HIV-1 resistance rarely observed in patients using darunavir once-daily regimens across clinical studies
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 patients 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%).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
HIV clinical trials - 18(2017), 5-6 vom: 01. Nov., Seite 196-204 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lathouwers, Erkki [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.07.2018 Date Revised 06.09.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/15284336.2017.1387690 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM278099939 |
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| 245 | 1 | 0 | |a HIV-1 resistance rarely observed in patients using darunavir once-daily regimens across clinical studies |
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| 500 | |a Date Completed 09.07.2018 | ||
| 500 | |a Date Revised 06.09.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a OBJECTIVE: To summarize the development (or identification) of post-baseline resistance (RAMs and antiretroviral phenotypic susceptibility) among patients receiving darunavir QD dosing | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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%) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Antiretroviral | |
| 650 | 4 | |a Darunavir once daily | |
| 650 | 4 | |a Genotypic resistance | |
| 650 | 4 | |a Human immunodeficiency virus-1 | |
| 650 | 4 | |a Phenotypic resistance | |
| 650 | 4 | |a Resistance | |
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| 700 | 1 | |a Luo, Donghan |e verfasserin |4 aut | |
| 700 | 1 | |a Seyedkazemi, Sareh |e verfasserin |4 aut | |
| 700 | 1 | |a De Meyer, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Kimberley |e verfasserin |4 aut | |
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