Trial to Evaluate the Interest of a Reductive Anti Retroviral Strategy Using Dual Therapy Inspite of Triple Therapy

NCT02302547 | Completed Phase 3 DMC

• 1 other identifier: PHAO13-TP/TRULIGHT
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

HIV

Keywords

HIV-DNA; dual therapy; NRTI; virological control; truvada®

Outcome Measures

Primary Outcomes (1)

• Viral Load at 48 weeks

  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

Secondary Outcomes (4)

• Change from week 4 in Viral load at 48 weeks

  between 4 weeks and 48 weeks

• CD 4 level in each arm

  48 weeks

• Change from day 0 in HIV - DNA at week 48

  day 0 and 48 weeks

• RNA and DNA viral load (sub study)

  Time Frame: Week 24 to Week 48

Study Arms (2)

triple therapy

ACTIVE COMPARATOR

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).

Drug: triple therapy

dual therapy

EXPERIMENTAL

Truvada®"245mg":oral administration Tenofovir Disoproxil Fumarate (nucleotide reverse transcriptase inhibitor) + Emtricitabine (nucleoside reverse transcriptase inhibitor)

Drug: dual therapy

Interventions

triple therapy DRUG

Dosage treatment and usual prescription

Also known as: Tenofovir+Emtricitabine+Third agent (Including a non nucleoside reverse transcriptase inhibitor: efavirenz or nevirapine or etravirine or rilpivirine, Tenofovir+Emtricitabine+Third agent (Including a ritonavir-boosted protease inhibitor : saquinavir or indinavir or fosamprenavir or tipranavir or darunavir or atazanavir or lopinavir, Tenofovir+Emtricitabine+Third agent (Including an unboosted protease inhibitor: atazanavir or indinavir, Tenofovir+Emtricitabine+Third agent (Including an integrase inhibitor raltegravir or dolutegravir or cobicistat-boosted elvitegravir, Tenofovir+Emtricitabine+Third agent (Including a fusion inhibitor: enfuvirtide or a CCR5 antagonist :maraviroc

triple therapy

dual therapy DRUG

1 tablet (200mg/245mg) daily for 48 weeks

Also known as: Truvada®

dual therapy

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 patient
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Tours: lead
• HOSPITAL, ORLEANS: collaborator
• Poitiers University Hospital: collaborator
• Centre Hospitalier de La Rochelle: collaborator
• HOSPITAL, SAINTES: collaborator
• HOSPITAL, FOCH: collaborator
• HOSPITAL, CAEN: collaborator
• Henri Mondor University Hospital: collaborator
• HOSPITAL, HOTEL DIEU: collaborator
• HOSPITAL, CHARTRES: collaborator
• HOSPITAL, SAINT LOUIS: collaborator
• Tourcoing Hospital: collaborator
• Central Hospital, NIORT: collaborator
• Tenon Hospital, Paris: collaborator
• Central Hospital, Nancy, France: collaborator
• University Hospital, Rouen: collaborator

Study Sites (16)

Unité des Maladies Infectieuses, CHU de CAEN

Caen, 14033, France

Location

Service des Maladies Infectieuses, CHR Orléans La Source, ORLEANS CEDEX 2

CHR d'ORLEANS, 45067, France

Location

Service d'Immunologie Clinique centre de Vaccination anti- VIH ANRS Hopital Henri- Mondor

Créteil, 94010, France

Location

Service de Médecine Interne et Maladies Infectieuses, Groupe Hospitalier La Rochelle, Cedex 01

La Rochelle, 17019, France

Location

Service de Pneumologie, centre Hospitalier Fontenoy, CH de CHARTRES

Le Coudray, 28630, France

Location

CHU de NANCY

Nancy, 54035, France

Location

Service des maladies Infectieuses et tropicales, CH GEORGES RENON

Niort, 79021, France

Location

Service des Maladies Infectieuses et tropicales, APHP SAINT LOUIS

Paris, 75475, France

Location

Hospital Tenon

Paris, 75970, France

Location

Centre de diagnostic et thérapeutique, Hopital Hotel Dieu

Paris, 94010, France

Location

Consultation Maladies Infectieuses, Chu de Poitiers, Cedex

Poitiers, 86021, France

Location

Maladies Infectieuses, CHU de ROUEN

Rouen, 76031, France

Location

Service de Médecine Interne, CH de SAINTONGE- BP 326

Saintes, 17108, France

Location

Médecine Interne, Hôpital FOCH

Suresnes, 92151, France

Location

Service Universitaire des Maladies Infectieuses et du Voyageur, CH DRON

Tourcoing, 59200, France

Location

Service de Medecine Interne et Maladies Infectieuses, CHRU BRETONNEAU, TOURS CEDEX9

Tours, 37044, France

Location

Related Publications (2)

• 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.

  PMID: 33724373 BACKGROUND

• 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.

  PMID: 31350995 DERIVED

MeSH Terms

Interventions

Nevirapine; etravirine; Rilpivirine; Indinavir; fosamprenavir; tipranavir; Darunavir; Atazanavir Sulfate; Lopinavir; dolutegravir; Dual Anti-Platelet Therapy; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitriles; Organic Chemicals; Pyrimidines; Sulfonamides; Amides; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Pyrimidinones; Drug Therapy, Combination; Drug Therapy; Therapeutics; Tenofovir; Organophosphonates; Organophosphorus Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• 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

  Central Hospital, Nancy, France

  PRINCIPAL INVESTIGATOR

• Manuel ETIENNE, Dr

  University Hospital, Rouen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2014
• First Posted: November 27, 2014
• Study Start: December 1, 2014
• Primary Completion: August 23, 2017
• Study Completion: September 21, 2018
• Last Updated: December 26, 2025

Record last verified: 2018-11

Locations

FR (16)