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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

About this trial

This is an interventional treatment trial for HIV Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Studies a U.S. FDA-regulated Device Product

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

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: