A Trial Evaluating Maintenance Therapy With Lamivudine (Epivir®) and Dolutegravir (Tivicay®) in Human Immunodeficiency Virus 1 (HIV-1) Infected Patients Virologically Suppressed With Triple Highly Active Antiretroviral Therapy (HAART) (ANRS 167 Lamidol)

August 18, 2017 updated by: ANRS, Emerging Infectious Diseases

A Pilot Trial Evaluating Maintenance Therapy With Lamivudine(Epivir®) and Dolutegravir(Tivicay®) in Human Immunodeficiency Virus 1 (HIV-1) Infected Patients Virologically Suppressed With Triple HAART - ANRS 167 Lamidol

The principal objective is to evaluate the antiviral efficacy of 48 weeks treatment with the two-drugs combination dolutegravir(Tivicay®) and lamivudine(TEpivir®) in HIV-1 infected patients virologically suppressed with triple HAART.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Secondary objectives:

The following parameters will be evaluated :

  • Evolution of CD4 cells and CD8 cells
  • Tolerance to treatment
  • Emergence of resistance mutations at time of virological failure
  • HIV viral load measured with ultrasensitive assay (threshold 1 copy/mL) at Day 0, Week 8, Week 32 and Week 56
  • Influence of total DNA at Day 0 on the occurrence of virological failure or blip
  • Plasma levels of dolutegravir(Tivicay®) and lamivudine in participants with virological failure
  • Adherence to treatment
  • Quality of life
  • Medico-economic aspects
  • Dolutegravir(Tivicay®) and Nucleosidic Reverse Transcriptase Inhibitors (NRTIs) levels, and HIV viral load in semen in a subgroup of 20 participants.

Methodology:

Pilot trial, multicentric, national, prospective, no randomized and no comparative.

Study Type

Interventional

Enrollment (Actual)

110

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Bobigny, France, 93009
        • Hopital Avicenne
      • Bordeaux, France, 33000
        • Hôpital Saint-André
      • Clermont-Ferrand, France, 63003
        • Hopital Gabriel Montpied
      • Dijon, France, 21079
        • Hôpital du Bocage
      • Fort de France, France, 97261
        • Hôpital Pierre Zobda-Quitman
      • Le Kremelin Bicêtre, France, 94270
        • Hôpial Bicêtre
      • Montpellier, France, 34295
        • Hôpital Gui de Chaudiac
      • Nantes, France, 44093
        • Hôpital de l'Hôtel Dieu
      • Paris, France, 75012
        • Hôpital Saint-Antoine
      • Paris, France, 75010
        • Hôpital Saint-Louis
      • Paris, France, 75015
        • Hopital Necker
      • Paris, France, 75013
        • Hôpital Pitié-Salpétrière
      • Paris, France, 75018
        • Hôpital Bichat
      • Perpignan, France, 66046
        • Centre hospitalier de Pernignan
      • Rennes, France, 35033
        • Hôpital Pontchaillou
      • Toulouse, France, 31059
        • Hopital Purpan
      • Tourcoing, France, 59208
        • Hôpital Gustave Dron
      • Tours, France, 37044
        • Hopital Bretonneau

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • HIV-1 infected patient
  • Age ≥ 18 years
  • CD4 cell count nadir > 200/mm3

  • Genotype on pre-HAART interpreted with the last version of the ANRS AC11 resistance group's algorithm which presents:

    • no major mutation on protease among: D30N, V32I, M46I/L, I47A/V, G48V, I50L/V, 154M/L, L76V, V82A/F/T/S, I84V, N88D/S, L90M,- no mutation on RT (except the mutation A98S if the patient is not infected by the virus subtype C),
    • no mutation on integrase (if the genotype is available),
  • First-line treatment with suppressive triple HAART (2 NRTI + either 1 PI/r, 1 NNRTI or 1 INI). The initial treatment may have changed a maximum of two times but only once for toxicity (changes such Epivir / Ziagen to Kivexa, are not considered as a change of treatment). However, treatment has to be unchanged in the last 6 months
  • Plasma HIV RNA ≤ 50 copies/mL for ≥ 2 years with at least 2 viral load determinations per year. Blips (HIV viral load between 50 and 200 copies/mL but ≤ 50 copies/mL on control sample) are allowed except in the last 6 months. The total number of blips must not exceed 3 in the last 2 years
  • Negative Hepatitis Bs Antigen
  • Effective contraception for women of childbearing potential
  • Informed consent form signed by patient and investigator
  • Patient enrolled in or a beneficiary of a Social Security programme (State Medical Aid ("Aide Médicale d'Etat" AME in France) is not a Social Security programme)

Exclusion Criteria:

  • HIV-2 infection
  • Positive HBc Ac isolated
  • Hepatitis B Virus (HBV) co-infected patients (positive Hepatitis Bs Ag at inclusion)
  • Chronic hepatitis C currently treated or needing therapy in the next 12 months
  • History of HIV-associated neurocognitive disorders
  • Current pregnancy or breastfeeding
  • No effective contraception for the women of childbearing
  • Previous treatment with chemotherapy (except bleomycin on Kaposi disease's treatment) or immunotherapy
  • Grade > 2 abnormality for usual biological parameters (liver function tests, blood cell count)
  • ALT(Alanine Aminotransferase) ≥ 5 x upper limit of normal value (ULN) or AST (Aspartate Aminotransferase) ≥ 3 x ULN and bilirubinemia ≥ 1.5 x ULN (with 35% direct bilirubinemia)
  • Unstable liver disease (ascitis, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices or persistent jaundice)
  • Known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • Creatininemia clearance below 50 mL/min (Cockroft-Gault method)
  • History or presence of allergy to the trial drugs or their components
  • Severe hepatic insufficiency (Child Pugh Class C)
  • Patients participating in another clinical trial including an exclusion period that is still in force during the screening phase
  • Patients under "sauvegarde de justice" (judicial protection due to temporarily and slightly diminished mental or physical faculties) or under legal guardianship.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: dolutegravir(Tivicay®) and lamivudine(Epivir®)
Drug: dolutegravir (Tivicay®) - Phase 1
• Phase 1 (8 weeks) : switch of the third agent with dolutegravir(Tivicay®) 50 mg once a day.
Drug: lamivudine (Epivir®) - Phase 2
• Phase 2 (48 weeks): combination with lamivudine (Epivir®) 300 mg once a day + dolutegravir (Tivicay®) 50 mg once a day. Only participants with plasma HIV RNA ≤ 50 cp/mL at Week 8 will continue on phase 2.
Drug: dolutegravir (Tivicay®) - Phase 2
• Phase 2 (48 weeks): combination with lamivudine (Epivir®) 300 mg once a day + dolutegravir (Tivicay®) 50 mg once a day. Only participants with plasma HIV RNA ≤ 50 cp/mL at Week 8 will continue on phase 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Virological success without any intercurrent event leading to interrupt the strategy of the trial (analysis)
Time Frame: from week 8 to week 56 (± 4 weeks)
Virological failure is defined by plasma HIV RNA > 50 cp/mL on 2 following samples at 2 to 4 weeks apart.
from week 8 to week 56 (± 4 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evolution of CD4 and CD8 lymphocytes count (analysis)
Time Frame: from week 8 to week 32 and week 56
Evaluation was calculated as the CD4 count at the corresponding week minus the baseline CD4 count
from week 8 to week 32 and week 56
Percentage of participants who discontinued the strategy of the trial for toxicity or with adverse event of grade 3 or 4 (analysis)
Time Frame: week 56
week 56
Profile of resistance mutations in plasma in case of virological failure
Time Frame: week 56
week 56
Percentage of participants with plasma HIV RNA < 1 cp/mL
Time Frame: Day 0, week 8, week 32 and week 56
Day 0, week 8, week 32 and week 56
Influence of total DNA on the occurrence of virological failure or blip
Time Frame: from Day 0 to week 56
Influence of total DNA at Day 0 on the occurrence of virological failure or blip
from Day 0 to week 56
Measure of concentrations of dolutegravir(Tivicay®) and lamivudine(Epivir®) in case of virological failure or with a blip
Time Frame: week 56
week 56
Measure of adherence to treatment (self-reported)
Time Frame: Day 0, week 4, week 8, week 32 and week 56
Day 0, week 4, week 8, week 32 and week 56
Measure of quality of life (self-reported)
Time Frame: Day 0, week 8 and week 56
Day 0, week 8 and week 56
Comparison of Medico-economic substudy (analysis)
Time Frame: week 56
Evaluation of medico-economic aspects. Evaluate the direct medical cost related to dolutegravir and lamivudine versus the cost of the previous treatment.
week 56
Sperm substudy measure of concentration
Time Frame: Week 8 and week 32
Measure of concentrations of dolutegravir and NRTI, and HIV RNA in semen at Week 8 and Week 32 in a subgroup of 20 participants
Week 8 and week 32

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ANRS, Emerging Infectious Diseases

Collaborators

ViiV Healthcare

Investigators

  • Principal Investigator: Véronique JOLY, MD, Service des Maladies Infectieuses, Hôpital Bichat-Claude Bernard, Paris
  • Study Chair: Yazdan YAZDANPANAH, MD, Service des Maladies Infectieuses, Hôpital Bichat-Claude Bernard
  • Study Director: Roland LANDMAN, MD, Institut de Médecine et Epidémiologie Appliquée (IMEA), Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 17, 2015

Primary Completion (Actual)

March 1, 2017

Study Completion (Actual)

March 1, 2017

Study Registration Dates

First Submitted

August 6, 2015

First Submitted That Met QC Criteria

August 17, 2015

First Posted (Estimate)

August 18, 2015

Study Record Updates

Last Update Posted (Actual)

August 22, 2017

Last Update Submitted That Met QC Criteria

August 18, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANRS 167 Lamidol
  • 2015-001492-44 (EudraCT Number)

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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