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The development of treatment-emergent resistance to an ARV can limit a patient's options for future therapy, prompting the need for ARV regimens that are resilient to the emergence of resistance. The genetic barrier to resistance refers to the number of mutations in an ARV's therapeutic target that are required to confer a clinically meaningful loss of susceptibility to the drug. The emergence of resistance can be affected by pharmacological aspects of the ARV, including its structure, inhibitory quotient, therapeutic index, and pharmacokinetic characteristics. Dolutegravir (DTG) has demonstrated a high barrier to resistance, including when used in a two-drug regimen (2DR) with lamivudine (3TC). In the GEMINI-1 and GEMINI-2 studies, DTG +3TC was noninferior to DTG + emtricitabine\/tenofovir disoproxil fumarate in treatment-naive participants, with similar proportions achieving HIV-1 RNA &lt;50 copies\/mL through 96 weeks. Furthermore, in the TANGO study, virological suppression was maintained at 48 weeks after switching to DTG +3TC from a tenofovir alafenamide (TAF)-based regimen compared with continuing a TAF-based regimen. Most other 2DRs with successful outcomes compared with three-drug regimens have been based on protease inhibitors (PIs); however, this class is associated with adverse metabolic effects and drug\u2013drug interactions. In this review, we discuss the barrier to resistance in the context of a 2DR in which a boosted PI is replaced with DTG +3TC.<\/jats:p>","DOI":"10.1089\/aid.2019.0171","type":"journal-article","created":{"date-parts":[[2019,9,11]],"date-time":"2019-09-11T05:15:32Z","timestamp":1568178932000},"page":"13-18","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":40,"title":["Perspectives on the Barrier to Resistance for Dolutegravir + Lamivudine, a Two-Drug Antiretroviral Therapy for HIV-1 Infection"],"prefix":"10.1177","volume":"36","author":[{"given":"Marta","family":"Boffito","sequence":"first","affiliation":[{"name":"Chelsea and Westminister Hospital, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Waters","sequence":"additional","affiliation":[{"name":"Mortimer Market Centre, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Cahn","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Hu\u00e9sped, Buenos Aires, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Paredes","sequence":"additional","affiliation":[{"name":"Hospital Germans Trias i Pujol, Catalonia, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Koteff","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Research Triangle Park, North Carolina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Van Wyk","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Brentford, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tia","family":"Vincent","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Brentford, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Demarest","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Research Triangle Park, North Carolina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly","family":"Adkison","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Brentford, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina","family":"Quercia","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Brentford, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,12,31]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/sti.79.3.176"},{"key":"e_1_3_3_3_2","first-page":"69","article-title":"Genetic barriers to resistance and impact on clinical response","volume":"7","author":"Luber AD","year":"2005","unstructured":"Luber AD: Genetic barriers to resistance and impact on clinical response. 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