{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T23:41:03Z","timestamp":1787701263274,"version":"build-2784847793"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Klinikum der Universit\u00e4t M\u00fcnchen"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Infection"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cabotegravir (CAB) and rilpivirine (RPV) constitute the first complete non-oral ART regimen for HIV-1 treatment. Due to virologic failure (VF) with resistance in clinical trials, concerns persist regarding broader use in clinical practice. In particular, the role of trough drug concentrations in relation to viremia and VF remains unclear. This study explored the association between CAB and RPV trough concentrations in a retrospective, single-center study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed data from the HIV research and clinical care center MVZ M\u00fcnchen am Goetheplatz, Germany. Inclusion criteria were CAB and RPV long-acting therapy every 8 weeks without additional ART and availability of drug concentrations within 7 days before the next administration. A modified Wilcoxon test assessed differences in concentrations between samples with HIV-1 RNA\u2009&lt;\u200920 vs. \u226520 copies\/mL. Odds ratios (ORs) were estimated using generalized estimation equation (GEE) models, and ROC analysis identified potential alternative drug concentration thresholds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      A total of 737 samples from 185 individuals were included. Median CAB concentrations were 1,480\u00a0\u00b5g\/L (IQR: 1,097\u20131,955) vs. 1,180\u00a0\u00b5g\/L (879\u20131,570) for samples with HIV-1 RNA levels\u2009&lt;\u200920 copies\/mL vs. \u2265 20 copies\/mL, respectively (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001); for RPV, 77\u00a0\u00b5g\/L (53\u2013107) vs. 63\u00a0\u00b5g\/L (47\u201387) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001). Using ROC-derived thresholds, low concentrations of CAB (&lt;\u20091,240\u00a0\u00b5g\/L) or RPV (&lt;\u200976\u00a0\u00b5g\/L) were found in 11.5% and 25.4% of samples, respectively, and associated with ORs of 2.4 (1.5\u20134.0) and 2.3 (1.4\u20133.8) for HIV-1 RNA\u2009\u2265\u200920 copies\/mL.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Lower CAB and RPV concentrations were associated with viremia, particularly using the ROC-derived thresholds. Among individuals with VF and available drug concentration data, 87.5% had at least one drug below these thresholds. Further research on therapeutic drug monitoring is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s15010-025-02577-x","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T02:47:01Z","timestamp":1751597221000},"page":"2421-2431","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Trough concentrations of cabotegravir and rilpivirine and their association with detectable viral load in people with HIV on long-acting treatment"],"prefix":"10.1007","volume":"53","author":[{"given":"Sebastian","family":"Noe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Seybold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad","family":"Schabaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"von Krosigk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Wiese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Jonsson-Oldenb\u00fcttel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ivanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"2577_CR1","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.1093\/CID\/CIAD020","volume":"76","author":"ET Overton","year":"2023","unstructured":"Overton ET, Richmond G, Rizzardini G, et al. Long-Acting cabotegravir and rilpivirine dosed every 2 months in adults with human immunodeficiency virus 1 type 1 infection: 152-Week results from ATLAS-2\u00a0M, a randomized, Open-Label, phase 3b, noninferiority study. Clin Infect Dis. 2023;76:1646\u201354. https:\/\/doi.org\/10.1093\/CID\/CIAD020.","journal-title":"Clin Infect Dis"},{"key":"2577_CR2","doi-asserted-by":"publisher","first-page":"e668","DOI":"10.1016\/S2352-3018(21)00184-3","volume":"8","author":"C Orkin","year":"2021","unstructured":"Orkin C, Bernal Morell E, Tan DHS, et al. Initiation of long-acting cabotegravir plus rilpivirine as direct-to-injection or with an oral lead-in in adults with HIV-1 infection: week 124 results of the open-label phase 3 FLAIR study. Lancet HIV. 2021;8:e668\u201378. https:\/\/doi.org\/10.1016\/S2352-3018(21)00184-3.","journal-title":"Lancet HIV"},{"key":"2577_CR3","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1097\/QAD.0000000000002883","volume":"35","author":"AG Cutrell","year":"2021","unstructured":"Cutrell AG, Schapiro JM, Perno CF, et al. Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis. AIDS. 2021;35:1333\u201342. https:\/\/doi.org\/10.1097\/QAD.0000000000002883.","journal-title":"AIDS"},{"key":"2577_CR4","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1093\/JAC\/DKZ141","volume":"74","author":"N Neant","year":"2019","unstructured":"Neant N, Solas C, Bouazza N, et al. Concentration\u2013response model of rilpivirine in a cohort of HIV-1-infected Naive and pre-treated patients. J Antimicrob Chemother. 2019;74:1992\u20132002. https:\/\/doi.org\/10.1093\/JAC\/DKZ141.","journal-title":"J Antimicrob Chemother"},{"key":"2577_CR5","doi-asserted-by":"publisher","DOI":"10.1093\/CID\/CIAE475","author":"F Guti\u00e9rrez","year":"2024","unstructured":"Guti\u00e9rrez F, Fern\u00e1ndez-Gonz\u00e1lez M, Ledesma C, et al. Virological history predicts Non-sustained viral suppression with Long-Acting cabotegravir and rilpivirine therapy, independent of Pharmacokinetic parameters. Clin Infect Dis Published Online First: 19 September. 2024. https:\/\/doi.org\/10.1093\/CID\/CIAE475.","journal-title":"Clin Infect Dis Published Online First: 19 September"},{"key":"2577_CR6","doi-asserted-by":"publisher","unstructured":"Thoueille P, Saldanha SA, Schaller F, et al. Real-world trough concentrations and effectiveness of long-acting cabotegravir and rilpivirine: a multicenter prospective observational study in Switzerland. Lancet Reg Health Europe. 2023;36. https:\/\/doi.org\/10.1016\/J.LANEPE.2023.100793.","DOI":"10.1016\/J.LANEPE.2023.100793"},{"key":"2577_CR7","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1093\/CID\/CIAD370","volume":"77","author":"C Orkin","year":"2023","unstructured":"Orkin C, Schapiro JM, Perno CF, et al. Expanded multivariable models to assist patient selection for Long-Acting Cabotegravir\u2009+\u2009Rilpivirine treatment: clinical utility of a combination of patient, drug concentration, and viral factors associated with virologic failure. Clin Infect Dis. 2023;77:1423\u201331. https:\/\/doi.org\/10.1093\/CID\/CIAD370.","journal-title":"Clin Infect Dis"},{"key":"2577_CR8","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1111\/J.0006-341X.2003.00125.X","volume":"59","author":"B Rosner","year":"2003","unstructured":"Rosner B, Glynn RJ, Lee MLT. Incorporation of clustering effects for the Wilcoxon rank sum test: a large-sample approach. Biometrics. 2003;59:1089\u201398. https:\/\/doi.org\/10.1111\/J.0006-341X.2003.00125.X.","journal-title":"Biometrics"},{"key":"2577_CR9","doi-asserted-by":"publisher","DOI":"10.1093\/CID\/CIAE620","author":"SL Ford","year":"2025","unstructured":"Ford SL, Felizarta F, Han K, et al. Thigh injections of Cabotegravir\u2009+\u2009Rilpivirine in virally suppressed adults with human immunodeficiency virus type 1: A substudy of the phase 3b ATLAS-2\u00a0M study. Clin Infect Dis Published Online First: 29 January. 2025. https:\/\/doi.org\/10.1093\/CID\/CIAE620.","journal-title":"Clin Infect Dis Published Online First: 29 January"},{"key":"2577_CR10","doi-asserted-by":"publisher","first-page":"1994","DOI":"10.1016\/S0140-6736(20)32666-0","volume":"396","author":"ET Overton","year":"2021","unstructured":"Overton ET, Richmond G, Rizzardini G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2\u00a0M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet. 2021;396:1994\u20132005. https:\/\/doi.org\/10.1016\/S0140-6736(20)32666-0.","journal-title":"Lancet"},{"key":"2577_CR11","doi-asserted-by":"publisher","first-page":"e34","DOI":"10.1093\/INFDIS\/JIAD580","volume":"230","author":"ER Elliot","year":"2024","unstructured":"Elliot ER, Polli JW, Patel P, et al. Efficacy, safety, and pharmacokinetics by body mass index category in phase 3\/3b Long-Acting cabotegravir plus rilpivirine trials. J Infect Dis. 2024;230:e34\u201342. https:\/\/doi.org\/10.1093\/INFDIS\/JIAD580.","journal-title":"J Infect Dis"},{"key":"2577_CR12","doi-asserted-by":"publisher","first-page":"e679","DOI":"10.1016\/S2352-3018(21)00185-5","volume":"8","author":"H Jaeger","year":"2021","unstructured":"Jaeger H, Overton ET, Richmond G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2\u00a0M), 96-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet HIV. 2021;8:e679\u201389. https:\/\/doi.org\/10.1016\/S2352-3018(21)00185-5.","journal-title":"Lancet HIV"},{"key":"2577_CR13","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1093\/CID\/CIAE016","volume":"79","author":"BJ van Welzen","year":"2024","unstructured":"van Welzen BJ, Van Lelyveld SFL, Ter Beest G, et al. Virological failure after switch to Long-Acting cabotegravir and rilpivirine injectable therapy: an In-depth analysis. Clin Infect Dis. 2024;79:189\u201395. https:\/\/doi.org\/10.1093\/CID\/CIAE016.","journal-title":"Clin Infect Dis"},{"key":"2577_CR14","unstructured":"Bailon Alvarez L, Sabato S, Buhiichyk V, et al. Early virological failure with cabotegravir plus rilpivirine in clinical practice. HIV MEDICINE. WILEY 111 RIVER ST, HOBOKEN 07030\u2013\u20095774. NJ USA; 2023. p. 750."},{"key":"2577_CR15","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1097\/QAD.0000000000003887","volume":"38","author":"E Rubenstein","year":"2024","unstructured":"Rubenstein E, Diemer M, Goldwirt L, et al. Low cabotegravir trough concentrations without oral lead-in in patients with HIV-1 switching to long-acting cabotegravir and rilpivirine. Aids. 2024;38:1267\u20139.","journal-title":"Aids"},{"key":"2577_CR16","unstructured":"Seang S, Palacios C, Valin N, et al. HIV viremias among patients who discontinued cabotegravir (CAB)\/Rilpivirine (RPV) long acting (LA) intramuscular (IM) in reallife setting. HIV MEDICINE. WILEY 111 RIVER ST, HOBOKEN 07030\u2013\u20095774. NJ USA; 2023. pp. 150\u20131."},{"key":"2577_CR17","unstructured":"Ehret R, Kruedewagen B, Obermeier M. Cabotegravir\/Rilpivirin based long acting therapy with insufficient drug levels in routine drug monitoring. HIV MEDICINE. WILEY 111 RIVER ST, HOBOKEN 07030\u2013\u20095774. NJ USA; 2023. p. 481."},{"key":"2577_CR18","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1093\/JAC\/DKAE187","volume":"79","author":"M Mazzitelli","year":"2024","unstructured":"Mazzitelli M, Avolio A, Carandina R, Parisi S, Wensing A, Cattelan A. Characterization of a case of virological failure after switch to long-acting cabotegravir and rilpivirine. J Antimicrob Chemother. 2024;79:2074\u20136. https:\/\/doi.org\/10.1093\/JAC\/DKAE187.","journal-title":"J Antimicrob Chemother"},{"key":"2577_CR19","doi-asserted-by":"publisher","unstructured":"Gerstenberg J, Klinker H, Baier M, et al. Therapeutic drug monitoring of long acting rilpivirine and cabotegravir for treatment of HIV-1 Infection\u2013 A case series of five patients with one virologic failure after development of Two-Class resistance. Open Forum Infect Dis. 2024;11. https:\/\/doi.org\/10.1093\/OFID\/OFAE480.","DOI":"10.1093\/OFID\/OFAE480"}],"container-title":["Infection"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s15010-025-02577-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s15010-025-02577-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s15010-025-02577-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T08:53:00Z","timestamp":1764751980000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s15010-025-02577-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,4]]},"references-count":19,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["2577"],"URL":"https:\/\/doi.org\/10.1007\/s15010-025-02577-x","relation":{},"ISSN":["0300-8126","1439-0973"],"issn-type":[{"value":"0300-8126","type":"print"},{"value":"1439-0973","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,4]]},"assertion":[{"value":"13 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"SN, US, EW and CJO report personal fees from services for Gilead Sciences, MSD, and ViiV Healthcare \/ GSK, as well as educational support from Gilead Sciences and ViiV Healthcare.FS, AK, and CW report educational support from Gilead Sciences and ViiV Healthcare.AI does not report any conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}