Clinical trial NCT02159599: Study to Evaluate Darunavir/Ritonavir + Lamivudine Versus Continuing With Darunavir/Ritonavir + Tenofovir/Emtricitabine or Abacavir/Lamivudine in HIV Infected Subject
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infection
Lead sponsor: Fundacion SEIMC-GESIDA
Sponsor class: OTHER
Collaborators: name: Janssen, LP
First posted: 2014-06-10
Enrollment: 249
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients with undetectable viral load
timeFrame: week 48
Secondary outcomes:
measure: Proportion of patients with undetectable viral load
timeFrame: Week 24
measure: Proportion of patients with viral load < 200 copies/ml
timeFrame: week 48
measure: Proportion of patients who present viral load ≥ 50 copies /ml one time
timeFrame: From basal visit until week 48 visit
measure: Proportion of patients who present viral load ≥ 50 copies /ml more tan two times
timeFrame: From basal visit until week 48 visit
measure: Proportion of patients who maintained viral load < 50 copies/ml in all determinations
timeFrame: week 48
measure: Median of change cells CD4/µl count from basal to week 48
timeFrame: week 48
measure: Median of change in triglycerides , LDL-cholesterol, HDL-cholesterol and total cholesterol from basal to week 48
timeFrame: week 48
measure: Change in renal function
timeFrame: week 48
measure: Change in proportion of patients with renal tubular dysfunction
timeFrame: week 48
Other outcomes:
measure: Proportion of genotypic resistance mutations
timeFrame: Week 48
measure: Change in proportion of genotypic resistance mutations
timeFrame: week 48
Locations:
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitario Vall D'Hebron
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Huelva
country: Spain
facility: Complejo Hospitalario de Huelva
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Alcorcón
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital universitario Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Príncipe de Asturias
city: Mataró
country: Spain
facility: Hospital de Mataró
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: San Sebastián
country: Spain
facility: Hospital Universitario Donostia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Hospital Universitario La Paz
name: Jose R Arribas, MD
role: STUDY_DIRECTOR
affiliation: Hospital Universitario 12 de Octubre
name: Federico Pulido, MD
role: STUDY_DIRECTOR
affiliation: Hospital Vall d'Hebron
name: Esteban Ribera, MD
role: STUDY_DIRECTOR
References:
citation: 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.