HIV-1 Infection
Conditions
Keywords
dolutegravir(Tivicay®), lamivudine(Epivir®), HIV-1, efficacy, safety
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.
Interventions
DRUGdolutegravir (Tivicay®) - Phase 1
• Phase 1 (8 weeks) : switch of the third agent with dolutegravir(Tivicay®) 50 mg once a day.
DRUGlamivudine (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.
DRUGdolutegravir (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.
Sponsors
ViiV Healthcare
ANRS, Emerging Infectious Diseases
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Virological success without any intercurrent event leading to interrupt the strategy of the trial (analysis) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants who discontinued the strategy of the trial for toxicity or with adverse event of grade 3 or 4 (analysis) | week 56 | — |
| Profile of resistance mutations in plasma in case of virological failure | week 56 | — |
| Percentage of participants with plasma HIV RNA < 1 cp/mL | Day 0, week 8, week 32 and week 56 | — |
| Influence of total DNA on the occurrence of virological failure or blip | from Day 0 to week 56 | Influence of total DNA at Day 0 on the occurrence of virological failure or blip |
| Evolution of CD4 and CD8 lymphocytes count (analysis) | 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 |
| Measure of adherence to treatment (self-reported) | Day 0, week 4, week 8, week 32 and week 56 | — |
| Measure of quality of life (self-reported) | Day 0, week 8 and week 56 | — |
| Comparison of Medico-economic substudy (analysis) | week 56 | Evaluation of medico-economic aspects. Evaluate the direct medical cost related to dolutegravir and lamivudine versus the cost of the previous treatment. |
| Sperm substudy measure of concentration | 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 |
| Measure of concentrations of dolutegravir(Tivicay®) and lamivudine(Epivir®) in case of virological failure or with a blip | week 56 | — |
Countries
France
Outcome results
None listed