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)

NCT ID: NCT02067767

Last Updated: 2016-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2015-12-31

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.

Conditions

HIV-1 Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Abacavir/Lamivudine/Dolutegravir

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

Group Type: EXPERIMENTAL

Abacavir/Lamivudine/Dolutegravir

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

François RAFFI, Pr

Role: STUDY_CHAIR

Nantes University Hospital

Locations

La Roche-sur-Yon Hospital

La Roche-sur-Yon, , France

Nantes University Hospital

Nantes, , France

Countries

France

References

Dailly E, Allavena C, Gregoire M, Reliquet V, Bouquie R, Billaud E, Hernando H, Bouchez S, Deslandes G, Hall N, Jolliet P, Raffi F. Influence of nevirapine administration on the pharmacokinetics of dolutegravir in patients infected with HIV-1. J Antimicrob Chemother. 2015 Dec;70(12):3307-10. doi: 10.1093/jac/dkv245. Epub 2015 Aug 13.

Reference Type: DERIVED

PMID: 26271944 (View on PubMed)

Other Identifiers

RC13_0230

Identifier Type: -

Identifier Source: org_study_id