HIV-1 Infection
Conditions
Keywords
HIV-1 infection, Nevirapine, Dolutegravir, Anti-retroviral agents
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.
Interventions
DRUGAbacavir/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.
Sponsors
Nantes University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of patients with plasma HIV-1 RNA < 50 copies/mL at week 12 | Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CD14 and usCRP measurement over 48 weeks | Week 48 | Changes in sCD14 and usCRP over 48 weeks (stored plasma) |
| 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 | — |
| 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) |
| 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) |
| 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) |
| Percentage of patients with adverse event of Grade 3 or 4 over 48 weeks | Week 48 | — |
Countries
France
Outcome results
None listed