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)

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.

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.

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.