Impact of rosiglitazone treatment on the bioavailability of antiretroviral compounds in HIV-positive patients

Objectives: The insulin-sensitizer rosiglitazone is under investigation for therapy of HIV-associated lipodystrophy syndrome (LDS). Little is known about pharmacological interactions with antiretroviral (ARV) drugs. Methods: Therapeutic drug monitoring (TDM) of ARV drugs was performed in a prospective study before and at day 28 after start of treatment with 4 mg of rosiglitazone for combined LDS. Drug levels were measured in the morning fasting, and 0.5, 1, 2, 4, 6 and 8 h after standardized drug intake. Values were log-transformed for analysis. Results: Twelve males and six females were assessed; mean age was 50.7 years and mean CD4 cell count was 496 cells/mm(3). All patients had a viral load below 50 copies/mL, and backbone ARV therapy consisted of two or three nucleoside reverse transcriptase inhibitors in all cases. After administration of rosiglitazone, no significant differences in C-max, C-min and AUC were found in cases treated with efavirenz (n = 10) and lopinavir (n = 4). Mean C-max of nevirapine (n = 4) was reduced significantly [-0.44; 95% confidence interval (CI) -0.86 to -0.01]. Furthermore, there was a consistent trend to a reduction in the geometric mean ratio (GMR) of C-max C-min and AUC (GMR of C-max 0-95; 95% CI 0.9-1.0; GMR of C-min 0-89; 95% CI 0.65-1.13; GMR of AUC 0.96; 95% CI 0.91-1.01). Conclusions: Treatment with 4 mg of rosiglitazone for HIV-associated LDS is likely to reduce the bioavailability of nevirapine. Thus, routine TDM is recommended for patients treated with rosiglitazone and nevirapine. A therapy consisting of efavirenz or lopinavir seems to be without negative impact. Further studies on the interaction of rosiglitazone with ARV drugs are necessary.