HIV-1 infection MedDRA version: 18.0 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: Dolutegravir/Abacavir/Lamivudine
Pharmaceutical Form: Tablet
Trade Name: Viramune LP
Pharmaceutical Form: Tablet
Sponsors
CHU de Nantes
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patient with confirmed HIV-1 infection (HIV antibody positive confirmation prior to screening) • Age = 18 years • Written informed consent • Male patient or non-pregnant, non-lactating female patient (Women of childbearing age must have a negative serum pregnancy test at screening. All female participants of childbearing potential must use contraception for the month preceding study entry and for the entire duration of the study. Recommended contraception during the trial is mechanical + a second method other than an oral contraceptive) • On antiretroviral treatment with nevirapine (400 mg per day) plus abacavir/lamivudine for more than 6 months • No history of prior virologic failure on antiretroviral therapy • HIV-1 RNA 500 c/mL (if available) • HLA-B*5701 negative test • Subjects covered by Health Insurance Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Woman of child-bearing potential without effective contraception method. For contraception during the trial all women must use a combination of mechanical method and a second method other than an oral contraceptive. Oral contraceptives are not to be used during the trial. Pregnant or breastfeeding woman. • Woman expecting to conceive during the study period • HIV-2 co-infection • Any prior exposure to integrase inhibitor(s) • plasma HIV-1 RNA > 50 c/mL in the past year • Creatinine clearance < 60 ml/mn (estimated glomerular filtration rate according to the MDRD equation), • Alkaline phosphatase, ASAT or ALAT = 5 times the upper limit of the norm (ULN) • Patient with history of decompensated liver disease • Any major IAS-USA mutation conferring resistance to one or more of reverse transcriptase or integrase inhibitors on genotypic testing at screening (DNA genotype) or on any historical plasma genotype if available. Any previous genotype result is valid, with no time limit, as long as the original test result is documented. • Mycobacteriosis under treatment • Malignancy requiring chemotherapy or radiotherapy • Positive HBs Ag • HCV infection for which specific treatment is ongoing or planned during the study • Known hypersensitivity to one of the trial drugs, the metabolites or formulation excipients • Concomitant therapy with antacids or H2 antagonists • Contraindicated concomitant treatment • Anticipated non-compliance with the protocol • Participation in another clinical trial with an on-going exclusion period at screening • Subject under legal guardianship or incapacitation • Subject, who in the opinion of the investigator, is unable to complete the study period
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective is to evaluate virologic safety, e.g. maintenance of virologic suppression, after 12 weeks of switch from NVP + ABC/3TC to DTG/ABC/3TC.;Secondary Objective: - to evaluate pharmacokinetic of NVP and DTG after swtiching from NVP to DTG. The objective is to assess residual concentrations of NVP over 2 weeks following NVP cessation and Cmin of DTG over the first 12 weeks following NVP-DTG switch to determine the extent of potential inducing effect of NVP on DTG. - to assess DTG PK with and without concomitant NVP administration - to assess maintenance of virologic suppression through 48 weeks - to evaluate safety and tolerability - to evaluate treatment satisfaction;Primary end point(s): The primary endpoint is the proportion of patients maintaining plasma HIV-1 RNA below 50 copies/mL at week 12.;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - 24h PK parameters of DTG (D0, after 5 days of combination of ABC/3TC + NVP + DTG) with and without NVP (D14) - Plasma HIV-1 RNA < 50 c/ml at W24 - Plasma HIV-1 RNA < 50 c/ml at W48 - Proportion of patients with undetectable plasma viral load (< 1 c/ml or signal not detected) at D0, W12, W24, W36, W48 - Proportion with AE of any Grade over 12 weeks - Proportion of patients with AE of Grade 3 or 4 over 48 weeks - Proportion of patients with AE leading to treatment discontinuation - Changes in CD4 and CD8 counts over 48 weeks - Changes in serum creatinine, and GFR (MDRD) from W2 to W48 - Change in urinary albumine:creatinine ratio over 48 weeks - Changes in fasting lipids over 48 weeks - Mean Cmin of nevirapine between W0 and W2 (D0, W1, W2) - Mean Cmin of dolutegravir between W0 and W12 (W1, W2, W4, W12) - Patient’s satisfaction, evaluated with self-administered questionnaires HIVTSQs and HIVTSQc - Changes in sCD14 and usCRP over 48 weeks (stored plasma);Timepoint(s) of evaluation of this end point: 48 weeks | — |
Countries
France
Contacts
Public ContactKarine NEAU
CHU de Nantes
Outcome results
None listed