Impact of rosiglitazone treatment on the bioavailability of antiretroviral compounds in HIV-positive patients.
OBJECTIVE
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 Cmax, Cmin and AUC were found in cases treated with efavirenz (n = 10) and lopinavir (n = 4). Mean Cmax 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 Cmax, Cmin and AUC (GMR of Cmax 0.95; 95% CI 0.9-1.0; GMR of Cmin 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.
Clinic for Gastroenterology, Hepatology, and Infectious Diseases, University Clinic Düsseldorf, Moorenstr. 5, 40225 Düsseldorf. oettem@med.uni-duesseldorf.de
M
M
Oette
M
M
Kurowski
T
T
Feldt
A
A
Kroidl
A
A
Sagir
C
C
Vogt
M
M
Wettstein
D
D
Häussinger
D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D019540:Area Under Curve; D001682:Biological Availability; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D019562:Viral Load
D019380:Anti-HIV Agents; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone