Virological characterization of patients failing darunavir/ritonavir or lopinavir/ritonavir treatment in the ARTEMIS study: 96-week analysis.

BACKGROUND: In the Phase III ARTEMIS Trial, treatment-naive patients received once-daily darunavir/ritonavir (DRV/r) 800/100 mg (n = 343) or lopinavir/ritonavir (LPV/r) 800/200 mg (total daily dose; n = 346) plus fixed-dose tenofovir disoproxil fumarate/emtricitabine. The primary outcome measure was non-inferiority of DRV/r versus LPV/r (HIV type-1 [HIV-1] RNA<50 copies/ml). Here, a detailed 96-week resistance analysis is presented.
METHODS: Virological failures (VFs) were defined as patients who had lost (rebounders) or who had never achieved (never suppressed) HIV-1 RNA < 50 copies/ml after week 12. Genotypic and phenotypic determinations were performed on plasma samples with HIV-1 RNA ≥ 50 copies/ml. The end point was defined as the last on-treatment visit with available genotype and/or phenotype.
RESULTS: The VF rate was significantly lower in DRV/r (12%, n = 40) versus LPV/r patients (17%, n = 59; P = 0.0437). Among DRV/r patients, 24 rebounded and 16 were never suppressed, whereas among LPV/r patients, 33 rebounded and 26 were never suppressed. Transient HIV-1 RNA increases (≥ 50 copies/ml) occurred in 50% (n = 12) DRV/r and 48% (n = 16) LPV/r rebounders; these viral levels returned to undetectable by end point without any changes to the study regimen. No major (primary) protease inhibitor (PI) resistance-associated mutations (RAMs) developed in VFs with an available genotype at baseline and end point, and almost all developing minor PI RAMs were polymorphic. At end point, all VFs with available phenotypes at baseline and end point remained susceptible to all PIs, including study PIs.
CONCLUSIONS: The VF rate was lower with DRV/r than LPV/r. The findings of this resistance analysis confirmed the lack of development of major PI RAMs and the preservation of phenotypic susceptibility to all PIs in patients with VF.