Triple vs. Double Therapy in naïves HIV-Infected Patients

HIV Infection Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04295460
• Other study ID #: FIS-TAR-01-2019
• Status: Recruiting
• Phase: Phase 4
• Start date: March 10, 2020
• Est. completion date: March 2023

Study information

• Verified date: August 2020
• Source: Hospitales Universitarios Virgen del Rocío
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: March 2023
• Est. primary completion date: January 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

Drug:
• Randomize
Randomize to naive-treatment HIV-infected patients to receive dual o triple therapy as initial antiretroviral treatment

Locations

Country	Name	City	State
Spain	Hospital Universitario Virgen del Rocio	Seville

Sponsors (1)

Lead Sponsor	Collaborator
Hospitales Universitarios Virgen del Rocío

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Semen	Mean changes of HIV-RNA seminal plasma viral load	24 weeks
Other	GALT	Mean changes of viral reservoir assessed as proviral HIV-DNA and HIV-RNA in GALT	48 weeks
Primary	proviral HIV-DNA	Mean changes in proviral HIV-DNA in PBMCs after 48 and 96 weeks of treatment	48 and 96 weeks
Secondary	Immune Recovery	Mean changes immune recovery assessed by CD4+/CD8+ T cell ratio.	48 and 96 weeks
Secondary	Immune Activation	Mean changes immune activation assessed by the expression of HLA-DR and CD38 in both of CD4+ and CD8+ T cells.	48 and 96 weeks
Secondary	Monocytes Activation	Mean changes monocytes activation (plasma sCD14 and sCD163).	48 and 96 weeks
Secondary	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.	48 and 96 weeks
Secondary	Inflammation	Mean changes concentration of pro-inflammatory soluble mediator in plasma: TNF-a, IL-1ß, IL-6, IP-10, IFN- ?, MIP-1a, MIP-1ß, hsPCR y D-dímers.	48 and 96 weeks
Secondary	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.	48 and 96 weeks