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)

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02527096
• Other study ID #: ANRS 167 Lamidol
• Secondary ID: 2015-001492-44
• Status: Completed
• Phase: Phase 2
• First received: August 6, 2015
• Last updated: August 18, 2017
• Start date: September 17, 2015
• Est. completion date: March 2017

Study information

• Verified date: August 2017
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: March 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• HIV-1 Infection
• Immunologic Deficiency Syndromes

Intervention

Drug:
• dolutegravir (Tivicay®) - Phase 1
• Phase 1 (8 weeks) : switch of the third agent with dolutegravir(Tivicay®) 50 mg once a day.
• 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.
• 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.

Locations

Country	Name	City	State
France	Hôpital Avicenne	Bobigny
France	Hôpital Saint-André	Bordeaux
France	Hôpital Gabriel Montpied	Clermont-Ferrand
France	Hôpital du Bocage	Dijon
France	Hôpital Pierre Zobda-Quitman	Fort de France
France	Hôpial Bicêtre	Le Kremelin Bicêtre
France	Hôpital Gui de Chaudiac	Montpellier
France	Hôpital de l'Hotel Dieu	Nantes
France	Hôpital Bichat	Paris
France	Hôpital Necker	Paris
France	Hôpital Pitié-Salpêtrière	Paris
France	Hôpital Saint-Antoine	Paris
France	Hôpital Saint-Louis	Paris
France	Centre hospitalier de Pernignan	Perpignan
France	Hôpital Pontchaillou	Rennes
France	Hôpital Purpan	Toulouse
France	Hôpital Gustave Dron	Tourcoing
France	Hôpital Bretonneau	Tours

Sponsors (2)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)	ViiV Healthcare

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Virological success without any intercurrent event leading to interrupt the strategy of the trial (analysis)	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	Evolution of CD4 and CD8 lymphocytes count (analysis)	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
Secondary	Percentage of participants who discontinued the strategy of the trial for toxicity or with adverse event of grade 3 or 4 (analysis)		week 56
Secondary	Profile of resistance mutations in plasma in case of virological failure		week 56
Secondary	Percentage of participants with plasma HIV RNA < 1 cp/mL		Day 0, week 8, week 32 and week 56
Secondary	Influence of total DNA on the occurrence of virological failure or blip	Influence of total DNA at Day 0 on the occurrence of virological failure or blip	from Day 0 to week 56
Secondary	Measure of concentrations of dolutegravir(Tivicay®) and lamivudine(Epivir®) in case of virological failure or with a blip		week 56
Secondary	Measure of adherence to treatment (self-reported)		Day 0, week 4, week 8, week 32 and week 56
Secondary	Measure of quality of life (self-reported)		Day 0, week 8 and week 56
Secondary	Comparison of Medico-economic substudy (analysis)	Evaluation of medico-economic aspects. Evaluate the direct medical cost related to dolutegravir and lamivudine versus the cost of the previous treatment.	week 56
Secondary	Sperm substudy measure of concentration	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

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