{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T17:09:34Z","timestamp":1773076174832,"version":"3.50.1"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI147384"],"award-info":[{"award-number":["AI147384"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,9,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The nucleos(t)ide analogs require phosphorylation to the pharmacologically active anabolites in cells. We investigated the hypothesis that single-nucleotide polymorphisms (SNPs) in genes that encode transporters and phosphodiesterase (PDE) enzymes involved in tenofovir (TFV), disoproxil fumarate (TDF), and lamivudine (3TC) disposition will be associated with concentrations of their phosphate anabolites and virologic response. Individuals with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection receiving TDF\/3TC-containing antiretroviral therapy were enrolled. Steady-state TFV diphosphate (TFV-DP) and 3TC triphosphate (3TC-TP) concentrations in peripheral blood mononuclear cells (PBMCs) and dried blood spot samples were quantified. The relationship between genetic variants and TFV-DP and 3TC-TP concentrations as well as with virologic response were examined using multivariable linear regression. Of the 136 participants (median age 43 years; 63% females), 6.6% had HBV non-suppression, and 7.4% had HIV non-suppression. The multidrug resistance protein 2 (encoded by\n              <jats:italic>ABCC2<\/jats:italic>\n              rs2273697) SNP was associated with 3TC-TP concentrations in PBMCs. The human organic anion transporter-1 (encoded by\n              <jats:italic>SLC28A2<\/jats:italic>\n              ) rs11854484 SNP was associated with HIV non-suppression, and when evaluated together with SNPs with marginal associations (\n              <jats:italic>ABCC2<\/jats:italic>\n              rs717620 and\n              <jats:italic>PDE1C<\/jats:italic>\n              rs30561), participants with two or three variants compared to those with none of these variants had an adjusted odds ratio of 48.3 (confidence interval, 4.3\u2013547.8) for HIV non-suppression. None of the SNPs were associated with HBV non-suppression. Our study identified\n              <jats:italic>ABCC2<\/jats:italic>\n              SNP to be associated with 3TC-TP concentrations in PBMCs. Also, a combination of genetic variants of drug transporters and PDE was associated with HIV non-suppression.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00549-24","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T13:01:25Z","timestamp":1722344485000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacogenetic determinants of tenofovir diphosphate and lamivudine triphosphate concentrations in people with HIV\/HBV coinfection"],"prefix":"10.1128","volume":"68","author":[{"given":"Jihyun","family":"Bae","sequence":"first","affiliation":[{"name":"Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa","family":"Tantawy","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Gong","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taimour","family":"Langaee","sequence":"additional","affiliation":[{"name":"Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Lartey","sequence":"additional","affiliation":[{"name":"Department of Medicine, Korle-Bu Teaching Hospital, Accra, Ghana"},{"name":"Department of Medicine and Therapeutics, University of Ghana Medical School, College of Health Sciences, University of Ghana, Accra, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Ganu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Korle-Bu Teaching Hospital, Accra, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Tachi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Korle-Bu Teaching Hospital, Accra, Ghana"},{"name":"Department of Medicine and Therapeutics, University of Ghana Medical School, College of Health Sciences, University of Ghana, Accra, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oluwayemisi","family":"Ojewale","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and Global Medicine, University of Florida, Gainesville, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adjoa","family":"Obo-Akwa","sequence":"additional","affiliation":[{"name":"Department of Medicine, Korle-Bu Teaching Hospital, Accra, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isaac","family":"Boamah","sequence":"additional","affiliation":[{"name":"Department of Medicine, Korle-Bu Teaching Hospital, Accra, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lane R.","family":"Bushman","sequence":"additional","affiliation":[{"name":"Colorado Antiviral Pharmacology Laboratory and Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas","family":"Ellison","sequence":"additional","affiliation":[{"name":"Colorado Antiviral Pharmacology Laboratory and Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, 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