{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T12:42:29Z","timestamp":1761396149961,"version":"3.40.5"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Aim<\/jats:title><jats:p>Combined antiretroviral treatment (cART) traditionally consists of three antiretroviral medications, while two-drug regimens (2DR), historically used infrequently, recently been suggested to be non-inferior to three-drug regimens, is emerging as a potential treatment option and is currently a recommended option for treatment initiation in many guidelines.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Purpose<\/jats:title><jats:p>Characterize the indications and clinical efficacy of 2DR use at a real-life setting in a nation-wide survey.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Methods<\/jats:title><jats:p>A cross-sectional survey of Israeli patients treated by 2DR until July 2019, included demographic, immunologic, virologic, genotypic and biochemical\/metabolic parameters at diagnosis, ART initiation, 2DR initiation and following 24, 48, 96 and 144 weeks of 2DR treatment.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Results<\/jats:title><jats:p>176 patients were included in the study. In contrast to historical data implicating ART resistance and adverse effects as the major reasons leading to 2DR switching, treatment simplification was the main reason leading to 2DR treatment in 2019. 2DR that included INSTI and PI were more commonly used in cases of drug resistance, while a combination of INSTI and NNRTI was used in all other 2DR indications. A switch to 2DR induced a mean CD4 T cell increase from 599 cells\/\u03bcl at treatment initiation to 680 cells\/\u03bcl at 96 weeks of treatment p&lt;0.001 and viral suppression improvement from 73.9% at initiation to 87.0% at 48 weeks of treatment (p = 0.004). PI and INSTI 2DR was inferior in suppressing viral levels compared to other 2DRs but used for subset of more complex patients.<\/jats:p><\/jats:sec><jats:sec id=\"sec005\"><jats:title>Conclusions<\/jats:title><jats:p>2DR in a large-scale real-life nation-wide survey proved to be safe and effective. Most 2DRs, other than PI and INSTI, were similarly effective in suppressing HIV viremia and in elevating CD4 T cell counts.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0259271","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T17:31:35Z","timestamp":1635528695000},"page":"e0259271","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Long term dual antiretroviral therapy: A real life retrospective countrywide Israeli study"],"prefix":"10.1371","volume":"16","author":[{"given":"Daniel","family":"David","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eynat","family":"Kedem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Turner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itzchak","family":"Levy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel G.","family":"Elbirt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Shahar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valery","family":"Istumin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3207-4226","authenticated-orcid":true,"given":"Orna","family":"Mor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Chowers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9046-8130","authenticated-orcid":true,"given":"Hila","family":"Elinav","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"issue":"4","key":"pone.0259271.ref001","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1056\/NEJM198707233170401","article-title":"in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial","volume":"317","author":"MA Fischl","year":"1987","journal-title":"N Engl J Med"},{"issue":"11","key":"pone.0259271.ref002","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1056\/NEJM199709113371102","article-title":"Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy","volume":"337","author":"RM Gulick","year":"1997","journal-title":"N Engl J Med"},{"issue":"11","key":"pone.0259271.ref003","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1056\/NEJM199709113371101","article-title":"A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team","volume":"337","author":"SM Hammer","year":"1997","journal-title":"N Engl J Med"},{"key":"pone.0259271.ref004","first-page":"42","article-title":"Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents","volume":"47","author":"SK Stanley","year":"1998","journal-title":"MMWR"},{"issue":"8","key":"pone.0259271.ref005","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1097\/QAD.0000000000000243","article-title":"Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy","volume":"28","author":"MT May","year":"2014","journal-title":"AIDS"},{"issue":"9635","key":"pone.0259271.ref006","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0140-6736(08)61113-7","article-title":"Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies","volume":"372","author":"C Antiretroviral Therapy Cohort","year":"2008","journal-title":"Lancet"},{"issue":"12","key":"pone.0259271.ref007","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1093\/cid\/ciu701","article-title":"Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGEhIV cohort study","volume":"59","author":"J Schouten","year":"2014","journal-title":"Clin Infect Dis"},{"issue":"2","key":"pone.0259271.ref008","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/QAD.0b013e3283348944","article-title":"The MONET trial: darunavir\/ritonavir with or without nucleoside analogues, for patients with HIV RNA below 50 copies\/ml","volume":"24","author":"JR Arribas","year":"2010","journal-title":"AIDS"},{"issue":"7","key":"pone.0259271.ref009","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S1473-3099(14)70736-4","article-title":"Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial","volume":"14","author":"P Cahn","year":"2014","journal-title":"Lancet Infect Dis"},{"issue":"8","key":"pone.0259271.ref010","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1097\/QAD.0000000000001058","article-title":"Once-daily maraviroc versus tenofovir\/emtricitabine each combined with darunavir\/ritonavir for initial HIV-1 treatment","volume":"30","author":"HJ Stellbrink","year":"2016","journal-title":"AIDS"},{"issue":"1","key":"pone.0259271.ref011","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1093\/cid\/ciw207","article-title":"Maraviroc, as a Switch Option, in HIV-1-infected Individuals With Stable, Well-controlled HIV Replication and R5-tropic Virus on Their First Nucleoside\/Nucleotide Reverse Transcriptase Inhibitor Plus Ritonavir-boosted Protease Inhibitor Regimen: Week 48 Results of the Randomized, Multicenter MARCH Study","volume":"63","author":"SL Pett","year":"2016","journal-title":"Clin Infect Dis"},{"issue":"7","key":"pone.0259271.ref012","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/S1473-3099(15)00097-3","article-title":"Dual treatment with atazanavir-ritonavir plus lamivudine versus triple treatment with atazanavir-ritonavir plus two nucleos(t)ides in virologically stable patients with HIV-1 (SALT): 48 week results from a randomised, open-label, non-inferiority trial","volume":"15","author":"JA Perez-Molina","year":"2015","journal-title":"Lancet Infect Dis"},{"issue":"3","key":"pone.0259271.ref013","doi-asserted-by":"crossref","first-page":"257","DOI":"10.3851\/IMP3095","article-title":"Salvage therapy or simplification of salvage regimens with dolutegravir plus ritonavir-boosted darunavir dual therapy in highly cART-experienced subjects: an Italian cohort.","volume":"22","author":"AF Capetti","year":"2017","journal-title":"Antivir Ther"},{"issue":"1","key":"pone.0259271.ref014","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/s12879-017-2311-2","article-title":"Lamivudine\/dolutegravir dual therapy in HIV-infected, virologically suppressed patients","volume":"17","author":"F Maggiolo","year":"2017","journal-title":"BMC Infect Dis"},{"issue":"8","key":"pone.0259271.ref015","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1093\/jac\/dkw147","article-title":"Virological control and metabolic improvement in HIV-infected, virologically suppressed patients switching to lamivudine\/dolutegravir dual therapy","volume":"71","author":"A Borghetti","year":"2016","journal-title":"J Antimicrob Chemother"},{"issue":"10123","key":"pone.0259271.ref016","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S0140-6736(17)33095-7","article-title":"Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies","volume":"391","author":"JM Llibre","year":"2018","journal-title":"Lancet"},{"issue":"9","key":"pone.0259271.ref017","doi-asserted-by":"crossref","first-page":"e576","DOI":"10.1016\/S2352-3018(19)30149-3","article-title":"Efficacy and safety of dolutegravir-rilpivirine for maintenance of virological suppression in adults with HIV-1: 100-week data from the randomised, open-label, phase 3 SWORD-1 and SWORD-2 studies","volume":"6","author":"M Aboud","year":"2019","journal-title":"Lancet HIV"},{"key":"pone.0259271.ref018","unstructured":"HIV drug resistance database [Internet]. [cited 16.9.2021]. Available from: https:\/\/hivdb.stanford.edu\/."},{"issue":"3","key":"pone.0259271.ref019","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1097\/QAI.0000000000002275","article-title":"Durable Efficacy of Dolutegravir Plus Lamivudine in Antiretroviral Treatment-Naive Adults With HIV-1 Infection: 96-Week Results From the GEMINI-1 and GEMINI-2 Randomized Clinical Trials","volume":"83","author":"P Cahn","year":"2020","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"25","key":"pone.0259271.ref020","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1056\/NEJM199912163412501","article-title":"Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team","volume":"341","author":"S Staszewski","year":"1999","journal-title":"N Engl J Med"},{"journal-title":"European AIDS clinical Society guidelines","year":"2020","author":"MJ Arribas J","key":"pone.0259271.ref021"},{"key":"pone.0259271.ref022","unstructured":"Updated recommendations on HIV prevention, infant diagnosis, antiretroviral initiation and monitoring 2021 [Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240022232."},{"key":"pone.0259271.ref023","unstructured":"Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV 2021 [Available from: https:\/\/clinicalinfo.hiv.gov\/en\/guidelines\/adult-and-adolescent-arv\/whats-new-guidelines."},{"issue":"10167","key":"pone.0259271.ref024","doi-asserted-by":"crossref","first-page":"143","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-inferiority, phase 3 trials","volume":"393","author":"P Cahn","year":"2019","journal-title":"Lancet"},{"issue":"13","key":"pone.0259271.ref025","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1097\/QAD.0000000000002320","article-title":"Uptake and effectiveness of two-drug compared with three-drug antiretroviral regimens among HIV-positive individuals in Europe","volume":"33","author":"B Neesgaard","year":"2019","journal-title":"AIDS"},{"issue":"4","key":"pone.0259271.ref026","first-page":"860","article-title":"Dual therapy based on raltegravir and boosted protease inhibitors\u2014the experience of Polish centers","volume":"14","author":"E Jablonowska","year":"2018","journal-title":"Arch Med Sci"},{"issue":"12","key":"pone.0259271.ref027","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1002\/jmv.24826","article-title":"Efficacy and safety of nucleoside-sparing regimen based on raltegravir and ritonavir-boosted darunavir in HIV-1-infected treatment-experienced patients","volume":"89","author":"E Jablonowska","year":"2017","journal-title":"J Med Virol"},{"key":"pone.0259271.ref028","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.eclinm.2018.11.005","article-title":"Systematic De-escalation of Successful Triple Antiretroviral Therapy to Dual Therapy with Dolutegravir plus Emtricitabine or Lamivudine in Swiss HIV-positive Persons","volume":"6","author":"ND Diaco","year":"2018","journal-title":"EClinicalMedicine"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0259271","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,14]],"date-time":"2023-01-14T04:42:50Z","timestamp":1673671370000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0259271"}},"subtitle":[],"editor":[{"given":"Luis","family":"Men\u00e9ndez-Arias","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,10,29]]},"references-count":28,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0259271","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2021,10,29]]}}}