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We investigated the potential of saquinavir (SQV), a protease inhibitor (PI) used in highly active antiretroviral therapy (HAART), as a candidate microbicide. SQV inhibited replication of clade B and clade C isolates in a dose-dependent manner in all cellular models tested: PM-1 CD4 T cells, peripheral blood mononuclear cells (PBMCs), monocyte-derived macrophages (MDMs), and immature monocyte-derived dendritic cells (iMDDCs). SQV also inhibited production of infectious virus in cervical, penile, and colorectal explants cocultured with T cells. Moreover, SQV demonstrated inhibitory potency against<jats:italic>trans<\/jats:italic>infection of T cells by<jats:italic>in vitro<\/jats:italic>-derived dendritic cells and by primary dendritic cells that emigrate from penile and cervical tissue explants. No cellular or tissue toxicity was detected in the presence of SQV, suggesting that this drug could be considered for development as a component of an effective microbicide, capable of blocking viral maturation and transmission of HIV-1 at mucosal surfaces.<\/jats:p>","DOI":"10.1128\/aac.00399-12","type":"journal-article","created":{"date-parts":[[2012,6,5]],"date-time":"2012-06-05T09:54:33Z","timestamp":1338890073000},"page":"4381-4390","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Saquinavir Inhibits Early Events Associated with Establishment of HIV-1 Infection: Potential Role for Protease Inhibitors in Prevention"],"prefix":"10.1128","volume":"56","author":[{"given":"Martha","family":"Stefanidou","sequence":"first","affiliation":[{"name":"Centre for Infection, Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Herrera","sequence":"additional","affiliation":[{"name":"Centre for Infection, Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Armanasco","sequence":"additional","affiliation":[{"name":"Centre for Infection, Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin J.","family":"Shattock","sequence":"additional","affiliation":[{"name":"Centre for Infection, Department of Cellular and Molecular Medicine, St. George's University of London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193748"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02051-08"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60202-5"},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1574-695X.2001.tb01588.x","article-title":"HIV protease inhibitors attenuate adherence of Candida albicans to epithelial cells in vitro","volume":"31","author":"Bektic J","year":"2001","unstructured":"BekticJ. 2001. 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