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Lack of Interaction between Etravirine and Raltegravir plus Darunavir/Ritonavir when Combined in Treatment Experienced Patients:
a Substudy of the ANRS 139 TRIO Trial
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Reported by Jules Levin
CROI 2010 Feb SF
Aurelie Barrail-Tran1, Yazdan Yazdanpanah2, Catherine Fagard3, Celine Colin3, Christophe Piketty4, Christine Katlama5, Diane Descamps6, Jean-Michel Molina7, Genevieve Chene3, Anne-Marie Taburet*1, and ANRS 139 study group1Hospital Bicetre APHP, Paris France∼ 2Hospital Tourcoing, France∼ 3INSERM U897, Bordeaux, France∼ 4Hospital Pompidou APHP, Paris, France∼ 5Hospital Pitie Salpetriere APHP, Paris, France∼ 6Hospital Bichat APHP, Paris, France∼ and 7Hospital Saint louis APHP, Paris, France
Anne-Marie Taburet
Hôpital Bicetre AP/HP
78 rue du General Leclerc
94270 Kremlin Bicetre FRANCE
Tel: 33 1 45 21 29 64 / Fax: 33 1 45 21 28 60
E-Mail: anne-marie.taburet@bct.aphp.fr
ABSTRACT
Background: In patients with resistant viruses and few remaining treatment options, the combination of raltegravir, etravirine, and darunavir/ritonavir results in excellent virologic efficacy (primary analysis of ANRS139 TRIO). Exposure and pharmacokinetic (PK) parameters of combined antiretroviral drugs are poorly documented in such patients. A pharmacokinetic study was conducted in a sub group of patients included in the TRIO study to evaluate these parameters.
Methods: Patients who volunteered to participate, received raltegravir (400 mg 2x daily) and darunavir/r (600/100 mg 2x daily) from day 1 and etravirine (200 mg 2x daily) was started on day 7 of the study. Drugs were administered with a light meal. Blood samples for drug assay were drawn on days 6 and 28 at regular time intervals during a dosing interval. All drugs were assayed by HPLC with UV detection. Lower limit of quantification was 25 ng/mL for all drugs except raltegravir (10 ng/mL). Non compartmental PK parameters were calculated. Log transformed parameters were compared between the two periods by analysis of variance.
Results: Twelve HIV-1 infected patients enrolled in the trial and 10 completed the study. There was 1 female study participant, and the median age was 46 (18 to 59) years old. All patients had a ritonavir-boosted protease inhibitor containing regimen at inclusion. Optimized background therapy included 1 or 2 nucleoside analogs and enfuvirtide (2 patients). Baseline median (and range) of plasma HIV RNA and CD4 cells were 4.1 (1.9 to 5.1) log copies/mL and 304 (0 to 579) cells/mL, respectively. The Table below summarizes PK parameters on Days 6 and 28. None of the pharmacokinetic parameters were significantly different between the two periods. No serious adverse event was recorded. One patient failed (HIV-RNA >50 copies/mL at week 24), due to lack of treatment compliance.
Conclusions: Parameters are in the expected range and etravirine does not impair significantly raltegravir or darunavir PK parameters. However, raltegravir pharmacokinetics were found to be highly variable regardless to etravirine addition.
BACKGROUND
In patients with resistant viruses and few remaining treatment options, the combination of raltegravir, etravirine and darunavir/ritonavir results in excellent virologic efficacy (primary analysis of ANRS 139 TRIO). Exposure and pharmacokinetic (PK) parameters of combined antiretroviral drugs are poorly documented in such patients. A pharmacokinetic study was conducted in a subgroup of patients included in the TRIO study to evaluate these parameters.
Raltegravir, darunavir, ritonavir and etravirine pharmacokinetics
RESULTS
Pharmacokinetics parameters at week 1 (without etravirine) and week 4 (with etravirine)
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