Ketoconazole is inferior to ritonavir as an alternative booster for saquinavir in a once daily regimen in Thai HIV-1 infected patients.

Objective: To improve the pharmacokinetics of protease inhibitors, boosting with low-dose ritonavir is performed. However, toxicity, storage conditions and high costs of antiretroviral treatment may necessitate interruption of ritonavir. Ketoconazole was investigated as a potential booster of once-daily (o.d.) saquinavir.

Methods: In a single-group, two-period design, 25 virologically and immunologically stable patients on saquinavir/ritonavir 2000/100 mg o.d. were switched to saquinavir/ketoconazole 2000/400 mg o.d. for 2 weeks. Two steady-state pharmacokinetic curves were recorded at both periods.

Results: Fourteen females and 11 male patients were included. Median age was 34 years [interquartile range (IQR), 32-42 years], body weight 54 kg (IQR, 47-59 kg) and body mass index 21 kg/m (19-23 kg/m). The mean saquinavir area under the curve (AUC) during boosting with ritonavir was 57.93 +/- 27.96 mg/h/l, maximum observed concentration (Cmax) was 7.50 +/- 3.45 mg/l and concentration at 24 h (Cmin) was 0.35 +/- 0.30 mg/l. When ketoconazole was used, the saquinavir AUC, Cmax, and Cmin were 12.00 +/- 6.97 mg/h/l, 2.43 +/- 1.35 mg/l and 0.03 +/- 0.04 mg/l, respectively.

Conclusion: Boosting with ketoconazole resulted in 80% lower exposure to saquinavir. Although saquinavir AUC might still be adequate for treatment, concentrations at 24 h reached levels below the recommended trough concentrations of 0.1 mg/l, which may result in selection of resistant HIV-1 viral strains. Therefore, boosting of saquinavir by ketoconazole is not recommended.