Pharmacokinetics of Once-Daily Darunavir/Ritonavir With and Without Etravirine in Human Immunodeficiency Virus-Infected Children, Adolescents, and Young Adults

Abstract

The results suggest that DRV/r QD with ETR 400 mg QD or 200 mg BID is appropriate and support further evaluation of the safety and efficacy of the once-daily regimen in older children, adolescents, and young adults.

Pharmacokinetics of Darunavir/Ritonavir With Etravirine Both Twice Daily in Human Immunodeficiency Virus-Infected Adolescents and Young Adults: Table 1.

“…The ETR PK parameters we observed (AUC 0-12 5.2 mg ×hour/L and C 0 0.33 mg/L) were similar to those reported in the DUET study in adults [6] and in a recent population PK analysis of ETR in HIV-infected children aged 6 to 17 years (5.2 [4.3] mg × hour/L and 0.35 [0.34] mg/L, respectively) (PIANO study, NCT00665847) [10] and consistent with the levels observed when ETR was combined with DRV/r once daily [5].…”

“…Due to the observational nature of the study, a detailed assessment of the efficacy and safety was not possible; however, comparable exposure with the adult drug exposure data demonstrating safety and efficacy is indicative that the DRV/r/ ETV dosing studied is appropriate. Recent results of once-daily DRV/r with ETR (400 mg QD or 200 mg BID) have also suggested that the interaction is minimal in this population [5]. In conclusion, our data suggest that the current recommendation of DRV/r (600/100 mg) with ETR (200 mg) BID ETR is appropriate in adolescents and young adults.…”

“…Blood samples were processed, and plasma was stored at or below −20°C until analysis. Details of the DRV, RTV, and ETR assays methodologies have been previously described [5]. The primary outcome measure was the area under the plasma concentration-time curve (AUC) over the dosing interval.…”

Optimizing Pediatric Dosing Recommendations and Treatment Management of Antiretroviral Drugs Using Therapeutic Drug Monitoring Data in Children Living With HIV

“…It must be noted that all patients in the pediatric trials of QD DRV, except in the study by Chokephaibulkit et al, had a C trough above 0.55 mg/L, the EC 50 for susceptible viruses (see Table 3 , Supplemental Digital Content 2 , http://links.lww.com/TDM/A324), 81 and all children had high viral suppression rates regardless of decreased AUC compared with adult AUC. 75,76,80,82,83…”