Interactions between atazanavir-ritonavir and tenofovir in heavily pretreated human immunodeficiency virus-infected patients.
The aim of the present study was to assess the pharmacokinetic behavior of atazanavir-ritonavir when it is coadministered with tenofovir disoproxil fumarate (DF) in human immunodeficiency virus (HIV)-infected patients. Eleven patients enrolled in Agence Nationale de Recherche sur le SIDA (National Agency for AIDS Research, Paris, France) trial 107 were included in this pharmacokinetic study. They received atazanavir at 300 mg and ritonavir at 100 mg once a day (QD) from day 1 to the end of study. For the first 2 weeks, their nucleoside analog reverse transcriptase inhibitor (NRTI) treatments remained unchanged. Tenofovir DF was administered QD from day 15 to the end of the study. Ongoing NRTIs were selected according to the reverse transcriptase genotype of the HIV isolates from each patient. The values of the pharmacokinetic parameters for atazanavir and ritonavir were measured before (day 14 [week 2]) and after (day 42 [week 6]) initiation of tenofovir DF and are reported for the 10 patients who completed the study. There was a significant decrease in the area under the concentration-time curve from 0 to 24 h (AUC(0-24)) for atazanavir with the addition of tenofovir DF (AUC(0-24) ratio, 0.75; 90% confidence interval, 0.58 to 0.97; P = 0.05). There was a trend for a decrease in the minimum concentrations of atazanavir and ritonavir in plasma when they were combined with tenofovir, but none of the differences reached statistical significance. The median decreases in the HIV RNA loads at week 2 and week 6 were 0.1 and 0.2 log copies/ml, respectively. In summary, our data are consistent with the existence of a significant interaction between atazanavir and tenofovir DF.
Taburet
Anne-Marie
AM
Clinical Pharmacy, Hospital Bicêtre-Assistance Publique Hôpitaux de Paris, 78 rue du Général Leclerc, 94270 Kremlin Bicêtre, France. anne-marie.taburet@bct.ap-hop-paris.fr
Piketty
Christophe
C
Chazallon
Corine
C
Vincent
Isabelle
I
Gérard
Laurence
L
Calvez
Vincent
V
Clavel
Francois
F
Aboulker
Jean-Pierre
JP
Girard
Pierre-Marie
PM
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D000069446:Atazanavir Sulfate; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D019438:Ritonavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D000068698:Tenofovir
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D009842:Oligopeptides; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D011725:Pyridines; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir