Clinical trial NCT02067767: 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)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
Keywords: HIV-1 infection
Nevirapine
Dolutegravir
Anti-retroviral agents
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2014-02-20
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of patients with plasma HIV-1 RNA < 50 copies/mL at week 12
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of patients with Plasma HIV-1 RNA < 50 copies/ml at W24
timeFrame: Week 24
measure: Percentage of patients with Plasma HIV-1 RNA < 50 copies/ml at W48
timeFrame: Week 48
measure: Percentage of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W12
timeFrame: Week 12
measure: Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W24
timeFrame: Week 24
measure: Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W36
timeFrame: Week 36
measure: Number of patients with undetectable plasma viral load (< 1 copies/ml or signal not detected) at W48
timeFrame: Week 48
measure: Percentage of patients with adverse event of any Grade over 12 weeks
timeFrame: Week 12
measure: Percentage of patients with adverse event of Grade 3 or 4 over 48 weeks
timeFrame: Week 48
measure: CD4 and CD8 measurement
timeFrame: Week 48
measure: Serum creatinine and GFR (MDRD) measurement
timeFrame: Week 48
measure: Urinary albumine:creatinine ratio measurement
timeFrame: Week 48
measure: Fasting lipids measurement
timeFrame: Week 48
measure: Plasma concentration of NVP between Week 0 (W0) and Week 2 (W2)
timeFrame: Week 2
measure: Plasma concentration of dolutegravir between W0 and W12
timeFrame: Week 12
measure: CD14 and usCRP measurement over 48 weeks
timeFrame: Week 48
measure: Evaluation of patient's satisfaction with HIVTSQs and HIVTSQc questionnaires
timeFrame: Week 48
measure: Plasma concentration of DTG on 24h at D0 and Week 2
timeFrame: Week 2
Other outcomes:
Locations:
city: La Roche-sur-Yon
country: France
facility: La Roche-sur-Yon Hospital
city: Nantes
country: France
facility: Nantes University Hospital
Study officials:
affiliation: Nantes University Hospital
name: François RAFFI, Pr
role: STUDY_CHAIR
References:
citation: 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.