{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T18:14:48Z","timestamp":1771352088683,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The emergence and spread of human immunodeficiency virus (HIV) drug-resistant strains present a major barrier to effective lifelong antiretroviral therapy. The anticipated rise in long-acting subcutaneous lenacapavir (LEN) use, along with the increased risk of transmitted resistance and pre-exposure prophylaxis\u2013associated resistance, underscore the urgent need for advanced genotyping methods to enhance clinical care and prevention strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed the portable HIV genotyping (PHG) platform, which combines cost-effective next-generation sequencing with cloud computing to screen for resistance to 28 antiretroviral drugs across 5 major classes, including LEN. We analyzed 3 study cohorts and compared our drug-resistance findings with standard-care testing results and high-fidelity sequencing data obtained through unique molecular identifier (UMI) labeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PHG identified 2 major LEN-resistance mutations in 1 participant, confirmed by an additional independent sequencing run. Across 3 study cohorts, PHG consistently detected the same drug-resistance mutations as standard-care genotyping and high-fidelity UMI labeling in most tested specimens. PHG's 10% limit of detection minimized false-positive results and enabled identification of minority variants with less than 20% frequency, pointing to underdiagnosis of drug resistance in clinical care. Furthermore, PHG identified linked cross-class resistance mutations, confirmed by UMI labeling, including linked cross-resistance in a participant who reported use of long-acting cabotegravir and rilpivirine. We also observed multiyear persistence of linked cross-class resistance mutations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PHG demonstrates significant improvements over standard-care HIV genotyping, offering deeper insights into LEN resistance, minority variants, and cross-class resistance using a low-cost, high-throughput portable sequencing technology and publicly available cloud computing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaf458","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T11:53:30Z","timestamp":1755258810000},"page":"e360-e369","source":"Crossref","is-referenced-by-count":1,"title":["Design and Evaluation of Next-Generation HIV Genotyping for Detection of Resistance Mutations to 28 Antiretroviral Drugs Across 5 Major Classes Including Lenacapavir"],"prefix":"10.1093","volume":"81","author":[{"given":"Sung Yong","family":"Park","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California , Los Angeles, California ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Takayama","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Keck School of Medicine, University of Southern California , Los Angeles, California ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenica","family":"Ryu","sequence":"additional","affiliation":[{"name":"Rand Schrader Clinic, Los Angeles General Medical Center , Los Angeles, California ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Sattah","sequence":"additional","affiliation":[{"name":"Rand Schrader Clinic, Los Angeles General Medical 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