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)

ANRS, Emerging Infectious Diseases

Status and phase

Completed

Phase 2

Conditions

HIV-1 Infection

Treatments

Drug: lamivudine (Epivir®) - Phase 2

Drug: dolutegravir (Tivicay®) - Phase 1

Drug: dolutegravir (Tivicay®) - Phase 2

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02527096

2015-001492-44 (EudraCT Number)

ANRS 167 Lamidol

Details and patient eligibility

About

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.

Full 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.

Enrollment

110 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.