Study to Evaluate Darunavir/Ritonavir + Lamivudine Versus Continuing With Darunavir/Ritonavir + Tenofovir/Emtricitabine or Abacavir/Lamivudine in HIV Infected Subject (DUAL)

An Open Label Randomized Clinical Trial, to Evaluate the Treatment With Darunavir/Ritonavir + Lamivudine Once Daily Versus Continuing With Darunavir/Ritonavir Once Daily + Tenofovir/Emtricitabine or Abacavir/Lamivudine in HIV Infected Subject With Suppressed Plasma Viremia

This is an open label randomized clinial trial to evaluate the treatment with darunavir/ritonavir (800mg/100mg) plus lamivudine (300 mg) once daily versus continuing with darunavir/ritonavir (800mg/100mg) once daily plus tenofovir/emtricitabine (300mg/200mg) or abacavir/lamivudine (600mg/300mg) in HIV infected subject with suppressed plasma viremia.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Drug: Darunavir/Ritonavir; Drug: Emtricitabine/tenofovir or abacavir/lamivudine; Drug: Lamivudine

• Study Type: Interventional
• Enrollment (Actual): 249
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Alicante, Spain
    • Hospital General Universitario de Alicante
  • Badalona, Spain
    • Hospital Universitario Germans Trias i Pujol
  • Barcelona, Spain
    • Hospital del Mar
  • Barcelona, Spain
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain
    • Hospital Clínic
  • Barcelona, Spain
    • Hospital Universitario Vall d'Hebrón
  • Córdoba, Spain
    • Hospital Universitario Reina Sofía
  • Granada, Spain
    • Hospital Universitario Virgen de las Nieves
  • Huelva, Spain
    • Complejo Hospitalario de Huelva
  • Madrid, Spain
    • Hospital 12 de Octubre
  • Madrid, Spain
    • Hospital Universitario Clinico San Carlos
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Hospital Universitario Gregorio Marañon
  • Madrid, Spain
    • Hospital Universitario Infanta Leonor
  • Madrid, Spain
    • Hospital Universitario Fundación Alcorcón
  • Madrid, Spain
    • Hospital Universitario Príncipe de Asturias
  • Mataró, Spain
    • Hospital de Mataro
  • Málaga, Spain
    • Hospital Universitario Virgen de la Victoria
  • San Sebastián, Spain
    • Hospital Universitario Donostia
  • Zaragoza, Spain
    • Hospital Universitario Miguel Servet
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain
      • Hospital Universitario de Bellvitge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Acceptance to participate in the study, signing the informed consent document before conducting any study procedures.
2. Patient with HIV infection older than 18 years.
3. Treatment with darunavir/ritonavir once a day and tenofovir/emtricitabine or abacavir/lamivudine during at least 4 weeks at the moment of the screening
4. Plasma HIV RNA levels below 50 copies / ml for at least 6 months (two separate measurements at least 6 months with viremia <50 copies / ml between both).
5. HbsAg negative

Exclusion Criteria:

1. Pregnant or breastfeeding woman
2. Evidence of Lamivudine resistance (any previous genotype with mutation M184V/I or K65R) and/or to darunavir (population genotype show any of the following mutations: V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, T74P, L76V, I84V, L89V).

3. History of virology failure (two consecutive viral loads above 200 copies/ml) while the patient was receiving a regimen with lamivudine or emtricitabine, with the following exceptions:

   • Do not consider an exclusion criterion if the genotype performed at the time of failure does not demonstrate resistance to lamivudine and darunavir (see criteria 2).
   • Do not consider an exclusion criteria in the absence of genotype if after the episode turns to maintain a viral load <50 copies / ml with a treatment composed of lamivudine or emtricitabine + a nucleoside + a non-nucleoside.

4. History of abandonment of treatment including lamivudine or emtricitabine, with the following exception:

   - Viral load prior to abandonment was <50 copies / ml and subsequent reintroduction of the same treatment or another treatment consisting of lamivudine or emtricitabine + a nucleoside + a non-nucleoside returns to maintain viral load below 50 copies / ml .

5. Previous treatment with bitherapy or monotherapy with lamivudine or emtricitabine
6. Previous treatment with bitherapy or monotherapy with a regimen with a protease inhibitor that is terminated by viral rebound, when the absence of a genotypic resistance test available after viral rebound allow discard the resistance mutations either drug used.
7. The use of concomitant medication not permitted
8. Presence of active acute infection, including opportunist infection that a judge of investigator that can difficult the participation in the trial
9. Any laboratory results of the following: hemoglobin<8,0 g/dl; neutrophils <750 cells/µl; platelets <50.000 cell/µl; creatinine ≥ 1,5 ULN (upper limit of normal)
10. Any clinical or analytic event that, in the investigator judgment, condition the patient safety

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Darunavir/Ritonavir + 2 nucleos(t)idos; Darunavir/Ritonavir ( (800mg/100mg) + Tenofovir/emtricitabine (300mg/200mg) or Abacavir/lamivudine (600 mg/300mg)	Drug: Darunavir/Ritonavir; Darunavir/ritonavir (800/100 mg): QD (quaque die ); Other Names: Prezista/Norvir; Drug: Emtricitabine/tenofovir or abacavir/lamivudine; Emtricitabine/tenofovir (300/200 mg) or abacavir/lamivudine (600/300 mg): QD; Other Names: Truvada or Kivexa
Experimental: Darunavir/ritonavir + Lamivudine; Darunavir/Ritonavir (800mg7100mg) + lamivudine (300mg)	Drug: Darunavir/Ritonavir; Darunavir/ritonavir (800/100 mg): QD (quaque die ); Other Names: Prezista/Norvir; Drug: Lamivudine; Lamivudine (300mg) : QD; Other Names: Epivir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with undetectable viral load	Undetectable viral load <50 copies/ml according to the FDA snapshot algorithm	week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with undetectable viral load	Undetectable viral load < 50 copies/ml according to the FDA snapshot algorithm	Week 24
Proportion of patients with viral load < 200 copies/ml	Proportion of patients with viral load < 200 copies/ml according to FDA snapshot algorithm	week 48
Proportion of patients who present viral load ≥ 50 copies /ml one time	Viral load ≥ 50 copies/ml	From basal visit until week 48 visit
Proportion of patients who present viral load ≥ 50 copies /ml more tan two times	Viral load ≥ 50 copies /ml	From basal visit until week 48 visit
Proportion of patients who maintained viral load < 50 copies/ml in all determinations	Viral load < 50 copies/ml	week 48
Median of change cells CD4/µl count from basal to week 48	CD4/µl	week 48
Median of change in triglycerides , LDL-cholesterol, HDL-cholesterol and total cholesterol from basal to week 48		week 48
Change in renal function	Change in glomerular filtration	week 48
Change in proportion of patients with renal tubular dysfunction		week 48

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of genotypic resistance mutations	Mutations in patients viral failure	Week 48
Change in proportion of genotypic resistance mutations		week 48

Collaborators and Investigators

• Sponsor: Fundacion SEIMC-GESIDA
• Collaborators: Janssen, LP
• Investigators: Study Director: Jose R Arribas, MD, Hospital Universitario La Paz; Study Director: Federico Pulido, MD, Hospital Universitario 12 de octubre; Study Director: Esteban Ribera, MD, Hospital Vall d'Hebron

Publications and helpful links

General Publications

• Pulido F, Ribera E, Lagarde M, Perez-Valero I, Palacios R, Iribarren JA, Payeras A, Domingo P, Sanz J, Cervero M, Curran A, Rodriguez-Gomez FJ, Tellez MJ, Ryan P, Barrufet P, Knobel H, Rivero A, Alejos B, Yllescas M, Arribas JR; DUAL-GESIDA-8014-RIS-EST45 Study Group. Dual Therapy With Darunavir and Ritonavir Plus Lamivudine vs Triple Therapy With Darunavir and Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine or Abacavir and Lamivudine for Maintenance of Human Immunodeficiency Virus Type 1 Viral Suppression: Randomized, Open-Label, Noninferiority DUAL-GESIDA 8014-RIS-EST45 Trial. Clin Infect Dis. 2017 Nov 29;65(12):2112-2118. doi: 10.1093/cid/cix734.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: May 27, 2014
• First Submitted That Met QC Criteria: June 6, 2014
• First Posted (Estimate): June 10, 2014

Study Record Updates

• Last Update Posted (Actual): February 14, 2017
• Last Update Submitted That Met QC Criteria: February 13, 2017
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Ritonavir; Lamivudine; Darunavir; Abacavir
• Other Study ID Numbers: GESIDA 8014; 2014-000515-14 (EudraCT Number)