A retrospective, cohort-based survey of patients using twice-daily indinavir + ritonavir combinations: pharmacokinetics, safety, and efficacy.

OBJECTIVE: To describe the pharmacokinetics, safety, and efficacy of twice-daily indinavir + ritonavir regimens
DESIGN: A cohort-based survey of HIV-infected patients who either used indinavir 800 mg + ritonavir 100 mg twice daily or indinavir 400 mg + ritonavir 400 mg twice daily.
METHODS: Data were extracted from a database of samples sent to our laboratory for measurement of indinavir + ritonavir plasma concentrations. Patient characteristics, safety, and efficacy measurements were collected by retrospective chart review.
RESULTS: 100 Patients using 800-mg indinavir + 100-mg ritonavir twice daily and 32 patients using 400-mg indinavir + 400-mg ritonavir twice daily were eligible. Median peak and trough concentrations of indinavir were 6.8 and 0.77 mg/L in the 800/100 group and 2.6 and 0.45 mg/L in the 400/400 group. The most frequently found side effects were nausea and vomiting, which occurred in 22.1% and 34.9% of the patients in the 800/100 and the 400/400 groups, respectively. Viral load data were analyzed for patients who switched from 800-mg indinavir three times daily to one of the indinavir + ritonavir twice daily regimens. At the time of switch 63% (800/100 group) and 60% (400/400 group) had an undetectable viral load and this increased to 77% and 70%, respectively, during follow-up. Patients who switched to the 400/400 group discontinued treatment more frequently than patients who switched to the 800/100 group (70% vs. 26%, p =.008).
CONCLUSIONS: Indinavir + ritonavir regimens show improved pharmacokinetic properties, allowing twice-daily dosing with food. Clinical data suggest that safety and efficacy is at least as good as with indinavir three-times-daily regimens without ritonavir. Prospective, comparative trials are needed to properly assess the role in HIV therapy of these twice-daily indinavir + ritonavir regimens.