Pharmacokinetics of Reduced-Dose Indinavir/Ritonavir 400/100 Mg Twice Daily in HIV-1-Infected Thai Patients

Abstract

Objective

To study the pharmacokinetics of indinavir/ ritonavir 400/100 mg twice daily in antiretroviral-naive patients at Srinagarind Hospital in Khon Kaen, Thailand.

Methods

This was a steady-state, open-label pharmacokinetic study of 19 patients. A 12 h pharmacokinetic curve was recorded after an overnight fast. Plasma levels of indinavir and ritonavir were determined by a validated HPLC method. Virological failure was defined according to the most recent US Department of Health and Human Services guidelines as a viral load above 400 copies/ml at week 24.

Results

Median baseline values for CD4 and viral load were 13 cells/mm³ and 167000 copies/ml, respectively. The median (interquartile ranges) for indinavir AUC, C_max and C_min were 18.1 (15.3–23.8) mg/l•h, 4.1 (3.6–4.8) mg/l and 0.17 (0.12–0.30) mg/l, respectively. These values represent 37%, 39% and 24% of the AUC, C_max and C_min values found, respectively, for the indinavir/ritonavir 800/100 mg dose in HIV-1-infected Thai patients. Short-term virological response was satisfactory. There were three subjects with an indinavir C_min below the target value of 0.10 mg/l, of whom one had virological failure (33%). Among the other 16 subjects with an indinavir C_min above 0.10 mg/l, there was also one virological failure (6%) (P=0.30).

Conclusions

Indinavir exposure in this reduced-dose regimen of 400 mg with 100 mg ritonavir twice daily was more than dose-proportionally lower than previously observed with the indinavir/ritonavir 800/100 mg twice daily regimen. Therapeutic C_min levels of indinavir were achieved in >80% of the subjects and short-term virological response was satisfactory in this cohort of patients starting highly active antiretroviral therapy at an advanced disease stage with high baseline viral loads.