Multicentric Open-label Study of Switch From Abacavir/Lamivudine Fixed Dose Combination Plus Nevirapine to Abacavir/Lamivudine/Dolutegravir in Virologically Suppressed HIV-1 Infected Adults (SWAD)

Study Overview
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Brief Summary
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Abacavir/Lamivudine + Nevirapine (ABC/3TC + NVP) is a very effective and well tolerable regimen on the long-term. However this regimen comprises 2 pills per day. Abacavir/Lamivudine/Dolutegravir (ABC/3TC/DTG) offers simplification with a single pill per day with no food constraints, Dolutegravir (DTG) having the advantage over Nevirapine (NVP) of high potency, higher genetic barrier to resistance, with a very good safety profile. The objective of this study is to evaluate the virologic safety (maintenance of virologic suppression) after switching from ABC/3TC + NVP to ABC/3TC/DTG in 50 HIV-1 infected adults with prolonged HIV RNA suppression on ABC/3TC + NVP, as well as clinical and laboratory safety. Because nevirapine is a strong inducer of hepatic enzymes, pharmacocinetic (PK) assessment will be performed in all patients in the first weeks after switch and 24-hours PK in a subset of 10 patients after 5 days of DTG addition to current regimen, before switching to ABC/3TC/DTG.

Official Title
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Phase 2 Multicentric Open-label Study of Switch From Abacavir/Lamivudine Fixed Dose Combination Plus Nevirapine to Abacavir/Lamivudine/Dolutegravir in Virologically Suppressed HIV-1 Infected Adults

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: Abacavir/Lamivudine/Dolutegravir


Participation Criteria
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Eligibility Criteria
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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 On antiretroviral treatment with nevirapine (400 mg per day) plus abacavir/lamivudine for more than 6 months; Nevirapine 400 mg/day being administered as either 1 x 200 mg IR x 2/day or 2 x 200 mg IR qd or 1 x 400 mg XR qd No history of prior virologic failure on antiretroviral therapy HIV-1 RNA < 50 copies/ml for more than 1 year, No major IAS-USA nucleoside reverse transcriptase inhibitors or integrase inhibitors resistance mutations on genotypic testing on last plasma sample with HIV-1 RNA > 500 c/mL (if available) HLA-B*5701 negative test Subjects covered by Health Insurance Exclusion Criteria: Woman of child-bearing potential without effective contraception method. 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abacavir/Lamivudine/Dolutegravir<br>Patients switched from their ongoing treatment of ABC/3TC + NVP to ABC/3TC/DTG. | Drug: Abacavir/Lamivudine/Dolutegravir<br>* At Day 1 (D1): group 1 will switch their ongoing treatment of ABC/3TC + NVP to ABC/3TC/DTG ; group 2 will continue NVP and switch ABC/3TC to ABC/3TC/DTG for 6 days (D-5 to D0), then stop NVP from D1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with plasma HIV-1 RNA < 50 copies/mL at week 12 |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with Plasma HIV-1 RNA < 50 copies/ml at W24 |  | Week 24 | 
| Percentage of patients with Plasma HIV-1 RNA < 50 copies/ml at W48 |  | Week 48 | 
| Percentage of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W12 |  | Week 12 | 
| Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W24 |  | Week 24 | 
| Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W36 |  | Week 36 | 
| Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W48 |  | Week 48 | 
| Percentage of patients with adverse event of any Grade over 12 weeks |  | Week 12 | 
| Percentage of patients with adverse event of Grade 3 or 4 over 48 weeks |  | Week 48 | 
| CD4 and CD8 measurement | Changes in CD4 and CD8 counts over 48 weeks | Week 48 | 
| Serum creatinine and GFR (MDRD) measurement | Changes in serum creatinine, and GFR (MDRD) from W2 to W48 | Week 48 | 
| Urinary albumine:creatinine ratio measurement | Change in urinary albumine:creatinine ratio over 48 weeks | Week 48 | 
| Fasting lipids measurement | Changes in fasting lipids over 48 weeks | Week 48 | 
| Plasma concentration of NVP between Week 0 (W0) and Week 2 (W2) | The mean plasma concentration of nevirapine is measured between W0 and W2 (D0, W1, W2) | Week 2 | 
| Plasma concentration of dolutegravir between W0 and W12 | The mean plasma concentration of dolutegravir is measured between W0 and W12 (W1, W2, W4, W12) | Week 12 | 
| CD14 and usCRP measurement over 48 weeks | Changes in sCD14 and usCRP over 48 weeks (stored plasma) | Week 48 | 
| Evaluation of patient's satisfaction with HIVTSQs and HIVTSQc questionnaires | Patient's satisfaction, evaluated with self-administered questionnaires HIVTSQs and HIVTSQc | Week 48 | 
| Plasma concentration of DTG on 24h at D0 and Week 2 | 24h PK parameters of DTG (D0, after 5 days of combination of ABC/3TC + NVP + DTG) with and without NVP (D14) | Week 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1 infection, Nevirapine, Dolutegravir, Anti-retroviral agents