Tripe Versus Dual Antiretroviral Therapy in HIV-infected Patients With Virological Suppression (Tridual)

NCT03447873 | Completed Phase 4 DMC

• 2 other identifiers: FIS-TAR-01-20162016-005226-11
• Study Type: interventional
• Target: 153
• Locations: 1 country
• Sites: 1

Brief Summary

The persistence of an aberrant state of immune activation and inflammation (pIA) may contribute to the emergence of serious non-AIDS events which carry a higher morbimortality in HIV-infected patients. Although combined antiretroviral treatment (cART) reduces both cellular and soluble activation markers, it fails to completely control pIA despite consistent plasma viral load suppression. One of the mechanisms involved in pIA is may be an incomplete suppression of viral replication not reflected by plasma viral load, which only reflects a balance between viral replication and clearance of HIV-RNA. In addition, low-level viremia detected in most HIV-1-infected patients despite years on cART. Unintegrated 2-LTR HIV-DNA, and cellular associated HIV-RNAs, as products of active integrated DNA transcription, support this issue. Furthermore, the key rationales behind simplifying cART are a reduction of toxicities, lower risk of resistance mutations in case of virological failure and saving costs. One of these simplification strategies is a dual therapy which, based on the data up to date and in our clinical experience, has similar virological efficacy than cART. However, it is unknown if this strategy could increase the persistent HIV-1 replication and, therefore, pIA. The CD4+/CD8+ T cell ratio as a marker of immune recovery, the changes in T cell immune activation, senescence, exhaustion and apoptosis, and the cellular associated HIV-DNA and -RNA would answer the question if simplification to dual therapy would provide less control of residual HIV replication and, therefore, a detriment on pIA compared to triple therapy and, therefore, would worsen the patients' long-term prognosis.

Conditions

HIV Infections

Keywords

Antiretroviral treatment; Treatment simplification; Dual therapy; Immune recovery

Outcome Measures

Primary Outcomes (1)

• CD4/CD8 ratio

  To evaluate if a triple therapy based on integrase inhibitors plus two nucleos(t)ide analogs will provide a higher CD4+/CD8+ T cell ratio recovery compared with dual therapies based on darunavir/cobicistat plus lamivudine or dolutegravir plus lamivudine after 48 weeks of treatment in HIV-infected patients with consistent plasma viral load suppression.

  48 weeks

Secondary Outcomes (1)

• Immune activation

  48 weeks

Study Arms (3)

Triple therapy

ACTIVE COMPARATOR

To Continue with triple therapy with Elvitegravir/cobicistat + tenofovir alafenamide + emtricitabine or Dolutegravir + abacavir + lamivudine once daily.

Drug: Continue with triple therapy

Switch to dual therapy A

EXPERIMENTAL

Switch to dual therapy with Darunavir/cobicistat (800150 mg) + lamivudine (300 mg) once daily once daily.

Drug: Switch to DTG + 3TC

Switch to dual therapy B

EXPERIMENTAL

Switch to dual therapy with Dolutegravir (50 mg) + lamivudine (300 mg) once daily

Drug: Switch to DRV/cobicistat + 3TC

Interventions

Continue with triple therapy DRUG

To continue with triple therapy

Triple therapy

Switch to DTG + 3TC DRUG

Switch to dolutegravir + lamivudine once daily

Switch to dual therapy A

Switch to DRV/cobicistat + 3TC DRUG

Switch to darunavir/cobicistat + lamivudine once daily

Switch to dual therapy B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1-infected patients ≥ 18 years of age.
• Starting date of antiretroviral treatment later than 01/01/2010
• Plasma HIV-1 RNA \<20 copies/ml for at least one year on triple therapy
• Antiretroviral treatment based on an integrase inhibitor plus two nucleos(t)ide analogs in the last 6 months.

You may not qualify if:

• Primary resistance to any of the drugs included in the study.
• Active opportunistic infection.
• Active hepatitis C and/or B virus co-infection.
• Cirrhosis, portal hypertension and/or hypersplenism of any etiology.
• Current or past malignancies 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.
• Concomitant use of drugs with potential major interactions with the prescribed drugs according to the respective full prescribing information.
• Estimated creatinine clearance \<50 ml/min

Sponsors & Collaborators

• Hospitales Universitarios Virgen del Rocío: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (1)

Virgen del Rocio University Hospital

Seville, 41013, Spain

Location

Related Publications (1)

• Munoz-Muela E, Trujillo-Rodriguez M, Serna-Gallego A, Saborido-Alconchel A, Ruiz-Mateos E, Lopez-Cortes LF, Gutierrez-Valencia A. HIV-1-specific T-cell responses and exhaustion profiles in people with HIV after switching to dual therapy vs. maintaining triple therapy based on integrase inhibitors. Biomed Pharmacother. 2023 Dec;168:115750. doi: 10.1016/j.biopha.2023.115750. Epub 2023 Oct 21.

  PMID: 37871555 DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Luis F Lopez-Cortes, PhD

  Virgen del Rocio University Hospital. Seville. Spain

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Researcher Andalusian Health System

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: February 27, 2018
• Study Start: June 1, 2017
• Primary Completion: September 15, 2020
• Study Completion: February 3, 2021
• Last Updated: August 30, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)