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Given subtype C represents around half of all HIV-1 infections globally, we examined PI susceptibility in subtype C viruses from treatment-na\u00efve individuals. PI susceptibility was measured in a single round infection assay of full-length, replication competent MJ4\/<jats:italic>gag<\/jats:italic> chimeric viruses, encoding the <jats:italic>gag<\/jats:italic> gene and 142 nucleotides of <jats:italic>pro<\/jats:italic> derived from viruses in 20 patients in the Zambia-Emory HIV Research Project acute infection cohort. Ten-fold variation in susceptibility to PIs atazanavir and lopinavir was observed across 20 viruses, with EC<jats:sub>50<\/jats:sub>s ranging 0.71\u20136.95\u2009nM for atazanvir and 0.64\u20138.54\u2009nM for lopinavir. Ten amino acid residues in Gag correlated with lopinavir EC<jats:sub>50<\/jats:sub> (p\u2009&lt;\u20090.01), of which 380\u2009K and 389I showed modest impacts on <jats:italic>in vitro<\/jats:italic> drug susceptibility. Finally a significant relationship between drug susceptibility and replication capacity was observed for atazanavir and lopinavir but not darunavir. Our findings demonstrate large variation in susceptibility of PI-na\u00efve subtype C viruses that appears to correlate with replication efficiency and could impact clinical outcomes.<\/jats:p>","DOI":"10.1038\/srep38153","type":"journal-article","created":{"date-parts":[[2016,11,30]],"date-time":"2016-11-30T10:39:30Z","timestamp":1480502370000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Wide variation in susceptibility of transmitted\/founder HIV-1 subtype C Isolates to protease inhibitors and association with in vitro replication efficiency"],"prefix":"10.1038","volume":"6","author":[{"given":"Katherine A.","family":"Sutherland","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dami A.","family":"Collier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel T.","family":"Claiborne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica L.","family":"Prince","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin J.","family":"Deymier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravindra K.","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,11,30]]},"reference":[{"key":"BFsrep38153_CR1","unstructured":"WHO. 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