{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T17:26:10Z","timestamp":1768325170911,"version":"3.49.0"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1019228"],"award-info":[{"award-number":["OPP1019228"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>A vaginal ring containing dapivirine (DPV) has shown moderate protective efficacy against HIV-1 acquisition, but the activity of DPV against efavirenz (EFV)- and nevirapine (NVP)-resistant viruses that could be transmitted is not well defined. We investigated DPV cross-resistance of subtype C HIV-1 from individuals on failing NVP- or EFV-containing antiretroviral therapy (ART) in South Africa. Plasma samples were obtained from individuals with &gt;10,000 copies of HIV RNA\/ml and with HIV-1 containing at least one non-nucleoside reverse transcriptase (NNRTI) mutation. Susceptibility to NVP, EFV, and DPV in TZM-bl cells was determined for recombinant HIV-1<jats:sub>LAI<\/jats:sub>containing bulk-amplified, plasma-derived, full-length reverse transcriptase sequences. Fold change (FC) values were calculated compared with a composite 50% inhibitory concentration (IC<jats:sub>50<\/jats:sub>) from 12 recombinant subtype C HIV-1<jats:sub>LAI<\/jats:sub>plasma-derived viruses from treatment-naive individuals in South Africa. A total of 25\/100 (25%) samples showed &gt;500-FCs to DPV compared to treatment-naive samples with IC<jats:sub>50<\/jats:sub>s exceeding the maximum DPV concentration tested (132 ng\/ml). A total of 66\/100 (66%) samples displayed 3- to 306-FCs, with a median IC<jats:sub>50<\/jats:sub>of 17.6 ng\/ml. Only 9\/100 (9%) samples were susceptible to DPV (FC &lt; 3). Mutations L100I and K103N were significantly more frequent in samples with &gt;500-fold resistance to DPV compared to samples with a \u2264500-fold resistance. A total of 91% of samples with NNRTI-resistant HIV-1 from individuals on failing first-line ART in South Africa exhibited \u22653-fold cross-resistance to DPV. This level of resistance exceeds expected plasma concentrations, but very high genital tract DPV concentrations from DPV ring use could block viral replication. It is critically important to assess the frequency of transmitted and selected DPV resistance in individuals using the DPV ring.<\/jats:p>","DOI":"10.1128\/aac.01805-16","type":"journal-article","created":{"date-parts":[[2016,11,29]],"date-time":"2016-11-29T02:31:07Z","timestamp":1480386667000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Frequent Cross-Resistance to Dapivirine in HIV-1 Subtype C-Infected Individuals after First-Line Antiretroviral Therapy Failure in South Africa"],"prefix":"10.1128","volume":"61","author":[{"given":"Kerri J.","family":"Penrose","sequence":"first","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole L.","family":"Wallis","sequence":"additional","affiliation":[{"name":"BARC-SA and Lancet Laboratories, Johannesburg, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chanson J.","family":"Brumme","sequence":"additional","affiliation":[{"name":"BC Centre for Excellence in HIV\/AIDS, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen A.","family":"Hamanishi","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelley C.","family":"Gordon","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel V.","family":"Viana","sequence":"additional","affiliation":[{"name":"BARC-SA and Lancet Laboratories, Johannesburg, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. Richard","family":"Harrigan","sequence":"additional","affiliation":[{"name":"BC Centre for Excellence in HIV\/AIDS, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John W.","family":"Mellors","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urvi M.","family":"Parikh","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10461-012-0215-0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2013.09.025"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128857"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506110"},{"key":"e_1_3_3_6_2","volume-title":"Conference on Retroviruses and Opportunistic Infections","author":"Nel A","year":"2016","unstructured":"Nel A KapigaS BekkerLG DevlinB BorremansM RosenbergZ. 2016. Safety and efficacy of dapivirine vaginal ring for HIV-1 prevention in African women, abstr 110LB. Conference on Retroviruses and Opportunistic Infections, Boston, MA. http:\/\/www.croiconference.org\/sessions\/safety-and-efficacy-dapivirine-vaginal-ring-hiv-1-prevention-african-women."},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/v6082960"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05821-11"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01156-08"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis501"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir385"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku214"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02904-13"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-7291-9_13"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1159\/000331998"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000280"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000702"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00986-09"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/v6104095"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01536-13"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04215-14"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.13.6836-6840.2002"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.133"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.12.2781"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01937-15"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2009.11.011"},{"key":"e_1_3_3_27_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini YaH Yosef","year":"1995","unstructured":"Benjamini YaHYosef . 1995. 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