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

HIV Clinical Trial

— TRULIGHT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02302547
• Other study ID #: PHAO13-TP/TRULIGHT
• Status: Completed
• Phase: Phase 3
• Start date: December 2014
• Est. completion date: September 21, 2018

Study information

• Verified date: November 2018
• Source: University Hospital, Tours
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 224
• Est. completion date: September 21, 2018
• Est. primary completion date: August 23, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• triple therapy
Dosage treatment and usual prescription
• dual therapy
1 tablet (200mg/245mg) daily for 48 weeks

Locations

Country	Name	City	State
France	Unité des Maladies Infectieuses, CHU de CAEN	Caen
France	Service des Maladies Infectieuses, CHR Orléans La Source, ORLEANS CEDEX 2	CHR d'ORLEANS
France	Service d'Immunologie Clinique centre de Vaccination anti- VIH ANRS Hopital Henri- Mondor	Creteil
France	Service de Médecine Interne et Maladies Infectieuses, Groupe Hospitalier La Rochelle, Cedex 01	La Rochelle
France	Service de Pneumologie, centre Hospitalier Fontenoy, CH de CHARTRES	Le Coudray
France	CHU de NANCY	Nancy
France	Service des maladies Infectieuses et tropicales, CH GEORGES RENON	Niort
France	Centre de diagnostic et thérapeutique, Hopital Hotel Dieu	Paris
France	Hospital Tenon	Paris
France	Service des Maladies Infectieuses et tropicales, APHP SAINT LOUIS	Paris
France	Consultation Maladies Infectieuses, Chu de Poitiers, Cedex	Poitiers
France	Maladies Infectieuses, CHU de ROUEN	Rouen
France	Service de Médecine Interne, CH de SAINTONGE- BP 326	Saintes
France	Médecine Interne, Hôpital FOCH	Suresnes
France	Service Universitaire des Maladies Infectieuses et du Voyageur, CH DRON	Tourcoing
France	Service de Medecine Interne et Maladies Infectieuses, CHRU BRETONNEAU, TOURS CEDEX9	Tours

Sponsors (16)

Lead Sponsor	Collaborator
University Hospital, Tours	Central Hospital, Nancy, France, Central Hospital, NIORT, Centre Hospitalier de La Rochelle, HOSPITAL, CAEN, HOSPITAL, CHARTRES, HOSPITAL, FOCH, HOSPITAL, HENRI MONDOR, HOSPITAL, HOTEL DIEU, HOSPITAL, ORLEANS, HOSPITAL, SAINT LOUIS, HOSPITAL, SAINTES, Poitiers University Hospital, Tenon Hospital, Paris, Tourcoing Hospital, University Hospital, Rouen

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change from week 4 in Viral load at 48 weeks	percentage of patients having a viral load between 50 and 400 copies/ml between week 4 and week 48	between 4 weeks and 48 weeks
Secondary	CD 4 level in each arm	delta CD 4 measurement in each arm	48 weeks
Secondary	Change from day 0 in HIV - DNA at week 48	HIV DNA evolution between day 0 and week 48 in each arm	day 0 and 48 weeks
Secondary	RNA and DNA viral load (sub study)	RNA and DNA viral load in the genital tract (cervico-vaginal secretions or sperm): comparison between arms	Time Frame: Week 24 to Week 48