The absence of primary PI mutations does not imply clinical results.
* Phenotypic data were determined by Antivirogram®. In this test, resistance was defined as a fold change in the 50% effective concentration above the biological/clinical cutoff.
† Study 130: An open-label, single-arm, 48-week, Phase 3 clinical trial evaluating the safety and efficacy of once-daily darunavir, or DRV, 800 mg (2 x 400 mg) + cobicistat, or COBI, 150 mg in HIV-1–infected TN adults (n=295) and TE adults (n=18) with HIV-1 RNA ≥1000 copies/mL and no DRV RAMs (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, and L89V). PhenoSense® GT assay; samples with >400 HIV-1 RNA copies/mL were analyzed.
‡ Resistance analysis conducted in patients who had paired genotypic data at baseline and end point.
§ None of the subjects had a decreased susceptibility to DRV at virologic failure.
¶ One TE patient developed a DRV resistance-associated substitution, which was not associated with a decreased susceptibility to DRV. In addition, the patient did not have decreased susceptibility to other PIs. Two patients (one TE and one TN) developed an NRTI resistance-associated substitution, which was associated with a decreased susceptibility to the NRTIs included in their treatment regimens.
# ODIN: A randomized, open-label, 48-week, Phase 3 noninferiority clinical trial comparing darunavir 800 mg coadministered with ritonavir 100 mg once daily vs darunavir 600 mg coadministered with 100 mg ritonavir twice daily in TE adult patients with viral load >1000 copies/mL and no DRV RAMs (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, and L89V). 60 patients had paired genotypic data at baseline and end point.
** One patient, who had previously been treated with lopinavir/ritonavir, developed PI mutations V32I, L76V, and I84V, which in combination were associated with a 24-fold decreased susceptibility to DRV.
PhenoSense GT is a registered trademark of Monogram Biosciences.
ARV=antiretroviral; DRV=darunavir; DRV/r=darunavir coadministered with ritonavir; LPR/r=lopinavir/ritonavir; NRTI=nucleoside reverse transcriptase inhibitor; OBR=optimized background regimen; PI=protease inhibitor; RAM=resistance-associated mutation; TDF/FTC=tenofovir disoproxil fumarate/emtricitabine; TE=treatment experienced; TN=treatment naïve; VF=virologic failure.
Reference: 1. Data on file. Janssen Therapeutics, Division of Janssen Products, LP.