{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T02:11:14Z","timestamp":1776219074855,"version":"3.50.1"},"reference-count":72,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Preexposure prophylaxis (PrEP) using antiretroviral drugs is effective in reducing the risk of human immunodeficiency virus type 1 (HIV-1) infection, but adherence to the PrEP regimen is needed. To improve adherence, a long-acting injectable formulation of the nonnucleoside reverse transcriptase (RT) inhibitor rilpivirine (RPV LA) has been developed. However, there are concerns that PrEP may select for drug-resistant mutations during preexisting or breakthrough infections, which could promote the spread of drug resistance and limit options for antiretroviral therapy. To address this concern, we administered RPV LA to macaques infected with simian immunodeficiency virus containing HIV-1 RT (RT-SHIV). Peak plasma RPV levels were equivalent to those reported in human trials and waned over time after dosing. RPV LA resulted in a 2-log decrease in plasma viremia, and the therapeutic effect was maintained for 15 weeks, until plasma drug concentrations dropped below 25 ng\/ml. RT mutations E138G and E138Q were detected in single clones from plasma virus in separate animals only at one time point, and no resistance mutations were detected in viral RNA isolated from tissues. Wild-type and E138Q RT-SHIV displayed similar RPV susceptibilities<jats:italic>in vitro<\/jats:italic>, whereas E138G conferred 2-fold resistance to RPV. Overall, selection of RPV-resistant variants was rare in an RT-SHIV macaque model despite prolonged exposure to slowly decreasing RPV concentrations following injection of RPV LA.<\/jats:p>","DOI":"10.1128\/aac.01937-15","type":"journal-article","created":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T02:28:33Z","timestamp":1444098513000},"page":"7762-7770","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse Transcriptase"],"prefix":"10.1128","volume":"59","author":[{"given":"Kevin","family":"Melody","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"McBeth","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Kline","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela D. M.","family":"Kashuba","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John W.","family":"Mellors","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zandrea","family":"Ambrose","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Global update on the health sector response to HIV, 2014","author":"WHO","year":"2014","unstructured":"WHO. 2014. Global update on the health sector response to HIV, 2014. WHO, Geneva, Switzerland."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61127-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1108524"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011205"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110711"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1202614"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193748"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000172"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050028"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050632"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3000391"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000169"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000160"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.4088\/JCP.13065su1c.07","article-title":"Patient outcomes within schizophrenia treatment: a look at the role of long-acting injectable antipsychotics","volume":"75","author":"Bera RB","year":"2014","unstructured":"Bera RB. 2014. Patient outcomes within schizophrenia treatment: a look at the role of long-acting injectable antipsychotics. J Clin Psychiatry 75(Suppl 2):S30\u2013S33.","journal-title":"J Clin Psychiatry"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1111\/j.1365-2265.2009.03744.x","article-title":"Randomized cross-over clinical trial of injectable vs. implantable depot testosterone for maintenance of testosterone replacement therapy in androgen deficient men","volume":"73","author":"Fennell C","year":"2010","unstructured":"Fennell C, Sartorius G, Ly LP, Turner L, Liu PY, Conway AJ, Handelsman DJ. 2010. Randomized cross-over clinical trial of injectable vs. implantable depot testosterone for maintenance of testosterone replacement therapy in androgen deficient men. Clin Endocrinol (Oxf) 73:102\u2013109.","journal-title":"Clin Endocrinol (Oxf)"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2010.04.013"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110855"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32835cee6e"},{"key":"e_1_3_2_20_2","volume-title":"Edurant package insert","author":"Janssen Therapeutics","year":"2011","unstructured":"Janssen Therapeutics. 2011. Edurant package insert. Janssen Therapeutics, Titusville, NJ."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31823df4da"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01529-09"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2014.118"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000365"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.12247"},{"key":"e_1_3_2_26_2","first-page":"642","article-title":"2014 update of the drug resistance mutations in HIV-1","volume":"22","author":"Wensing AM","year":"2014","unstructured":"Wensing AM, Calvez V, Gunthard HF, Johnson VA, Paredes R, Pillay D, Shafer RW, Richman DD. 2014. 2014 update of the drug resistance mutations in HIV-1. Top Antivir Med 22:642\u2013650.","journal-title":"Top Antivir Med"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000102"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu677"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu233"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.24.13553-13561.2004"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01301-07"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1890"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.18.8210"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/jmp.12126"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.9.3483-3490.2004"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2010.06.008"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2012.0080"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0684.2009.00374.x"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-6405-6-23"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089300"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01701-10"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015835"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.12.7349-7354.2005"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02356-09"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-6-101"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02422-10"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003936"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003162"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086997"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.18.8358-8367.2000"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.9.6988-6996.1998"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.12.2781"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.4.2232-2239.1992"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0684.2005.00128.x"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084275"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00986-09"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm040840e"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02114-13"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1086\/656722"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10461-014-0751-x"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402269"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570162X11311020005"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01963-12"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.11.4999-5008.2001"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-9-99"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32835d9f6d"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001810"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2014.5127.abstract"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1179\/1528433614Z.0000000009"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2006.05392.x"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31823aca74"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01029-13"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00348-13"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01937-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01937-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T15:35:02Z","timestamp":1718120102000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01937-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12]]},"references-count":72,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1128\/AAC.01937-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.01937-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12]]},"assertion":[{"value":"2015-08-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-09-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-11-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}