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

Abstract

Background: Darunavir 800 mg once daily (QD) is indicated for HIV-1–infected treatment-naïve and treatment-experienced (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), GS-US-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%).

Keywords:

• Darunavir once daily
• Human immunodeficiency virus-1
• Resistance
• Genotypic resistance
• Resistance-associated mutations
• Phenotypic resistance
• Antiretroviral

Acknowledgments

The authors would like to thank Anne Ghys of Janssen Infectious Diseases BVBA for her contributions. Medical writing support was provided by Courtney St. Amour, PhD, of MedErgy, and was funded by Janssen Scientific Affairs, LLC.