Occurrence of selective ritonavir nonadherence and dose-staggering in recipients of boosted HIV-1 protease inhibitor therapy.

BACKGROUND

The inhibitory effect of ritonavir on hepatic cytochrome P450 enzymes is a critical factor in achieving optimal levels of co-administered "boosted" protease inhibitors (PIs). Even though nonadherence to antiretroviral medications is a common phenomenon, the prevalence of selective ritonavir nonadherence and dosestaggering (i.e., separating ritonavir and boosted PI doses in time) are unknown.

METHODS

HIV-1-infected adults receiving a regimen containing ritonavir-boosted atazanavir or fosamprenavir were recruited into a prospective study of adherence and dosage timing of both agents. These parameters were measured over 24 weeks using the Medication Event Monitoring System (MEMS; Aardex, Union, California, USA). A subject was deemed to be selectively nonadherent to ritonavir if his/her adherence rate to the boosted PI exceeded that of ritonavir by >5%. Dose-staggering was defined as a temporal separation of boosted PI from its corresponding ritonavir dose of >4 hours but <12 hours.

RESULTS

The final study population consisted of 36 subjects. Three subjects (8.3%) were selectively nonadherent to ritonavir, 17 (47.2%) staggered any doses of ritonavir, and 3 (8.3%) staggered more than 5% of their ritonavir doses. Two of these three were also selectively nonadherent to ritonavir. There was no evident impact of these behaviors on HIV viral load (VL); all subjects who were selectively nonadherent to or frequently staggered doses of ritonavir had VL <75 copies/mL at 24 weeks.

CONCLUSIONS

Selective ritonavir nonadherence and dose-staggering occurs in a small but significant minority of boosted PI recipients.