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In a quest to reduce lifelong drug exposure and minimize or avoid the toxicity of NRTI<\/jats:styled-content>s, \u201cNRTI<\/jats:styled-content>\u2010reducing\u201d regimens have been investigated. This descriptive review assessing the results of NRTI<\/jats:styled-content>\u2010reducing strategies from the largest randomized trials focuses on virological efficacy, resistance, regimen safety (in terms of bone mineral density, renal function, lipids and central nervous system function) and simplicity. The review considers efficacy across various NRTI<\/jats:styled-content>\u2010sparing strategies, for example an integrase strand transfer inhibitor (INSTI<\/jats:styled-content>) plus a ritonavir\u2010boosted protease inhibitor (PI<\/jats:styled-content>\/r) or PI<\/jats:styled-content>\/r + lamivudine (3TC<\/jats:styled-content>), in both na\u00efve and switch regimes. Of 10 key studies in treatment\u2010na\u00efve adults assessing five NRTI<\/jats:styled-content>\u2010reducing strategies, only four studies demonstrated noninferiority vs<\/jats:italic>. SOC<\/jats:styled-content> [GARDEL<\/jats:styled-content>, NEAT<\/jats:styled-content> 001, AIDS<\/jats:styled-content> Clinical Trials Group 5142 and PROGRESS<\/jats:styled-content>]. In switch settings, 17 studies (10 randomized) were reviewed that used four strategies, including three studies assessing an INSTI<\/jats:styled-content> plus a nonnucleoside reverse transcriptase inhibitor . Noninferiority of the NRTI<\/jats:styled-content>\u2010reducing arm was shown in six of 10 studies (ATLAS<\/jats:styled-content>\u2010M, SALT<\/jats:styled-content>, DUAL<\/jats:styled-content>, OLE<\/jats:styled-content>, LATTE<\/jats:styled-content>\u20102 and SWORD<\/jats:styled-content>). In general, NRTI<\/jats:styled-content>\u2010reducing therapy did not always result in an improvement in short\u2010 or long\u2010term adverse events; however, in many cases, these endpoints were not reported. Some of these studies reported higher virological failure rates with more frequent emergence of resistance mutations. None of these NRTI<\/jats:styled-content>\u2010reducing strategies has been compared against a single\u2010pill regimen, including those containing tenofovir alafenamide. Only strategies demonstrating noninferior efficacy, a benefit in safety\/tolerability, and a favourable cost\u2010efficacy ratio, preferably in a single pill, will eventually match the current SOC<\/jats:styled-content> of triple ARV<\/jats:styled-content> therapy.<\/jats:p>","DOI":"10.1111\/hiv.12534","type":"journal-article","created":{"date-parts":[[2017,7,24]],"date-time":"2017-07-24T10:08:37Z","timestamp":1500890917000},"page":"18-32","source":"Crossref","is-referenced-by-count":36,"title":["Nucleoside reverse transcriptase inhibitor\u2010reducing strategies in HIV treatment: assessing the evidence"],"prefix":"10.1111","volume":"19","author":[{"given":"C","family":"Orkin","sequence":"first","affiliation":[{"name":"Infection and Immunity Barts Health NHS Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JM","family":"Llibre","sequence":"additional","affiliation":[{"name":"University Hospital Germans Trias i Pujol Infectious Diseases and \u201cFight AIDS\u201d Foundation Badalona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Gallien","sequence":"additional","affiliation":[{"name":"Immunology and Infectious Diseases Henri Mondor Hospital Paris Est Cr\u00e9teil University Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Antinori","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Department National Institute for Infectious Diseases \u201cLazzaro Spallanzani\u201d Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GMN","family":"Behrens","sequence":"additional","affiliation":[{"name":"Department for Clinical Immunology and Rheumatology Hannover Medical School Hannover Germany"},{"name":"German Center for Infection Research St Vincent's Hospital Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Carr","sequence":"additional","affiliation":[{"name":"Centre for Applied Medical Research St Vincent's Hospital Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000243"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61113-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32833a3946"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081355"},{"key":"e_1_2_7_6_1","unstructured":"EACS.EACS Guidelines Version 8.0.http:\/\/wwweacsocietyorg\/guidelines\/eacs-guidelines\/eacs-guidelineshtml2015."},{"key":"e_1_2_7_7_1","first-page":"1","article-title":"Going beyond undetectable: a review of the unmet long\u2010term health needs of people living with HIV","volume":"1","author":"Aguiar C","year":"2015","journal-title":"Key Opin Med"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60616-X"},{"key":"e_1_2_7_9_1","unstructured":"KityoC SiikaA SzubertAJet al.12\u2010week raltegravir\u2010intensified quadruple therapy versus triple first\u2010line ART reduces viral load more rapidly but does not reduce mortality in severely immunosuppressed African HIV\u2010infected adults and older children: the REALITY trial International AIDS Conference 2016; Durban South Africa."},{"key":"e_1_2_7_10_1","first-page":"220","article-title":"Nuke\u2010sparing regimens for the long\u2010term care of HIV infection","volume":"17","author":"Pasquau J","year":"2015","journal-title":"AIDS Rev"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(16)30015-7"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13181-013-0325-8"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-016-0588-4"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv429"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000662"},{"key":"e_1_2_7_16_1","unstructured":"DHHS.Guidelines for the use of antiretroviral agents in HIV\u20101\u2010infected adults and adolescents.2016.https:\/\/aidsinfonihgov\/guidelines\/html\/1\/adult-and-adolescent-treatment-guidelines\/0. 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