HIV-1 resistance rarely observed in subjects using darunavir once-daily regimens across clinical studies

Background: Darunavir 800 mg once daily (QD) is indicated for HIV-1-infected treatment-naive and treatmentexperienced (without darunavir resistance-associated mutations [RAMs]) individuals, and has been evaluated in phase 2/3 studies with durations between 48 and 192 weeks. Objective: To summarize the development (or identification) of post-baseline resistance (RAMs and antiretroviral phenotypic susceptibility) among subjects receiving darunavir QD dosing. Methods: Seven phase 2/3 studies with available genotypes/phenotypes for subjects treated with ritonavir-or cobicistat-boosted darunavir 800 mg QD regimens were assessed: ARTEMIS (NCT00258557; n = 343), GSUS- 299-0102 (NCT01565850; n = 153), GS-US-216-0130 (NCT01440569; n = 313), ODIN (NCT00524368; n = 294), INROADS (NCT01199939; n = 54), MONET (NCT00458302; n = 256), and PROTEA (NCT01448707; n = 273). Genotypic analyses were conducted at baseline (except switch studies enrolling virologically suppressed subjects [MONET, PROTEA]). Criteria for post-baseline resistance testing and evaluation of the development (or identification [switch studies]) of RAMs (respective IAS-USA mutations) varied slightly across studies. Results: Among 1686 subjects treated with darunavir 800 mg QD regimens, 184 had protocol-defined virologic failure; 182 had post-baseline genotypes analyzed. Overall, 4/1686 (0.2%) developed (or had identified [switch studies]) primary protease inhibitor and/or darunavir RAMs (ARTEMIS, n = 1; GS-US-216-0130, n = 1; ODIN, n = 1; MONET, n = 1). Only 1/1686 (< 0.1%) subject lost darunavir phenotypic susceptibility (ODIN; possibly related to prior ritonavir-boosted lopinavir virologic failure). Among 1103 subjects using a nucleos(t) ide reverse transcriptase inhibitor (N[t] RTI) backbone, 10 (0.9%) developed >= 1 N(t) RTI RAM (8 had the emtricitabine RAM M184I/V). Conclusions: Darunavir has a high genetic barrier to resistance. Across a diverse population of HIV-1-infected subjects treated with darunavir 800 mg QD regimens, the development of darunavir resistance was rare (< 0.1%).