Monitoring atazanavir concentrations with boosted or unboosted regimens in HIV-infected patients in routine clinical practice.
Although atazanavir pharmacokinetics and pharmacodynamics are related, the atazanavir plasma trough concentrations of patients on regimens that are not boosted by low doses of ritonavir may not be high enough to maintain viral suppression. In this cross-sectional study, the percentage of patients with atazanavir trough concentrations lower than the proposed minimum effective concentration was compared between HIV-infected patients receiving antiretroviral therapy with ritonavir-boosted (ATV/r, n = 31) or unboosted (ATV, n = 54) atazanavir in clinical practice. Blood samples were drawn 21 to 25 hours after the last atazanavir dose. Drug concentrations in plasma were determined by high-performance liquid chromatography and considered suboptimal if they were lower than 0.15 mg/L or potentially toxic if higher than 0.85 mg/L. The median (interquartile range) atazanavir concentration was 0.711 (0.394-0.914) mg/L in patients receiving ATV/r and 0.121 (0.052-0.209) mg/L in patients receiving ATV (P < 0.001). None of the patients receiving ATV/r and 62.9% of the subjects receiving ATV showed drug concentrations below 0.15 mg/L (odds ratio, 2.7; 95% confidence interval, 1.9-3.8; P < 0.001). In contrast, atazanavir concentrations were higher than 0.85 mg/L in 32.2% of the patients receiving ATV/r compared with 3.7% of the subjects receiving ATV (odds ratio, 8.7; 95% confidence interval, 2.0-37.2; P = 0.001). Atazanavir and total bilirubin concentrations in plasma were correlated. In conclusion, atazanavir trough concentrations may be lower than the proposed minimum effective concentration in a considerable percentage of HIV-infected patients receiving antiretroviral therapy with unboosted atazanavir. Therapeutic drug monitoring may be useful in this setting.
Moltó
José
J
Lluita contra la SIDA Foundation, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. jmolto@flsida.org
Santos
José Ramón
JR
Valle
Marta
M
Miranda
Cristina
C
Miranda
José
J
Blanco
Asunción
A
Negredo
Eugenia
E
Clotet
Bonaventura
B
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D001663:Bilirubin / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019438:Ritonavir; D001663:Bilirubin