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)

Sponsor

Nantes University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02067767

Collaborator

(none)

Enrollment

Locations

Arm

21.9

Duration (Months)

26.5

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection	Drug: Abacavir/Lamivudine/Dolutegravir	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

53 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2014

Actual Primary Completion Date :

Dec 1, 2015

Actual Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abacavir/Lamivudine/Dolutegravir Patients switched from their ongoing treatment of ABC/3TC + NVP to ABC/3TC/DTG.	Drug: Abacavir/Lamivudine/Dolutegravir 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.

Arm

Intervention/Treatment

Experimental: Abacavir/Lamivudine/Dolutegravir

Patients switched from their ongoing treatment of ABC/3TC + NVP to ABC/3TC/DTG.

Drug: Abacavir/Lamivudine/Dolutegravir

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.

Outcome Measures

Primary Outcome Measures

Percentage of patients with plasma HIV-1 RNA < 50 copies/mL at week 12 [Week 12]

Secondary Outcome Measures

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 [Week 48]
Changes in CD4 and CD8 counts over 48 weeks
Serum creatinine and GFR (MDRD) measurement [Week 48]
Changes in serum creatinine, and GFR (MDRD) from W2 to W48
Urinary albumine:creatinine ratio measurement [Week 48]
Change in urinary albumine:creatinine ratio over 48 weeks
Fasting lipids measurement [Week 48]
Changes in fasting lipids over 48 weeks
Plasma concentration of NVP between Week 0 (W0) and Week 2 (W2) [Week 2]
The mean plasma concentration of nevirapine is measured between W0 and W2 (D0, W1, W2)
Plasma concentration of dolutegravir between W0 and W12 [Week 12]
The mean plasma concentration of dolutegravir is measured between W0 and W12 (W1, W2, W4, W12)
CD14 and usCRP measurement over 48 weeks [Week 48]
Changes in sCD14 and usCRP over 48 weeks (stored plasma)
Evaluation of patient's satisfaction with HIVTSQs and HIVTSQc questionnaires [Week 48]
Patient's satisfaction, evaluated with self-administered questionnaires HIVTSQs and HIVTSQc
Plasma concentration of DTG on 24h at D0 and Week 2 [Week 2]
24h PK parameters of DTG (D0, after 5 days of combination of ABC/3TC + NVP + DTG) with and without NVP (D14)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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