{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:56:45Z","timestamp":1792022205503,"version":"4.4.0"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["AC17\/00019, PI18\/00154, COV20\/00349, ICI20\/00058"],"award-info":[{"award-number":["AC17\/00019, PI18\/00154, COV20\/00349, ICI20\/00058"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The initiation of antiretroviral treatment based on a 2-drug regimen (2DR) with dolutegravir plus lamivudine has demonstrated non-inferior efficacy than dolutegravir-based three-drug regimens (3DR). We aimed to assess whether the treatment initiation with this 2DR has a different impact on the CD4\/CD8 ratio recovery than INSTI-based 3DR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We emulated a target trial using observational data from the Spanish HIV Research Network cohort (CoRIS). The outcomes of interest were the normalization of the CD4\/CD8 ratio at 48 weeks using three different cutoffs: 0.5, 1.0, and 1.5. We matched each participant who started 2DR with up to four participants who received 3DR. Subsequently, we fitted generalized estimating equation (GEE) models and used the Kaplan\u2013Meier method for survival curves.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 485, 805, and 924 participants for cutoffs of 0.5, 1.0, and 1.5, respectively. At 48 weeks, 45% of participants achieved a CD4\/CD8 ratio &amp;gt;0.5, 15% achieved a ratio &amp;gt;1.0, and 6% achieved a ratio &amp;gt;1.5. GEE models yielded a similar risk of reaching a CD4\/CD8 ratio &amp;gt;0.5 (OR 1.00, 95% CI 0.67 - 1.50), CD4\/CD8 &amp;gt;1.0 (OR 1.03, 95% CI 0.68 - 1.58), and CD4\/CD8 &amp;gt;1.5 (OR 0.86, 95% CI 0.48 - 1.54) between both treatment strategies. There were no differences between 2DR and 3DR in the incidence ratio of CD4\/CD8 ratio normalization at 0.5, 1.0 and 1.5 cut-offs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this large cohort study in people with HIV, ART initiation with dolutegravir plus lamivudine vs. dolutegravir or bictegravir-based triple antiretroviral therapy showed no difference in the rates of CD4\/CD8 normalization at 48 weeks.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.873408","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T15:46:55Z","timestamp":1648741615000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Similar CD4\/CD8 Ratio Recovery After Initiation of Dolutegravir Plus Lamivudine Versus Dolutegravir or Bictegravir-Based Three-Drug Regimens in Naive Adults With HIV"],"prefix":"10.3389","volume":"13","author":[{"given":"Javier","family":"Mart\u00ednez-Sanz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Ron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"S\u00e1nchez-Conde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Muriel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Fernando","family":"L\u00f3pez Cort\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Ram\u00f3n","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Antonio","family":"Pineda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Mena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Calzado Isbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Serrano-Villar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32462-0","article-title":"Dolutegravir Plus Lamivudine Versus Dolutegravir Plus Tenofovir Disoproxil Fumarate and Emtricitabine in Antiretroviral-Naive Adults With HIV-1 Infection (GEMINI-1 and GEMINI-2): Week 48 Results From Two Multicentre, Double-Blind, Randomised, non-Inferior","volume":"393","author":"Cahn","year":"2019","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e1004078","DOI":"10.1371\/journal.ppat.1004078","article-title":"HIV-Infected Individuals With Low CD4\/CD8 Ratio Despite Effective Antiretroviral Therapy Exhibit Altered T Cell Subsets, Heightened CD8+ T Cell Activation, and Increased Risk of Non-AIDS Morbidity and Mortality","volume":"10","author":"Serrano-Villar","year":"2014","journal-title":"PloS Pathog"},{"key":"B3","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/S2352-3018(15)00006-5","article-title":"CD4\/CD8 Ratio Normalisation and non-AIDS-Related Events in Individuals With HIV Who Achieve Viral Load Suppression With Antiretroviral Therapy: An Observational Cohort Study","volume":"2","author":"Mussini","year":"2015","journal-title":"Lancet HIV"},{"key":"B4","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1097\/QAD.0000000000001005","article-title":"CD4+\/CD8+ Ratio, Age, and Risk of Serious Noncommunicable Diseases in HIV-Infected Adults on Antiretroviral Therapy","volume":"30","author":"Castilho","year":"2016","journal-title":"AIDS"},{"key":"B5","unstructured":"European AIDS Clinical Society (EACS) Guidelines2021"},{"key":"B6","unstructured":"Department of Health and Human ServicesGuidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(20)30202-2","article-title":"Effects of First-Line Antiretroviral Therapy on the CD4\/CD8 Ratio and CD8 Cell Counts in CoRIS: A Prospective Multicentre Cohort Study","volume":"7","author":"Serrano-Villar","year":"2020","journal-title":"Lancet 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