{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T10:01:31Z","timestamp":1764842491217,"version":"build-2065373602"},"reference-count":87,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["This work has been funded by Portuguese National funds, through the Foundation for Science and Technology (FCT) (project UIDB\/50026\/2020 and UIDP\/50026\/2020; by the projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, supported by Norte Por"],"award-info":[{"award-number":["This work has been funded by Portuguese National funds, through the Foundation for Science and Technology (FCT) (project UIDB\/50026\/2020 and UIDP\/50026\/2020; by the projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, supported by Norte Por"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008\u20132017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p &lt; 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p &lt; 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.<\/jats:p>","DOI":"10.3390\/ijms22105304","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T12:17:16Z","timestamp":1621340236000},"page":"5304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6410-7972","authenticated-orcid":false,"given":"Ana","family":"Santos-Pereira","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"given":"Vera","family":"Triunfante","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"given":"Pedro M. M.","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"given":"Joana","family":"Martins","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"given":"Helena","family":"Soares","sequence":"additional","affiliation":[{"name":"Human Immunobiology and Pathogenesis Laboratory, 1150-082 Lisbon, Portugal"},{"name":"CEDOC-Chronic Diseases Research Center, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NOVA University of Lisbon, 1150-082 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4835-9875","authenticated-orcid":false,"given":"Eva","family":"Poveda","sequence":"additional","affiliation":[{"name":"Group of Virology and Pathogenesis, Galicia Sur Health Research Institute (IIS Galicia Sur)-Complexo Hospitalario Universitario de Vigo, SERGAS-UVigo, 36213 Vigo, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4083-3050","authenticated-orcid":false,"given":"Bernardino","family":"Souto","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"},{"name":"Department of Medicine, Federal University of S\u00e3o Carlos, S\u00e3o Paulo 13565-905, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0949-5399","authenticated-orcid":false,"given":"Nuno S.","family":"Os\u00f3rio","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,18]]},"reference":[{"key":"ref_1","unstructured":"Joint United Nations Programme on HIV\/AIDS (2020). UNAIDS Data 2020."},{"key":"ref_2","unstructured":"Souza, P.R.B.D., Szwarcwald, C.L., and Castilho, E.A.D. (2011). Self-rated health by HIV-infected individuals undergoing antiretroviral therapy in Brazil. Cad. Sa\u00fade P\u00fablica\/Minist\u00e9rio Sa\u00fade, Funda\u00e7\u00e3o Oswaldo Cruz. Esc. Nac. Sa\u00fade P\u00fablica."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/hiv.12421","article-title":"Life expectancy of HIV-positive people after starting combination antiretroviral therapy: A meta-analysis","volume":"18","author":"Teeraananchai","year":"2017","journal-title":"HIV Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e349","DOI":"10.1016\/S2352-3018(17)30066-8","article-title":"Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: A collaborative analysis of cohort studies","volume":"4","author":"Trickey","year":"2017","journal-title":"Lancet HIV"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1001\/jama.2020.17025","article-title":"Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-USA Panel","volume":"324","author":"Saag","year":"2020","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1016\/S2352-3018(17)30204-7","article-title":"Prevention of HIV transmission by antiretroviral therapy","volume":"5","author":"Lundgren","year":"2018","journal-title":"Lancet HIV"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1001\/jama.2018.21167","article-title":"HIV viral load and transmissibility of HIV infection undetectable equals untransmittable","volume":"321","author":"Eisinger","year":"2019","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1056\/NEJMoa1600693","article-title":"Antiretroviral Therapy for the Prevention of HIV-1 Transmission","volume":"375","author":"Cohen","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Tanaka, T.S.O., Leite, T.F., Freitas, S.Z., Cesar, G.A., De Rezende, G.R., Lindenberg, A.D.S.C., Guimar\u00e3es, M.L., and Motta-Castro, A.R.C. (2019). HIV-1 molecular epidemiology, transmission clusters and transmitted drug resistance mutations in central Brazil. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.00020"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1093\/jac\/dkm082","article-title":"Prevalence and determinants of transmitted antiretroviral drug resistance in HIV-1 infection","volume":"59","author":"Booth","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Arruda, M.B., Boullosa, L.T., Cardoso, C.C., da Costa, C.M., Brites, C., de Lima, S.T.S., Kaminski, H.T., Aleixo, A.W., Esposito, A.O.P., and Cavalcanti, A.M.S. (2018). Brazilian network for HIV drug resistance surveillance (HIV-BresNet): A survey of treatment-naive individuals. J. Int. AIDS Soc., 21.","DOI":"10.1002\/jia2.25032"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/QCO.0b013e328013caff","article-title":"Epidemiology of antiretroviral drug resistance in drug-na\u00efve persons","volume":"20","author":"Geretti","year":"2007","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_13","first-page":"17","article-title":"Temporal changes in the epidemiology of transmission of drug-resistant HIV-1 across the world","volume":"14","author":"Frentz","year":"2012","journal-title":"AIDS Rev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sui, H., Gui, T., Jia, L., Guo, W., Han, J., Liu, Y., Bao, Z., Li, H., Li, J., and Li, L. (2014). Different Frequencies of Drug Resistance Mutations among HIV-1 Subtypes Circulating in China: A Comprehensive Study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091803"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1089\/aid.2010.0050","article-title":"Impact of HIV type 1 subtype on drug resistance mutations in Nigerian patients failing first-line therapy","volume":"27","author":"Chaplin","year":"2011","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bahls, L.D., Canezin, P.H., Reiche, E.M.V., Fernandez, J.C.C., Dias, J.R.C., Meneguetti, V.A.F., Ueda, L.T., and Bertolini, D.A. (2019). Moderate prevalence of HIV-1 transmitted drug resistance mutations in southern Brazil. AIDS Res. Ther.","DOI":"10.1186\/s12981-019-0219-1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.bjid.2016.11.009","article-title":"Trends and predictors of HIV-1 acquired drug resistance in Minas Gerais, Brazil: 2002\u20132012","volume":"21","author":"Duani","year":"2017","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1590\/S0074-02762007005000109","article-title":"Antiretroviral resistance in individuals presenting therapeutic failure and subtypes of the human immunodeficiency virus type 1 in the Northeast Region of Brazil","volume":"102","author":"Cavalcanti","year":"2007","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/S1413-8670(10)70076-3","article-title":"HIV-1 genotypic resistance profile of patients failing antiretroviral therapy in Paran\u00e1, Brazil","volume":"14","author":"Toledo","year":"2010","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s00705-018-04122-8","article-title":"Prevalence of HIV-1 transmitted drug resistance and viral suppression among recently diagnosed adults in S\u00e3o Paulo, Brazil","volume":"164","author":"Coelho","year":"2019","journal-title":"Arch. Virol."},{"key":"ref_21","unstructured":"Minist\u00e9rio da Sa\u00fade (2018). Clinical Protocol and Therapeutic Guidelines for Handling HIV Infection in Adults."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Benzaken, A.S., Pereira, G.F.M., Costa, L., Tanuri, A., Santos, A.F., and Soares, M.A. (2019). Antiretroviral treatment, government policy and economy of HIV\/AIDS in Brazil: Is it time for HIV cure in the country?. AIDS Res. Ther., 16.","DOI":"10.1186\/s12981-019-0234-2"},{"key":"ref_23","unstructured":"European AIDS Clinical Society (2019). European AIDS clinical society guidelines. Version 10.0. November 2019. IEEE Trans. Sonics Ultrason., 6\u201311."},{"key":"ref_24","unstructured":"(2021, May 18). Panel on Antiretroviral Guidelines for Adults and Adolescents Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, Available online: https:\/\/clinicalinfo.hiv.gov\/sites\/default\/files\/guidelines\/documents\/AdultandAdolescentGL.pdf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/cid\/ciy463","article-title":"Human Immunodeficiency Virus Drug Resistance: 2018 Recommendations of the International Antiviral Society-USA Panel","volume":"68","author":"Calvez","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bennett, D.E., Camacho, R.J., Otelea, D., Kuritzkes, D.R., Fleury, H., Kiuchi, M., Heneine, W., Kantor, R., Jordan, M.R., and Schapiro, J.M. (2009). Drug Resistance Mutations for Surveillance of Transmitted HIV-1 Drug-Resistance: 2009 Update. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004724"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.bjid.2016.03.010","article-title":"Extensive variation in drug-resistance mutational profile of Brazilian patients failing antiretroviral therapy in five large Brazilian cities","volume":"20","author":"Brites","year":"2016","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1093\/cid\/cis1000","article-title":"Impact of HIV-1 Subtype on CD4 Count at HIV Seroconversion, Rate of Decline, and Viral Load Set Point in European Seroconverter Cohorts","volume":"56","author":"Touloumi","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_29","first-page":"111","article-title":"2019 update of the drug resistance mutations in HIV-1","volume":"27","author":"Wensing","year":"2019","journal-title":"Top. Antivir. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1177\/135965350601100209","article-title":"The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations","volume":"11","author":"White","year":"2006","journal-title":"Antivir. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"583","DOI":"10.2217\/hiv.09.40","article-title":"The K65R mutation in HIV-1 reverse transcriptase: Genetic barriers, resistance profile and clinical implications","volume":"3","author":"Brenner","year":"2009","journal-title":"HIV Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1093\/jac\/dkx091","article-title":"An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs","volume":"72","author":"Smit","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1093\/jac\/dkw039","article-title":"Prevalence and dynamics of the K65R drug resistance mutation in HIV-1-infected infants exposed to maternal therapy with lamivudine, zidovudine and either nevirapine or nelfinavir in breast milk","volume":"71","author":"Inzaule","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1128\/AAC.01668-12","article-title":"HIV-1 subtype is an independent predictor of reverse transcriptase mutation k65r in HIV-1 patients treated with combination antiretroviral therapy including tenofovir","volume":"57","author":"Theys","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Coutsinos, D., Invernizzi, C.F., Moisi, D., Oliveira, M., Martinez-Cajas, J.L., Brenner, B.G., and Wainberg, M.A. (2011). A Template-Dependent Dislocation Mechanism Potentiates K65R Reverse Transcriptase Mutation Development in Subtype C Variants of HIV-1. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020208"},{"key":"ref_36","unstructured":"Minist\u00e9rio da Sa\u00fade (2018). Boletim Epidemiol\u00f3gico de HIV e Aids."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/sysbio\/syq010","article-title":"New Algorithms and Methods to Estimate Maximum-Likelihood Phylogenies: Assessing the Performance of PhyML 3.0","volume":"59","author":"Guindon","year":"2010","journal-title":"Syst. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1089\/aid.2009.0012","article-title":"Primary antiretroviral drug resistance among HIV Type 1-infected individuals in Brazil","volume":"25","author":"Sprinz","year":"2009","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Lopes, C.A.F., Soares, M.A., Falci, D.R., and Sprinz, E. (2015). The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil. Biomed. Res. Int., 2015.","DOI":"10.1155\/2015\/738528"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Diaz, R.S., Inoc\u00eancio, L.A., Sucupira, M.C.A., Pereira, A.A., Hunter, J., Ferreira, J.E., Ara\u00fajo, L.V., Souza, D.F.C., and Sabino, E.C. (2015). The Virological and Immunological Characteristics of the HIV-1-Infected Population in Brazil: From Initial Diagnosis to Impact of Antiretroviral Use. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0139677"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.1128\/AAC.47.11.3478-3484.2003","article-title":"Tenofovir Resistance and Resensitization","volume":"47","author":"Wolf","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3579","DOI":"10.1128\/JVI.74.8.3579-3585.2000","article-title":"The M184V Mutation in the Reverse Transcriptase of Human Immunodeficiency Virus Type 1 Impairs Rescue of Chain-Terminated DNA Synthesis","volume":"74","author":"Arion","year":"2000","journal-title":"J. Virol."},{"key":"ref_43","first-page":"31","article-title":"Rationale for maintenance of the M184v resistance mutation in human immunodeficiency virus type 1 reverse transcriptase in treatment experienced patients","volume":"27","author":"Turner","year":"2004","journal-title":"New Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Pingarilho, M., Pimentel, V., Diogo, I., Fernandes, S., Miranda, M., Pineda-Pena, A., Libin, P., Theys, K., Martins, M.R.O., and Vandamme, A.M. (2020). Increasing Prevalence of HIV-1 Transmitted Drug Resistance in Portugal: Implications for First Line Treatment Recommendations. Viruses, 12.","DOI":"10.1101\/2020.03.17.20033092"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Franzetti, M., Violin, M., Antinori, A., De Luca, A., Ceccherini-Silberstein, F., Gianotti, N., Torti, C., Bonora, S., Zazzi, M., and Balotta, C. (2014). Trends and correlates of HIV-1 resistance among subjects failing an antiretroviral treatment over the 2003\u20132012 decade in Italy. BMC Infect. Dis., 14.","DOI":"10.1186\/1471-2334-14-398"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.cmi.2017.06.014","article-title":"Longitudinal trends of HIV drug resistance in a large Canadian cohort, 1996\u20132016","volume":"24","author":"Rocheleau","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_47","unstructured":"Minist\u00e9rio da Sa\u00fade (2013). Protocolo Cl\u00ednico E Diretrizes Terap\u00eatuicas Para O Manejo Da Infec\u00e7\u00e3o Pelo HIV."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1128\/AAC.44.9.2475-2484.2000","article-title":"Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy","volume":"44","author":"Bacheler","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1002\/cmdc.201100362","article-title":"Docking Analysis and Resistance Evaluation of Clinically Relevant Mutations Associated with the HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors Nevirapine, Efavirenz and Etravirine","volume":"6","author":"Alcaro","year":"2011","journal-title":"Chem. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4999","DOI":"10.1128\/JVI.75.11.4999-5008.2001","article-title":"Genotypic Correlates of Phenotypic Resistance to Efavirenz in Virus Isolates from Patients Failing Nonnucleoside Reverse Transcriptase Inhibitor Therapy","volume":"75","author":"Bacheler","year":"2001","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4080","DOI":"10.3390\/v6104080","article-title":"The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance","volume":"6","author":"Garforth","year":"2014","journal-title":"Viruses"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ayitewala, A., Kyeyune, F., Ainembabazi, P., Nabulime, E., Kato, C.D., and Nankya, I. (2020). Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. AIDS Res. Ther., 17.","DOI":"10.1186\/s12981-020-0258-7"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.jphs.2018.11.016","article-title":"Incidence and types of HIV-1 drug resistance mutation among patients failing first-line antiretroviral therapy","volume":"139","author":"Luo","year":"2019","journal-title":"J. Pharmacol. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"291","DOI":"10.3851\/IMP3299","article-title":"Evolution of HIV-1 drug resistance after virological failure of first-line antiretroviral therapy in Lusaka, Zambia","volume":"24","author":"Mulenga","year":"2019","journal-title":"Antivir. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Van Zyl, G.U., Liu, T.F., Claassen, M., Engelbrecht, S., de Oliveira, T., Preiser, W., Wood, N.T., Travers, S., and Shafer, R.W. (2013). Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First-and Second-Line Antiretroviral Treatment Regimens. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067188"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ijid.2017.10.020","article-title":"HIV drug resistance following a decade of the free antiretroviral therapy programme in India: A review","volume":"66","author":"Karade","year":"2018","journal-title":"Int. J. Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e84","DOI":"10.1016\/S2352-3018(19)30404-7","article-title":"Antiretroviral resistance and management after pre-exposure to prophylaxis","volume":"7","author":"Tittle","year":"2020","journal-title":"Lancet HIV"},{"key":"ref_58","first-page":"2197","article-title":"Evolution of the K65R, K103N and M184V\/I reverse transcriptase mutations in HIV-1-infected patients experiencing virological failure between 2005 and 2010","volume":"68","author":"Charpentier","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1093\/jac\/dks380","article-title":"Decreasing population selection rates of resistance mutation K65R over time in HIV-1 patients receiving combination therapy including tenofovir","volume":"68","author":"Theys","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Dolling, D., Sabin, C., Delpech, V., Smit, E., Pozniak, A., Asboe, D., Brown, A.L., Churchill, D., Williams, I., and Geretti, A.M. (2012). Time trends in drug resistant HIV-1 infections in the United Kingdom up to 2009: Multicentre observational study. BMJ, 345.","DOI":"10.1136\/bmj.e5253"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s00430-015-0448-4","article-title":"Prevalence of K65R in patients treated with tenofovir disoproxil fumarate: Recommendations based on the Frankfurt HIV Cohort Study Resistance Database (FHCS-RD)","volume":"205","author":"Reinheimer","year":"2016","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_62","unstructured":"Minist\u00e9rio da Sa\u00fade (2018). Protocolo Cl\u00ednico E Diretrizes Terap\u00eauticas Para Profilaxia Pr\u00e9-Exposi\u00e7\u00e3o (Prep) De Risco \u00c0 Infec\u00e7\u00e3o Pelo HIV."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s40265-019-01108-x","article-title":"Drug Resistance During HIV Pre-Exposure Prophylaxis","volume":"79","author":"Gibas","year":"2019","journal-title":"Drugs"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/COH.0000000000000209","article-title":"Should we fear resistance from tenofovir\/emtricitabine preexposure prophylaxis?","volume":"11","author":"Parikh","year":"2016","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4087","DOI":"10.1128\/AAC.00816-06","article-title":"In vitro human immunodeficiency virus type 1 resistance selections with combinations of tenofovir and emtricitabine or abacavir and lamivudine","volume":"50","author":"Margot","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.1128\/AAC.47.11.3377-3383.2003","article-title":"Molecular impact of the M184V mutation in human immunodeficiency virus type 1 reverse transcriptase","volume":"47","author":"Diallo","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Wagner, B.G., Garcia-Lerma, J.G., and Blower, S. (2012). Factors limiting the transmission of HIV mutations conferring drug resistance: Fitness costs and genetic bottlenecks. Sci. Rep., 2.","DOI":"10.1038\/srep00320"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1128\/JCM.43.3.1395-1400.2005","article-title":"Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation","volume":"43","author":"Weber","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Chan, P.A., Huang, A., and Kantor, R. (2012). Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: Implications for pre-exposure prophylaxis. J. Int. AIDS Soc., 15.","DOI":"10.7448\/IAS.15.2.17701"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1093\/infdis\/jix015","article-title":"Commonly transmitted HIV-1 drug resistance mutations in reverse-transcriptase and protease in antiretroviral treatment-naive patients and response to regimens containing tenofovir disoproxil fumarate or tenofovir alafenamide","volume":"215","author":"Margot","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Rhee, S.Y., Jordan, M.R., Raizes, E., Chua, A., Parkin, N., Kantor, R., Van Zy, G.U., Mukui, I., Hosseinipour, M.C., and Frenkel, L.M. (2015). HIV-1 drug resistance mutations: Potential applications for point-of-care Genotypic resistance testing. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145772"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S1473-3099(15)00536-8","article-title":"Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: A multicentre retrospective cohort study","volume":"16","author":"Gregson","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Kl\u00f8verpris, H.N., Leslie, A., and Goulder, P. (2016). Role of HLA adaptation in HIV evolution. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00665"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1097\/BOR.0b013e328362018f","article-title":"HLA-B27-mediated protection in HIV and hepatitis C virus infection and pathogenesis in spondyloarthritis: Two sides of the same coin?","volume":"25","year":"2013","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"R158","DOI":"10.1186\/ar4341","article-title":"Prevalence of HLA-B27 in the New Zealand population: Effect of age and ethnicity","volume":"15","author":"Roberts","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1002\/art.33503","article-title":"The prevalence of HLA-B27 in the US: Data from the US National Health and Nutrition Examination Survey, 2009","volume":"64","author":"Reveille","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1097\/00002281-199507000-00001","article-title":"HLA-B27 and its subtypes in world populations: Editorial review","volume":"7","author":"Khan","year":"1995","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Ara\u00fajo, P.M.M., Martins, J.S., and Os\u00f3rio, N.S. (2019). SNAPPy: A snakemake pipeline for scalable HIV-1 subtyping by phylogenetic pairing. Virus Evol., 5.","DOI":"10.1093\/ve\/vez050"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1093\/nar\/gkp371","article-title":"jpHMM: Improving the reliability of recombination prediction in HIV-1","volume":"37","author":"Schultz","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Katoh, K., and Standley, D.M. (2013). MAFFT multiple sequence alignment software version 7: Improvements in performance and usability. Mol. Biol. Evol.","DOI":"10.1093\/molbev\/mst010"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1093\/molbev\/msx149","article-title":"SMS: Smart Model Selection in PhyML","volume":"34","author":"Lefort","year":"2017","journal-title":"Mol. Biol. Evol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1093\/molbev\/mss075","article-title":"Bayesian phylogenetics with BEAUti and the BEAST 1.7","volume":"29","author":"Drummond","year":"2012","journal-title":"Mol. Biol. Evol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/cjs.5550360302","article-title":"Bayesian analysis of elapsed times in continuous-time Markov chains","volume":"36","author":"Ferreira","year":"2008","journal-title":"Can. J. Stat."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"7223","DOI":"10.1038\/s41598-019-43420-2","article-title":"Characterization of a large cluster of HIV-1 A1 infections detected in Portugal and connected to several Western European countries","volume":"9","author":"Carvalho","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"W246","DOI":"10.1093\/nar\/gkw359","article-title":"PHYLOViZ Online: Web-based tool for visualization, phylogenetic inference, analysis and sharing of minimum spanning trees","volume":"44","author":"Francisco","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"W449","DOI":"10.1093\/nar\/gkaa379","article-title":"NetMHCpan-4.1 and NetMHCIIpan-4.0: Improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data","volume":"48","author":"Reynisson","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_87","first-page":"D783","article-title":"Allele frequency net database (AFND) 2020 update: Gold-standard data classification, open access genotype data and new query tools","volume":"48","author":"McCabe","year":"2020","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/10\/5304\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:03:14Z","timestamp":1760162594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/10\/5304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,18]]},"references-count":87,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22105304"],"URL":"https:\/\/doi.org\/10.3390\/ijms22105304","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,5,18]]}}}