Background: Combinations of new classes of antiretroviral drugs are attractive options to avoid toxicity associated with nucleoside reverse transcriptase inhibitors (NRTIs) and to provide a full active regimen in patients with some degree of resistance to NRTIs. However, data on the pharmacokinetic (PK) profiles of these regimens are limited. We explore the plasma PK profile of raltegravir (RAL) at a dose of 400 mg twice a day plus darunavir/ritonavir (DRV/RTV) at a dose of 800/100 mg once a day in HIV-1-infected patients.
Methods: This was a pilot, open-label, fixed-sequence, prospective, single-center single-arm PK study. The treating physician chose an NRTI-sparing regimen because of toxicity or resistance mutations to NRTIs, which included DRV/RTV 800/100 mg once daily plus RAL 400 mg twice daily. All patients were RAL and DRV naive and had no evidence of protease inhibitor mutations. After at least 15 days on therapy, patients were admitted for a 24-hour PK study. Laboratory tests to assess efficacy and safety were performed at all study visits.
Results: Fifteen patients were included. The geometric mean values for DRV were AUC0-24 68,730 ng·h·mL [95% confidence interval (CI): 58,970-86,480], Ctrough 1330 ng/mL (95% CI: 1110-1760; IC-50 for wild-type and resistant HIV-1 strains was 55 and 550 ng/mL, respectively), Cmax 7630 ng/mL (95% CI: 6740-9000), and t1/2 10.9 hours (95% CI: 9.20-13.99). Geometric mean values for RAL were AUC0-12 3050 ng·h·mL (95% CI: 2530-5180); Ctrough 40 ng/mL (95% CI: 30-80), Cmax 970 ng/mL (95% CI: 840-2270), t1/2 2.68 hours (95% CI: 1.97-4.40). No adverse effects including rash or laboratory test abnormalities were noted. At week 24, the HIV-1 viral load was below 37 copies/mL in all patients.
Conclusions: Our data suggest that dual therapy with RAL 400 mg twice daily plus DRV/RTV 800/100 mg once daily had a favorable PK profile for both drugs and that short-term efficacy and tolerability of this combination were adequate.
Trial registration: ClinicalTrials.gov NCT01258374.