Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance
© 2021. The Author(s)..
OBJECTIVE: The DUALIS study showed that switching to boosted darunavir (bDRV) plus dolutegravir (DTG; 2DR) was non-inferior to continuous bDRV plus 2 nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs; 3DR) in treatment-experienced virologically suppressed people living with HIV (PLWH). We analyzed virologic outcomes with respect to treatment history and HIV drug resistance.
DESIGN: Post hoc analysis of a randomized trial.
METHODS: Main inclusion criteria were an HIV RNA level < 50 copies/mL for ≥ 24 weeks and no resistance to integrase strand transfer inhibitors or bDRV. Resistance-associated mutations (RAMs) were interpreted using the Stanford HIVdb mutation list. Outcomes measures were 48-week virologic response (HIV RNA < 50 copies/mL, FDA snapshot) and HIV RNA ≥ 50 copies/mL (including discontinuation due to a lack of efficacy or reasons other than adverse events and HIV RNA ≥ 50 copies/mL, referred to as snapshot non-response).
RESULTS: The analysis population included 263 patients (2DR: 131, 3DR: 132): 90.1% males; median age, 48 years; CD4 + T-cell nadir < 200/µl, 47.0%; ≥ 2 treatment changes, 27.4%; NRTI, non-NRTI (NNRTI), and major protease inhibitor (PI) RAMs in 9.5%, 14.4%, and 3.4%, respectively. In patients with RAMs in the 2DR and 3DR groups, virologic response rates were 87.8% and 96.0%, respectively; the corresponding rates in those without RAMs were 85.7% and 81.8%. RAMs were unrelated to virologic non-response in either group. No treatment-emergent RAMs were observed.
CONCLUSIONS: DTG + bDRV is an effective treatment option without the risk of treatment-emergent resistance for PLWH on suppressive first- or further-line treatment with or without evidence of pre-existing NRTI, NNRTI, or PI RAMs.
TRIAL REGISTRATION: EUDRA-CT Number 2015-000360-34; registered 07 April 2015; https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000360-34/DE.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
AIDS research and therapy - 18(2021), 1 vom: 08. Sept., Seite 58 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wolf, Eva [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.09.2021 Date Revised 31.05.2022 published: Electronic EudraCT: 2015-000360-34 Citation Status MEDLINE |
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| doi: |
10.1186/s12981-021-00384-6 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 17.09.2021 | ||
| 500 | |a Date Revised 31.05.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a EudraCT: 2015-000360-34 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. The Author(s). | ||
| 520 | |a OBJECTIVE: The DUALIS study showed that switching to boosted darunavir (bDRV) plus dolutegravir (DTG; 2DR) was non-inferior to continuous bDRV plus 2 nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs; 3DR) in treatment-experienced virologically suppressed people living with HIV (PLWH). We analyzed virologic outcomes with respect to treatment history and HIV drug resistance | ||
| 520 | |a DESIGN: Post hoc analysis of a randomized trial | ||
| 520 | |a METHODS: Main inclusion criteria were an HIV RNA level < 50 copies/mL for ≥ 24 weeks and no resistance to integrase strand transfer inhibitors or bDRV. Resistance-associated mutations (RAMs) were interpreted using the Stanford HIVdb mutation list. Outcomes measures were 48-week virologic response (HIV RNA < 50 copies/mL, FDA snapshot) and HIV RNA ≥ 50 copies/mL (including discontinuation due to a lack of efficacy or reasons other than adverse events and HIV RNA ≥ 50 copies/mL, referred to as snapshot non-response) | ||
| 520 | |a RESULTS: The analysis population included 263 patients (2DR: 131, 3DR: 132): 90.1% males; median age, 48 years; CD4 + T-cell nadir < 200/µl, 47.0%; ≥ 2 treatment changes, 27.4%; NRTI, non-NRTI (NNRTI), and major protease inhibitor (PI) RAMs in 9.5%, 14.4%, and 3.4%, respectively. In patients with RAMs in the 2DR and 3DR groups, virologic response rates were 87.8% and 96.0%, respectively; the corresponding rates in those without RAMs were 85.7% and 81.8%. RAMs were unrelated to virologic non-response in either group. No treatment-emergent RAMs were observed | ||
| 520 | |a CONCLUSIONS: DTG + bDRV is an effective treatment option without the risk of treatment-emergent resistance for PLWH on suppressive first- or further-line treatment with or without evidence of pre-existing NRTI, NNRTI, or PI RAMs | ||
| 520 | |a TRIAL REGISTRATION: EUDRA-CT Number 2015-000360-34; registered 07 April 2015; https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000360-34/DE | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Darunavir | |
| 650 | 4 | |a Dolutegravir | |
| 650 | 4 | |a HIV drug resistance | |
| 650 | 4 | |a Integrase inhibitors | |
| 650 | 4 | |a Protease inhibitors | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a Heterocyclic Compounds, 3-Ring |2 NLM | |
| 650 | 7 | |a Oxazines |2 NLM | |
| 650 | 7 | |a Piperazines |2 NLM | |
| 650 | 7 | |a Pyridones |2 NLM | |
| 650 | 7 | |a dolutegravir |2 NLM | |
| 650 | 7 | |a DKO1W9H7M1 |2 NLM | |
| 650 | 7 | |a Darunavir |2 NLM | |
| 650 | 7 | |a YO603Y8113 |2 NLM | |
| 700 | 1 | |a Boesecke, Christoph |e verfasserin |4 aut | |
| 700 | 1 | |a Balogh, Annamaria |e verfasserin |4 aut | |
| 700 | 1 | |a Bidner, Helen |e verfasserin |4 aut | |
| 700 | 1 | |a Cordes, Christiane |e verfasserin |4 aut | |
| 700 | 1 | |a Heiken, Hans |e verfasserin |4 aut | |
| 700 | 1 | |a Krznaric, Ivanka |e verfasserin |4 aut | |
| 700 | 1 | |a Kümmerle, Tim |e verfasserin |4 aut | |
| 700 | 1 | |a Stellbrink, Hans-Jürgen |e verfasserin |4 aut | |
| 700 | 1 | |a Schneider, Jochen |e verfasserin |4 aut | |
| 700 | 1 | |a Spinner, Christoph D |e verfasserin |4 aut | |
| 700 | 0 | |a DUALIS Study Group |e verfasserin |4 aut | |
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