{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:17:48Z","timestamp":1790813868692,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Long-acting (LA) injectable therapy with cabotegravir (CAB) and rilpivirine (RPV) is currently used as maintenance treatment for human immunodeficiency virus type 1, and has a low risk for virological failure (VF). Although the risk is low, the circumstances and impact of VF in the real-world setting merit further evaluation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed an in-depth clinical, virological, and pharmacokinetic analysis on the reasons behind and the impact of VF during LA CAB\/RPV therapy in 5 cases from the Netherlands. Genotypic resistance testing was performed after the occurrence of VF, and drug plasma (trough) concentrations were measured after VF was established and on any other samples to assess on-treatment drug levels. CAB and RPV drug levels that were below the first quartile of the population cutoff (\u2264Q1) were considered to be low.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Five cases who were eligible for LA CAB\/RPV experienced VF despite a low predicted risk at baseline. Genotypic resistance testing revealed extensive selection of nonnucleoside reverse transcriptase inhibitor\u2013associated mutations in all cases, and integrase strand transfer inhibitor mutations in 4 cases. All cases displayed low drug levels of either CAB, RPV, or both during the treatment course, likely contributing to the occurrence of VF. In 3 cases, we were able to identify the potential mechanisms behind these low drug levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This is the first in-depth multiple case analysis of VF on LA CAB\/RPV therapy in a real-world setting. Our observations stress the need to be aware for (evolving) risk factors and the yield of a comprehensive clinical, virological, and pharmacokinetic approach in case of failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciae016","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T14:36:26Z","timestamp":1704983786000},"page":"189-195","source":"Crossref","is-referenced-by-count":58,"title":["Virological Failure After Switch to Long-Acting Cabotegravir and Rilpivirine Injectable Therapy: An In-depth Analysis"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5601-4207","authenticated-orcid":false,"given":"Berend J","family":"van Welzen","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, University Medical Center Utrecht , Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven F L","family":"Van Lelyveld","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Spaarne Gasthuis , Hoofddorp\/Haarlem , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerjanne","family":"Ter Beest","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rijnstate Hospital , Arnhem , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jet H","family":"Gisolf","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rijnstate Hospital , Arnhem , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne E","family":"Geerlings","sequence":"additional","affiliation":[{"name":"Infectious Diseases, Department of Internal Medicine, Amsterdam University Medical Center, University of Amsterdam , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan 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Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Institute of Medical Innovation, Radboud University Medical Center , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie M J","family":"Wensing","sequence":"additional","affiliation":[{"name":"Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht , Utrecht , The Netherlands"},{"name":"Ezintsha, Department of Health, University of the Witwatersrand , Johannesburg , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"2024071918133077200_ciae016-B1","author":"European Medicines 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