Cargando…

Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance

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). W...

Descripción completa

Detalles Bibliográficos
Autores principales: Wolf, Eva, Boesecke, Christoph, Balogh, Annamaria, Bidner, Helen, Cordes, Christiane, Heiken, Hans, Krznaric, Ivanka, Kümmerle, Tim, Stellbrink, Hans-Jürgen, Schneider, Jochen, Spinner, Christoph D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425038/
https://www.ncbi.nlm.nih.gov/pubmed/34496848
http://dx.doi.org/10.1186/s12981-021-00384-6
_version_ 1783749777398169600
author Wolf, Eva
Boesecke, Christoph
Balogh, Annamaria
Bidner, Helen
Cordes, Christiane
Heiken, Hans
Krznaric, Ivanka
Kümmerle, Tim
Stellbrink, Hans-Jürgen
Schneider, Jochen
Spinner, Christoph D.
author_facet Wolf, Eva
Boesecke, Christoph
Balogh, Annamaria
Bidner, Helen
Cordes, Christiane
Heiken, Hans
Krznaric, Ivanka
Kümmerle, Tim
Stellbrink, Hans-Jürgen
Schneider, Jochen
Spinner, Christoph D.
author_sort Wolf, Eva
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8425038
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-84250382021-09-10 Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance Wolf, Eva Boesecke, Christoph Balogh, Annamaria Bidner, Helen Cordes, Christiane Heiken, Hans Krznaric, Ivanka Kümmerle, Tim Stellbrink, Hans-Jürgen Schneider, Jochen Spinner, Christoph D. AIDS Res Ther Short Report 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. BioMed Central 2021-09-08 /pmc/articles/PMC8425038/ /pubmed/34496848 http://dx.doi.org/10.1186/s12981-021-00384-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Short Report
Wolf, Eva
Boesecke, Christoph
Balogh, Annamaria
Bidner, Helen
Cordes, Christiane
Heiken, Hans
Krznaric, Ivanka
Kümmerle, Tim
Stellbrink, Hans-Jürgen
Schneider, Jochen
Spinner, Christoph D.
Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance
title Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance
title_full Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance
title_fullStr Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance
title_full_unstemmed Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance
title_short Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance
title_sort virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425038/
https://www.ncbi.nlm.nih.gov/pubmed/34496848
http://dx.doi.org/10.1186/s12981-021-00384-6
work_keys_str_mv AT wolfeva virologicoutcomesofswitchingtoboosteddarunavirplusdolutegravirwithrespecttohistoryofdrugresistance
AT boeseckechristoph virologicoutcomesofswitchingtoboosteddarunavirplusdolutegravirwithrespecttohistoryofdrugresistance
AT baloghannamaria virologicoutcomesofswitchingtoboosteddarunavirplusdolutegravirwithrespecttohistoryofdrugresistance
AT bidnerhelen virologicoutcomesofswitchingtoboosteddarunavirplusdolutegravirwithrespecttohistoryofdrugresistance
AT cordeschristiane virologicoutcomesofswitchingtoboosteddarunavirplusdolutegravirwithrespecttohistoryofdrugresistance
AT heikenhans virologicoutcomesofswitchingtoboosteddarunavirplusdolutegravirwithrespecttohistoryofdrugresistance
AT krznaricivanka virologicoutcomesofswitchingtoboosteddarunavirplusdolutegravirwithrespecttohistoryofdrugresistance
AT kummerletim virologicoutcomesofswitchingtoboosteddarunavirplusdolutegravirwithrespecttohistoryofdrugresistance
AT stellbrinkhansjurgen virologicoutcomesofswitchingtoboosteddarunavirplusdolutegravirwithrespecttohistoryofdrugresistance
AT schneiderjochen virologicoutcomesofswitchingtoboosteddarunavirplusdolutegravirwithrespecttohistoryofdrugresistance
AT spinnerchristophd virologicoutcomesofswitchingtoboosteddarunavirplusdolutegravirwithrespecttohistoryofdrugresistance
AT virologicoutcomesofswitchingtoboosteddarunavirplusdolutegravirwithrespecttohistoryofdrugresistance