan R Castillo-Ferrando, MD, PhD
12. IPD Sharing Statement
Learn more about this trial
Triple vs. Double Therapy in naïves HIV-Infected Patients
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