- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02302547
Trial to Evaluate the Interest of a Reductive Anti Retroviral Strategy Using Dual Therapy Inspite of Triple Therapy (TRULIGHT)
Randomized Clinical Trial to Evaluate the Interest of a Down-scaled Treatment Strategy Using Dual Therapy (Nucleoside Analogs) in HIV Infected Patients Already Being Treated Using Triple Therapy, Who Present With a Successful Virological Control and for Which the HIV Reservoir is Low to Moderate
In the early 2000s, the "TRILEGE©" study was realized to determine if the reductive anti retroviral strategy from an initial triple therapy (based on a protease inhibitor as the third agent) towards a dual therapy of nucleoside analogs (in particular the association of "zidovudine +lamivudine") for patients infected by HIV and stabilized for at least 3 months at a threshold value of 400 copies/ml, would allow to obtain a well-controlled plasmatic viral load, with an aim to reduce the long-term side effects of the treatment.
The afore mentioned study showed that the reductive anti retroviral strategy was a failure. No study has as yet to revaluate this strategy, in particular in the current context of antiretroviral treatments.
Indeed, modern nucleoside inhibitors (Kivexa®, Truvada®) have extended half-lives as well as a superior intrinsic power as compared to treatments proposed in the initial "TRILEGE©" study. Furthermore, the better quality of current triple therapy (as compared to that used 10 years ago) has lead to substantial viral reservoir reduction.
Currently, a small number of patients is being successfully treated in the long-term (viral load < 20 copies/ml) using nucleoside analog dual therapy. The particular characteristics of these patients have yet to be thoroughly investigated.
The patients concerned were all treated prematurely before ever passing below 200 lymphocytes T CD4/mm3. It occurred that all these patients presented a low viral reservoir as measured by HIV DNA quantification (< 2,7 log copies/106 PBMC).
Therefore, by targeting patients who have (1) a strong immune restoration, (2) a low HIV DNA value and (3) a very good observance, the investigators emit the hypothesis that, reductive anti retroviral strategy that would consist in changing from a conventional triple therapy towards a Nucleoside reverse-transcriptase inhibitors dual therapy, could allow for durable control of viral replication with the concomitant benefice of reduced antiretroviral side effects and cost.
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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CHR d'ORLEANS, France, 45067
- Service des Maladies Infectieuses, CHR Orléans La Source, ORLEANS CEDEX 2
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Caen, France, 14033
- Unité des Maladies Infectieuses, CHU de CAEN
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Creteil, France, 94010
- Service d'Immunologie Clinique centre de Vaccination anti- VIH ANRS Hopital Henri- Mondor
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La Rochelle, France, 17019
- Service de Médecine Interne et Maladies Infectieuses, Groupe Hospitalier La Rochelle, Cedex 01
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Le Coudray, France, 28630
- Service de Pneumologie, centre Hospitalier Fontenoy, CH de CHARTRES
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Nancy, France, 54035
- Chu de Nancy
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Niort, France, 79021
- Service des maladies Infectieuses et tropicales, CH GEORGES RENON
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Paris, France, 75475
- Service des Maladies Infectieuses et tropicales, APHP SAINT LOUIS
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Paris, France, 75970
- Hospital Tenon
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Paris, France, 94010
- Centre de diagnostic et thérapeutique, Hopital Hotel Dieu
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Poitiers, France, 86021
- Consultation Maladies Infectieuses, Chu de Poitiers, Cedex
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Rouen, France, 76031
- Maladies Infectieuses, CHU de ROUEN
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Saintes, France, 17108
- Service de Médecine Interne, CH de SAINTONGE- BP 326
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Suresnes, France, 92151
- Médecine Interne, Hôpital FOCH
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Tourcoing, France, 59200
- Service Universitaire des Maladies Infectieuses et du Voyageur, CH DRON
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Tours, France, 37044
- Service de Medecine Interne et Maladies Infectieuses, CHRU BRETONNEAU, TOURS CEDEX9
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- HIV-1 infected patient
- Initial TT ARV started above (or equal to) 150 / mm3 LT CD4, and 18 months prior to inclusion in the study
- Ongoing antiretroviral therapy combining tenofovir + emtricitabine + a 3rd agent (IP / r, IP, NNRTI, II, Inhibitors) with at least one undetectable viral load (CV <50 copies / mL) after introduction of the latter treatment.
- Patient in virological success: CV <50 copies / mL for at least 12 months, including visit to selection.
- Absence of previous therapeutic failure: no viral load ≥ 200 copies / mL (after 6 months of treatment) (Except in the case of a justified therapeutic interruption: travel, stock-out ...) and of obtaining success Virologic after introduction of treatment, without concept of genotypic resistance known to the ARVs used.
- Cellular DNA-HIV <2.7 log copies / 106 PBMC
- Zenith RNA-HIV <150,000 copies / ml (excluding viral load values during primary infection if it is documented)
- No genotypic resistance to currently used and known ARVs
- Patient who has given written informed consent
- Affiliate or beneficiary of a social security scheme
- Patient followed on an outpatient basis, age ≥ 18 years.
Exclusion Criteria:
- Non-compliant patient
- Subject is pregnant, or lactating, or of childbearing potential and without contraception
- Active opportunistic infections
- Major overweight (BMI ≥ 40)
- Severe renal pathology (creatinine clearance < 30ml/min)
- Cirrhosis or severe liver failure (factor V < 50%)
- Prognosis threatened within 6 months
- Circumstances that may impair judgment or understanding of the information given to the patient
- Malabsorption syndromes
The following laboratory criteria:
- Serum ASAT,ALAT > 5 x upper limit of normal (ULN)
- Thrombocytopenia with platelet count < 50.000/ml
- Anemia with hemoglobin < 8g/dl
- Polynuclear neutrophil count < 500/mm3
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: triple therapy
Tenofovir Disoproxil Fumarate (nucleotide reverse transcriptase inhibitor) + Emtricitabine (nucleoside reverse transcriptase inhibitor) + third agent (boosted protease inhibitor or unboosted protease inhibitor or integrase inhibitor or celsentri or non-nucleoside reverse transcriptase inhibitor).
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Dosage treatment and usual prescription
Other Names:
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Experimental: dual therapy
Truvada®"245mg":oral administration Tenofovir Disoproxil Fumarate (nucleotide reverse transcriptase inhibitor) + Emtricitabine (nucleoside reverse transcriptase inhibitor)
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1 tablet (200mg/245mg) daily for 48 weeks
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Viral Load at 48 weeks
Time Frame: 48 weeks
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Percentage of patient having a viral load < 50 copies/ml in each arm reductive anti retroviral strategy from an original backbone of 2 Nucleoside reverse transcriptase inhibitors (Tenofovir Disoproxil Fumarate+ Emtricitabine) coupled to a third agent, towards a therapeutic strategy containing the backbone therapy alone (Truvada®).
|
48 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from week 4 in Viral load at 48 weeks
Time Frame: between 4 weeks and 48 weeks
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percentage of patients having a viral load between 50 and 400 copies/ml between week 4 and week 48
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between 4 weeks and 48 weeks
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CD 4 level in each arm
Time Frame: 48 weeks
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delta CD 4 measurement in each arm
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48 weeks
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Change from day 0 in HIV - DNA at week 48
Time Frame: day 0 and 48 weeks
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HIV DNA evolution between day 0 and week 48 in each arm
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day 0 and 48 weeks
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RNA and DNA viral load (sub study)
Time Frame: Time Frame: Week 24 to Week 48
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RNA and DNA viral load in the genital tract (cervico-vaginal secretions or sperm): comparison between arms
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Time Frame: Week 24 to Week 48
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: LOUIS BERNARD, Pr, CHRU de Tours
- Principal Investigator: GWENAEL LE MOAL, Dr, Poitiers university hospital
- Principal Investigator: MARIAM RONCATO- SABERAN, Dr, CH de la Rochelle
- Principal Investigator: THIERRY PASDELOUPS, Dr, CH de SAINTES
- Principal Investigator: DAVID ZUCMAN, Dr, HOPITAL de FOCH
- Principal Investigator: RENAUD VERDON, Pr, University Hospital, Caen
- Principal Investigator: SEBASTIEN GALLIEN, Pr, CHU d'HENRI MONDOR
- Principal Investigator: JEAN - PAUL VIARD, Pr, CH d'HOTEL DIEU
- Principal Investigator: MARC LESTELLE, Dr, CH de Chartres
- Principal Investigator: JEAN - MICHEL MOLINA, Pr, CHU Saint Louis
- Principal Investigator: FAÏZA AJANA, Dr, CH de Tourcoing
- Principal Investigator: SIMON SUNDER, Dr, CH de Niort
- Principal Investigator: Gilles PIALOUX, Pr, Hospital Tenon
- Principal Investigator: Thierry MAY, Dr, Chu de Nancy
- Principal Investigator: Manuel ETIENNE, Dr, CHU de Rouen
Publications and helpful links
General Publications
- Hocqueloux L, Gubavu C, Prazuck T, De Dieuleveult B, Guinard J, Seve A, Mille C, Gardiennet E, Lopez P, Rouzioux C, Lefeuvre S, Avettand-Fenoel V. Genital Human Immunodeficiency Virus-1 RNA and DNA Shedding in Virologically Suppressed Individuals Switching From Triple- to Dual- or Monotherapy: Pooled Results From 2 Randomized, Controlled Trials. Clin Infect Dis. 2020 Apr 15;70(9):1973-1979. doi: 10.1093/cid/ciz511.
- Prazuck T, Verdon R, Le Moal G, Ajana F, Bernard L, Sunder S, Roncato-Saberan M, Ponscarme D, Etienne M, Viard JP, Pasdeloup T, Darasteanu I, Pialoux G, de la Blanchardiere A, Avettand-Fenoel V, Parienti JJ, Hocqueloux L; TRULIGHT Study Team. Tenofovir disoproxil fumarate and emtricitabine maintenance strategy in virologically controlled adults with low HIV-1 DNA: 48 week results from a randomized, open-label, non-inferiority trial. J Antimicrob Chemother. 2021 May 12;76(6):1564-1572. doi: 10.1093/jac/dkab038.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 CYP3A Inducers
- HIV Integrase Inhibitors
- Viral Protease Inhibitors
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2C9 Inhibitors
- HIV Fusion Inhibitors
- Viral Fusion Protein Inhibitors
- CCR5 Receptor Antagonists
- Cytochrome P-450 CYP2C19 Inhibitors
- Tenofovir
- Emtricitabine
- Cobicistat
- Nevirapine
- Raltegravir Potassium
- Ritonavir
- Lopinavir
- Indinavir
- Protease Inhibitors
- Maraviroc
- Tipranavir
- Enfuvirtide
- Reverse Transcriptase Inhibitors
- Darunavir
- Etravirine
- Atazanavir Sulfate
- Efavirenz
- Dolutegravir
- Rilpivirine
- Fosamprenavir
- Saquinavir
- Elvitegravir
- HIV Protease Inhibitors
- Integrase Inhibitors
Other Study ID Numbers
- PHAO13-TP/TRULIGHT
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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