Triple vs. Double Therapy in naïves HIV-Infected Patients

Phase 4

• Conditions: HIV Infection
• Interventions: Drug: Randomize

• Registration Number: NCT04295460
• Lead Sponsor: Hospitales Universitarios Virgen del Rocío

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-03-02
• Study First Submitted QC: 2020-03-02
• Study First Posted: 2020-03-04
• Study Start: 2020-03-10
• Status Verified: 2020-08
• Last Update Submitted: 2020-08-14
• Last Update Posted: 2020-08-18
• Primary Completion: 2022-01
• Study Completion: 2023-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 70

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dual Therapy	Randomize	Dolutegravir plus lamivudine
Triple Therapy	Randomize	Dolutegravir plus TAF/FTC

Primary Outcome Measures

Name	Time	Method
proviral HIV-DNA	48 and 96 weeks	Mean changes in proviral HIV-DNA in PBMCs after 48 and 96 weeks of treatment

Secondary Outcome Measures

Name	Time	Method
Immune Recovery	48 and 96 weeks	Mean changes immune recovery assessed by CD4+/CD8+ T cell ratio.
Monocytes Activation	48 and 96 weeks	Mean changes monocytes activation (plasma sCD14 and sCD163).
Immunosenescense	48 and 96 weeks	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	48 and 96 weeks	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.
Immune Activation	48 and 96 weeks	Mean changes immune activation assessed by the expression of HLA-DR and CD38 in both of CD4+ and CD8+ T cells.
Viral Reservoir	48 and 96 weeks	Mean changes viral reservoir size, evaluated by proviral HIV-DNA and HIV-RNA in peripheral blood mononuclear cells (PBMC) and CD4+ T cells isolate.

Trial Locations

Locations (1)

Hospital Universitario Virgen del Rocio; 🇪🇸 Seville, Spain