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

NCT ID: NCT02302547

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

224 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-12-31

Study Completion Date

2018-09-21

Brief Summary

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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.

Detailed Description

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Conditions

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HIV

Keywords

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truvada® HIV-DNA dual therapy NRTI virological control

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type ACTIVE_COMPARATOR

triple therapy

Intervention Type DRUG

Dosage treatment and usual prescription

dual therapy

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

Group Type EXPERIMENTAL

dual therapy

Intervention Type DRUG

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

Interventions

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triple therapy

Dosage treatment and usual prescription

Intervention Type DRUG

dual therapy

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

Intervention Type DRUG

Other Intervention Names

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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 Truvada®

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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HOSPITAL, ORLEANS

UNKNOWN

Sponsor Role collaborator

Poitiers University Hospital

OTHER

Sponsor Role collaborator

Centre Hospitalier de La Rochelle

OTHER

Sponsor Role collaborator

HOSPITAL, SAINTES

UNKNOWN

Sponsor Role collaborator

HOSPITAL, FOCH

UNKNOWN

Sponsor Role collaborator

HOSPITAL, CAEN

UNKNOWN

Sponsor Role collaborator

Henri Mondor University Hospital

OTHER

Sponsor Role collaborator

HOSPITAL, HOTEL DIEU

UNKNOWN

Sponsor Role collaborator

HOSPITAL, CHARTRES

UNKNOWN

Sponsor Role collaborator

HOSPITAL, SAINT LOUIS

UNKNOWN

Sponsor Role collaborator

Tourcoing Hospital

OTHER

Sponsor Role collaborator

Central Hospital, NIORT

UNKNOWN

Sponsor Role collaborator

Tenon Hospital, Paris

OTHER

Sponsor Role collaborator

Central Hospital, Nancy, France

OTHER

Sponsor Role collaborator

University Hospital, Rouen

OTHER

Sponsor Role collaborator

University Hospital, Tours

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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LOUIS BERNARD, Pr

Role: PRINCIPAL_INVESTIGATOR

CHRU de TOURS

GWENAEL LE MOAL, Dr

Role: PRINCIPAL_INVESTIGATOR

Poitiers University Hospital

MARIAM RONCATO- SABERAN, Dr

Role: PRINCIPAL_INVESTIGATOR

CH de LA ROCHELLE

THIERRY PASDELOUPS, Dr

Role: PRINCIPAL_INVESTIGATOR

CH de SAINTES

DAVID ZUCMAN, Dr

Role: PRINCIPAL_INVESTIGATOR

HOPITAL de FOCH

RENAUD VERDON, Pr

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Caen

SEBASTIEN GALLIEN, Pr

Role: PRINCIPAL_INVESTIGATOR

CHU d'HENRI MONDOR

JEAN - PAUL VIARD, Pr

Role: PRINCIPAL_INVESTIGATOR

CH d'HOTEL DIEU

MARC LESTELLE, Dr

Role: PRINCIPAL_INVESTIGATOR

CH de CHARTRES

JEAN - MICHEL MOLINA, Pr

Role: PRINCIPAL_INVESTIGATOR

CHU SAINT LOUIS

FAÏZA AJANA, Dr

Role: PRINCIPAL_INVESTIGATOR

CH de TOURCOING

SIMON SUNDER, Dr

Role: PRINCIPAL_INVESTIGATOR

CH de NIORT

Gilles PIALOUX, Pr

Role: PRINCIPAL_INVESTIGATOR

HOSPITAL TENON

Thierry MAY, Dr

Role: PRINCIPAL_INVESTIGATOR

Central Hospital, Nancy, France

Manuel ETIENNE, Dr

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Rouen

Locations

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Unité des Maladies Infectieuses, CHU de CAEN

Caen, , France

Site Status

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

CHR d'ORLEANS, , France

Site Status

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

Créteil, , France

Site Status

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

La Rochelle, , France

Site Status

Service de Pneumologie, centre Hospitalier Fontenoy, CH de CHARTRES

Le Coudray, , France

Site Status

CHU de NANCY

Nancy, , France

Site Status

Service des maladies Infectieuses et tropicales, CH GEORGES RENON

Niort, , France

Site Status

Service des Maladies Infectieuses et tropicales, APHP SAINT LOUIS

Paris, , France

Site Status

Hospital Tenon

Paris, , France

Site Status

Centre de diagnostic et thérapeutique, Hopital Hotel Dieu

Paris, , France

Site Status

Consultation Maladies Infectieuses, Chu de Poitiers, Cedex

Poitiers, , France

Site Status

Maladies Infectieuses, CHU de ROUEN

Rouen, , France

Site Status

Service de Médecine Interne, CH de SAINTONGE- BP 326

Saintes, , France

Site Status

Médecine Interne, Hôpital FOCH

Suresnes, , France

Site Status

Service Universitaire des Maladies Infectieuses et du Voyageur, CH DRON

Tourcoing, , France

Site Status

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

Tours, , France

Site Status

Countries

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France

References

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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.

Reference Type BACKGROUND
PMID: 33724373 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31350995 (View on PubMed)

Other Identifiers

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PHAO13-TP/TRULIGHT

Identifier Type: -

Identifier Source: org_study_id