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Type I interferons (IFN) mediate antiviral effects through different mechanisms than cART. We previously showed that IFN\u03b114 is the most potent IFN\u03b1 subtype against HIV-1 and that it can significantly reduce the HIV-1 proviral reservoir. This study sought to determine whether combining cART with IFN\u03b114 therapy would produce greater reductions in HIV-1 viral and proviral loads than ART alone. Immunodeficient <jats:italic>Rag2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup><jats:italic>\u03b3<\/jats:italic><jats:sub><jats:italic>c<\/jats:italic><\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup><jats:italic>CD47<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> C57BL\/6 mice were humanized by the BLT method, infected with HIV-1<jats:sub>JR-CSF<\/jats:sub> and the <jats:italic>in vivo<\/jats:italic> efficacy of cART was compared with combined cART\/IFN\u03b114 therapy. Infection was allowed to establish for 6 weeks prior to 4 weeks of treatment with oral cART either with or without IFN\u03b114. Plasma viral RNA and splenic CD4<jats:sup>+<\/jats:sup> T cell viral DNA levels were measured immediately after treatment and after 2 weeks of therapy interruption. Augmentation of cART with IFN\u03b114 resulted in significantly enhanced suppression of HIV-1 plasma viremia. However, no significant reduction in total viral DNA was detectable. Furthermore, virus rebounded after treatment interruption to similar levels in both groups. Thus, augmentation of cART with IFN\u03b114 resulted in a more pronounced reduction of HIV viremia levels over cART alone, but the effect was not potent enough to be detected at the viral DNA level or to prevent virus rebound following therapy interruption in immune system-humanized mice.<\/jats:p>","DOI":"10.1038\/s41598-019-54650-9","type":"journal-article","created":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T11:37:14Z","timestamp":1575286634000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Concurrent administration of IFN\u03b114 and cART in TKO-BLT mice enhances suppression of HIV-1 viremia but does not eliminate the latent reservoir"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6397-6551","authenticated-orcid":false,"given":"Kathrin","family":"Sutter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5329-4546","authenticated-orcid":false,"given":"Kerry J.","family":"Lavender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Messer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Widera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent","family":"Race","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim J.","family":"Hasenkrug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Dittmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,2]]},"reference":[{"key":"54650_CR1","doi-asserted-by":"publisher","first-page":"4013","DOI":"10.1182\/blood-2013-06-506949","volume":"122","author":"KJ Lavender","year":"2013","unstructured":"Lavender, K. 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