A retrospective, cohort-based survey of patients using twice-daily indinavir plus 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 indi navir 800 mg + ritonavir 100 mg twice daily or indinavir 400 mg + ritonavir 300 mg twice daily. Methods: Data were extracted from a database of samples sent to our laborat ory for measurement of indinavir + ritonavir plasma concentrations. Patient characteristics, safety, and efficacy measurements were collected by retro spective 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 occu rred in 22.1% and 34.9% of the patients in the 800/100 and the 400/400 grou ps, respectively. Viral load data were analyzed for patients who switched f rom 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% (40 0/400 group) had an undetectable viral load and this increased to 77% and 7 0%, respectively, during follow-up. Patients who switched to the 400/400 gr oup discontinued treatment more frequently than patients who switched to th e 800/100 group (70% vs. 26%, p = .008). Conclusions: Indinavir + ritonavir regimens show improved pharmacokinetic p roperties, allowing twice-daily dosing with feud. Clinical data suggest tha t safety and efficacy is at least as good as with indinavir three-times-dai ly regimens without ritonavir. Prospective, comparative trials are needed t o properly assess the role in HIV therapy of these twice-daily indinavir ritonavir regimens.