{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:39:32Z","timestamp":1787009972078,"version":"build-2736575974"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:p>\n                    In Advancing Clinical Therapeutics Globally protocol A5372, a pharmacokinetic study of dolutegravir with 1-month of daily rifapentine\/isoniazid, twice-daily dolutegravir offset the induction effects of rifapentine on plasma dolutegravir trough concentrations (C\n                    <jats:sub>trough<\/jats:sub>\n                    ). Here, we characterize the impact on dolutegravir C\n                    <jats:sub>trough<\/jats:sub>\n                    of\n                    <jats:italic toggle=\"yes\">UGT1A1<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">AADAC<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">NAT2<\/jats:italic>\n                    polymorphisms that affect dolutegravir, rifapentine, and isoniazid, respectively. People with HIV receiving dolutegravir-based antiretroviral therapy with an indication to treat latent tuberculosis underwent pharmacokinetic sampling during dolutegravir 50\u2005mg once daily alone, and on day 28 of dolutegravir 50\u2005mg twice daily with rifapentine\/isoniazid. Multivariable linear regression models characterized genetic associations with dolutegravir C\n                    <jats:sub>trough<\/jats:sub>\n                    . Among 30 participants evaluable for genetic associations, median (Q1, Q3) day 0 dolutegravir C\n                    <jats:sub>trough<\/jats:sub>\n                    was 1745 (1099, 2694) ng\/ml, and day 28 was 2146 (1412, 2484) ng\/ml. Day 28 C\n                    <jats:sub>trough<\/jats:sub>\n                    was higher with\n                    <jats:italic toggle=\"yes\">UGT1A1<\/jats:italic>\n                    rs887829 TT [geometric mean ratio (GMR)\u2005=\u20051.65; 90% confidence interval (CI): 0.97\u20132.78] and CT (GMR\u2005=\u20051.38; 90% CI: 1.02\u20131.86) than with CC, and was higher with\n                    <jats:italic toggle=\"yes\">AADAC<\/jats:italic>\n                    rs1803155 GG (GMR\u2005=\u20051.79; 90% CI: 1.09\u20132.93) and AG (GMR\u2005=\u20051.48; 90% CI: 1.14\u20131.90) than with AA. Median day 28 C\n                    <jats:sub>trough<\/jats:sub>\n                    ranged from 1205 (1063, 1897) ng\/ml with 4 total\n                    <jats:italic toggle=\"yes\">UGT1A1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">AADAC<\/jats:italic>\n                    risk alleles, to 3882 and 3717\u2009ng\/ml with only one risk allele. Individuals with concomitant\n                    <jats:italic toggle=\"yes\">AADAC<\/jats:italic>\n                    slow metabolizer and\n                    <jats:italic toggle=\"yes\">UGT1A1<\/jats:italic>\n                    normal metabolizer genotypes may be at greater risk for clinically significant drug\u2013drug interactions between rifapentine\/isoniazid and dolutegravir.\n                  <\/jats:p>","DOI":"10.1097\/fpc.0000000000000562","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T13:00:06Z","timestamp":1739797206000},"page":"140-144","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacogenetics of plasma dolutegravir exposure during 1-month rifapentine\/isoniazid treatment of latent tuberculosis"],"prefix":"10.1097","volume":"35","author":[{"given":"Nia","family":"Covington","sequence":"first","affiliation":[{"name":"College of Charleston, Charleston, South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne F.","family":"Luetkemeyer","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie Z.","family":"Imperial","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney","family":"Dawson","sequence":"additional","affiliation":[{"name":"University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoninah","family":"Cramer","sequence":"additional","affiliation":[{"name":"Frontier Science Foundation, Brookline, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Rosenkranz","sequence":"additional","affiliation":[{"name":"Frontier Science Foundation, Brookline, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Swindells","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center, Omaha, Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Gelmanova","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anchalee","family":"Avihingsanon","sequence":"additional","affiliation":[{"name":"Thai Red Cross AIDS Research Centre, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto C.","family":"Arduino","sequence":"additional","affiliation":[{"name":"McGovern Medical School at UTHealth, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wadzanai","family":"Samaneka","sequence":"additional","affiliation":[{"name":"University of Zimbabwe, Harare, Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly E.","family":"Dooley","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rada","family":"Savic","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony T.","family":"Podany","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center, Omaha, Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Haas","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center"},{"name":"Meharry Medical College, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"R1-20250430","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1056\/NEJM199902043400507","article-title":"Tuberculosis in patients with human immunodeficiency virus infection.","volume":"340","author":"Havlir","year":"1999","journal-title":"N Engl J Med"},{"key":"R2-20250430","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1056\/NEJMra1405427","article-title":"Latent Mycobacterium tuberculosis infection.","volume":"372","author":"Getahun","year":"2015","journal-title":"N Engl J Med"},{"key":"R3-20250430","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1056\/NEJMoa1806808","article-title":"One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis.","volume":"380","author":"Swindells","year":"2019","journal-title":"N Engl J 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exposure among Southern Africans living with HIV.","volume":"226","author":"Cindi","year":"2022","journal-title":"J Infect Dis"},{"key":"R9-20250430","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1093\/jac\/dkaa490","article-title":"Decreased plasma rifapentine concentrations associated with AADAC single nucleotide polymorphism in adults with tuberculosis.","volume":"76","author":"Weiner","year":"2021","journal-title":"J Antimicrob Chemother"},{"key":"R10-20250430","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1053\/jhep.2002.32102","article-title":"Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis.","volume":"35","author":"Huang","year":"2002","journal-title":"Hepatology"},{"key":"R11-20250430","doi-asserted-by":"crossref","first-page":"311","DOI":"10.2217\/14622416.9.3.311","article-title":"Pharmacogenomics of anti-TB drugs-related hepatotoxicity.","volume":"9","author":"Roy","year":"2008","journal-title":"Pharmacogenomics"},{"key":"R12-20250430","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1097\/QAD.0b013e32834a1dd9","article-title":"Antiviral activity, safety, and pharmacokinetics\/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults.","volume":"25","author":"Min","year":"2011","journal-title":"AIDS"},{"key":"R13-20250430","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s40262-013-0093-2","article-title":"Clinical pharmacokinetic, pharmacodynamic and drug-interaction profile of the integrase inhibitor dolutegravir.","volume":"52","author":"Cottrell","year":"2013","journal-title":"Clin Pharmacokinet"},{"key":"R14-20250430","first-page":"983","article-title":"Twice-daily dolutegravir based antiretroviral therapy with one month of daily rifapentine and isoniazid (1HP) for TB prevention.","volume":"79","author":"Podany","year":"2024","journal-title":"Clin Infect Dis"},{"key":"R15-20250430","first-page":"126","article-title":"Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis.","volume":"33","author":"Agyemang","year":"2023","journal-title":"Pharmacogenet Genomics"},{"key":"R16-20250430","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1186\/s12879-017-2717-x","article-title":"Impact of UGT1A1 gene polymorphisms on plasma dolutegravir trough concentrations and neuropsychiatric adverse events in Japanese individuals infected with HIV-1.","volume":"17","author":"Yagura","year":"2017","journal-title":"BMC Infect Dis"},{"key":"R17-20250430","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/cpt.269","article-title":"Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for UGT1A1 and atazanavir prescribing.","volume":"99","author":"Gammal","year":"2016","journal-title":"Clin Pharmacol 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Chemother"}],"container-title":["Pharmacogenetics and Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/FPC.0000000000000562","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T07:00:30Z","timestamp":1745996430000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/FPC.0000000000000562"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,12]]},"references-count":19,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.1097\/fpc.0000000000000562","relation":{},"ISSN":["1744-6872","1744-6880"],"issn-type":[{"value":"1744-6872","type":"print"},{"value":"1744-6880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,12]]}}}