{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:24:25Z","timestamp":1787736265268,"version":"build-2784847793"},"reference-count":67,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Gates Foundation","doi-asserted-by":"publisher","award":["INV-030801"],"award-info":[{"award-number":["INV-030801"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"award":["INV-030801"],"award-info":[{"award-number":["INV-030801"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Multipurpose prevention technologies (MPTs) that combine protection against HIV and unintended pregnancy can improve women\u2019s health outcomes by simplifying use and enhancing adherence. We developed a long-acting (LA) implant for the simultaneous and sustained delivery of the antiretroviral islatravir (ISL) and the contraceptive hormone etonogestrel (ENG). Methods: Using extruded poly-\u03b5-caprolactone (PCL) tubing, reservoir-style implants were fabricated and evaluated in three configurations: (Group 1) a two-segment implant formed by joining separate ISL- and ENG-containing tubes; (Group 2) a single tube divided into two drug compartments by a heat-sealed PCL spacer; (Group 3) separate single-drug implants. In vitro release was assessed in phosphate-buffered saline at 37 \u00b0C, and safety and pharmacokinetic (PK) profiles were evaluated in New Zealand White rabbits (n = 4\/group) over approximately 90 days. Results: The average ISL daily in vitro release rates for Groups 1, 2, and 3 were 29 \u00b1 5 \u00b5g\/day, 18 \u00b1 5 \u00b5g\/day, and 47 \u00b1 8 \u00b5g\/day, respectively, and ENG daily in vitro release rates were 39 \u00b1 9 \u00b5g\/day, 41 \u00b1 8 \u00b5g\/day, and 33 \u00b1 7 \u00b5g\/day. From day 28 through the end of the study, median (IQR) plasma concentrations were 0.22 (0.18\u20130.27) ng\/mL, 0.28 (0.24\u20130.33) ng\/mL, and 0.31 (0.28\u20130.33) ng\/mL for ISL in Groups 1, 2, and 3, respectively, and 0.26 (0.21\u20130.31) ng\/mL, 0.25 (0.16\u20130.47) ng\/mL, and 0.30 (0.23\u20130.38) ng\/mL for ENG in Groups 1, 2 and 3, respectively. Implants across all groups were well tolerated and demonstrated favorable local tolerability over the 90-day dosing period. Conclusions: Integration of multiple indications into a single platform capable of sustained release over an extended duration holds potential to address persistent gaps in women\u2019s sexual and reproductive health needs.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091060","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:05:46Z","timestamp":1787735146000},"page":"1060","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and Preclinical Evaluation of a Dual-Drug Implant for Long-Acting HIV Prevention and Contraception"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1546-9955","authenticated-orcid":false,"given":"Archana","family":"Krovi","sequence":"first","affiliation":[{"name":"RTI International, 3040 E. Cornwallis Road, Research Triangle Park, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6293-5489","authenticated-orcid":false,"given":"Leanna","family":"Levin","sequence":"additional","affiliation":[{"name":"RTI International, 3040 E. Cornwallis Road, Research Triangle Park, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg J.","family":"Gatto","sequence":"additional","affiliation":[{"name":"RTI International, 3040 E. Cornwallis Road, Research Triangle Park, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1509-5092","authenticated-orcid":false,"given":"Ellen H.","family":"Luecke","sequence":"additional","affiliation":[{"name":"RTI International, 3040 E. Cornwallis Road, Research Triangle Park, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3963-6909","authenticated-orcid":false,"given":"Rhonda","family":"Brand","sequence":"additional","affiliation":[{"name":"Department of Medicine and Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Swistok","sequence":"additional","affiliation":[{"name":"Department of Medicine and Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0291-5111","authenticated-orcid":false,"given":"Mackenzie L.","family":"Cottrell","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7026-7224","authenticated-orcid":false,"given":"Amanda P.","family":"Schauer","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah M.","family":"Johnson","sequence":"additional","affiliation":[{"name":"RTI International, 3040 E. Cornwallis Road, Research Triangle Park, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Holt, B.Y., van der Straten, A., Barker, T., Chirenje, Z.M., Cameron, A.-I., Scott, C., Casas, C.P., and Romano, J. (2023). Strategic actions to advance multipurpose prevention technologies in low- and middle-income countries. Front. Reprod. Health, 5.","DOI":"10.3389\/frph.2023.1150857"},{"key":"ref_2","unstructured":"(2025, December 03). Unintended Pregnancy and Abortion Worldwide|Guttmacher Institute. Available online: https:\/\/www.guttmacher.org\/fact-sheet\/induced-abortion-worldwide."},{"key":"ref_3","unstructured":"(2025, December 03). Global HIV & AIDS Statistics\u2014Fact Sheet|UNAIDS. 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