Volume 13 Supplement 4
Efficacy of once daily darunavir/ritonavir 800/100 mg in PI/r-experienced HIV-1 infected patients with suppressed HIV-1 replication: the RADAR study
© Ghosn et al; licensee BioMed Central Ltd. 2010
Published: 8 November 2010
Once-daily darunavir/ritonavir 800/100 mg is licensed for first-line treatment and data are available in treatment-experienced patients with no resistance-associated mutations to darunavir. We designed an investigator study to evaluate the switch to once-daily darunavir/ritonavir 800/100 mg in treatment-experienced patients with suppressed HIV-1 replication on a twice-daily ritonavir-boosted protease-inhibitor (bid PI/r) containing regimen, i.e. in a setting where genotypic resistance test cannot be performed.
In this open-label, noncomparative, multicenter study, patients on a bid PI/r-containing triple combination, with suppressed viral replication, were switched to once-daily darunavir/r 800/100 mg containing triple combination. The primary endpoint was the proportion of patients with plasma HIV-RNA< 50 cp/ml 24 weeks after the switch. Detailed darunavir pharmacokinetic evaluation was performed at Week 4 (W4) and measurement of HIV-RNA in seminal plasma at baseline and W48 in a subset of patients.
85 patients were enrolled. All had HIV-RNA<50 cp/ml at screening with a median of 478 CD4/mm3 (range 40-1559) and pre-exposure to a median of 2 PI (1-5). 61 patients were currently on lopinavir/r, 18 on fosamprenavir/r, 4 on saquinavir/r and 2 on indinavir/r. At baseline, 15/16 patients had a seminal HIV-RNA< 100 cp/ml and 125 cp/ml for the remaining one. By intent-to-treat analysis (missing=failure), 78/85 patients (92%, CI95 [83;96]) maintained an HIV-RNA<50 cp/ml at W24. 7 patients experienced protocol-defined treatment failure between baseline and W24: 2 had confirmed viral rebound (88 and 70 cp/ml), 1 discontinued study treatment at W4 for adverse event, 3 withdrew their consent and 1 was lost to follow-up. By on-treatment analysis, 78/80 patients (97%, CI95 [91;99]) maintained an HIV-RNA<50 cp/ml at W24. At W4, the median area under the darunavir plasma concentration-time curve measured in 11 patients was 61 380 ng.h/ml (IQR 25-75% 42 094-97 313), darunavir median trough concentration 1340 ng/ml (907-1830) and darunavir half-life was 12.2 h (8.3-13.7). Tolerability of once-daily darunavir/r 800/100 mg was excellent.
In PI/r-experienced patients with suppressed viral replication on a bid PI/r-containing regimen, switching to once-daily darunavir/r 800/100 mg containing regimen was able to maintain suppression of viral replication and was safe in this setting where genotypic resistance test could not be performed.
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.