Clinical trial NCT02527096: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
Keywords: dolutegravir(Tivicay®)
lamivudine(Epivir®)
HIV-1
efficacy
safety
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: ViiV Healthcare
First posted: 2015-08-18
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Virological success without any intercurrent event leading to interrupt the strategy of the trial (analysis)
timeFrame: from week 8 to week 56 (± 4 weeks)
Secondary outcomes:
measure: Evolution of CD4 and CD8 lymphocytes count (analysis)
timeFrame: from week 8 to week 32 and week 56
measure: Percentage of participants who discontinued the strategy of the trial for toxicity or with adverse event of grade 3 or 4 (analysis)
timeFrame: week 56
measure: Profile of resistance mutations in plasma in case of virological failure
timeFrame: week 56
measure: Percentage of participants with plasma HIV RNA < 1 cp/mL
timeFrame: Day 0, week 8, week 32 and week 56
measure: Influence of total DNA on the occurrence of virological failure or blip
timeFrame: from Day 0 to week 56
measure: Measure of concentrations of dolutegravir(Tivicay®) and lamivudine(Epivir®) in case of virological failure or with a blip
timeFrame: week 56
measure: Measure of adherence to treatment (self-reported)
timeFrame: Day 0, week 4, week 8, week 32 and week 56
measure: Measure of quality of life (self-reported)
timeFrame: Day 0, week 8 and week 56
measure: Comparison of Medico-economic substudy (analysis)
timeFrame: week 56
measure: Sperm substudy measure of concentration
timeFrame: Week 8 and week 32
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bordeaux
country: France
facility: Hôpital Saint-André
city: Clermont-Ferrand
country: France
facility: Hôpital Gabriel Montpied
city: Dijon
country: France
facility: Hôpital du Bocage
city: Fort de France
country: France
facility: Hôpital Pierre Zobda-Quitman
city: Le Kremelin Bicêtre
country: France
facility: Hôpial Bicêtre
city: Montpellier
country: France
facility: Hôpital Gui de Chaudiac
city: Nantes
country: France
facility: Hôpital de l'Hotel Dieu
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière
city: Paris
country: France
facility: Hôpital Necker
city: Paris
country: France
facility: Hôpital Bichat
city: Perpignan
country: France
facility: Centre hospitalier de Pernignan
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Toulouse
country: France
facility: Hôpital Purpan
city: Tourcoing
country: France
facility: Hôpital Gustave Dron
city: Tours
country: France
facility: Hôpital Bretonneau
Study officials:
affiliation: Service des Maladies Infectieuses, Hôpital Bichat-Claude Bernard, Paris
name: Véronique JOLY, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service des Maladies Infectieuses, Hôpital Bichat-Claude Bernard
name: Yazdan YAZDANPANAH, MD
role: STUDY_CHAIR
affiliation: Institut de Médecine et Epidémiologie Appliquée (IMEA), Paris
name: Roland LANDMAN, MD
role: STUDY_DIRECTOR
References: