{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T06:21:43Z","timestamp":1790490103698,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health","award":["R01-AI124965"],"award-info":[{"award-number":["R01-AI124965"]}]},{"DOI":"10.13039\/100000025","name":"NIMH","doi-asserted-by":"publisher","award":["P30 MH062261"],"award-info":[{"award-number":["P30 MH062261"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nebraska Research Initiative (NRI) Collaborative"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Multiple tissue reservoirs are established soon after HIV infection, and some tissues may also be pharmacological sanctuaries. Parenteral administration of antiretroviral (ARV) drugs for treatment and prevention of HIV infection is an active area of drug development. The influence of route of administration on ARV tissue pharmacokinetics is not known.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To investigate ARV pharmacokinetics in lymphatic and select non-lymphatic tissues (e.g. brain and testes) after intramuscular and subcutaneous administration compared with oral in BALB\/c mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Tissue concentrations of cobicistat, efavirenz, elvitegravir, maraviroc, rilpivirine, tenofovir alafenamide and tenofovir disoproxil fumarate were determined. The tissue penetration ratio (TPR) was the primary measure for comparison; a change in TPR arises from factors affecting tissue distribution controlling for changes in systemic bioavailability.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Intramuscular and subcutaneous delivery increased TPRs in the lymph node and spleen for 27 of 28 (96%) drug administration events. Decreased TPRs, however, were found in some tissues such as the brain and testes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These results demonstrate a change in route of drug administration from oral to intramuscular or subcutaneous can change tissue uptake. This has implications for HIV pharmacotherapy. For example, HIV persists in lymphoid tissues despite long-term oral ARV therapy, and low ARV concentrations have been found in lymphoid tissues. The improved ARV lymphatic tissue bioavailability with intramuscular and subcutaneous administration allows future studies to investigate these routes of drug administration as a therapeutic manoeuvre to limit viral persistence and eliminate viral sanctuaries in the lymphatic tissues, which is a prerequisite for eradication of HIV.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab228","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T19:11:22Z","timestamp":1624302682000},"page":"2651-2658","source":"Crossref","is-referenced-by-count":21,"title":["Intramuscular and subcutaneous administration of antiretroviral drugs, compared with oral, enhances delivery to lymphoid tissues in BALB\/c mice"],"prefix":"10.1093","volume":"76","author":[{"given":"Shetty Ravi","family":"Dyavar","sequence":"first","affiliation":[{"name":"Antiviral Pharmacology Laboratory, Center for Drug Discovery, University of Nebraska Medical Center (UNMC), Omaha, NE, 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