{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T15:17:24Z","timestamp":1767453444993,"version":"build-2065373602"},"reference-count":71,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Poliomyelitis Research Foundation (PRF)","award":["21\/66"],"award-info":[{"award-number":["21\/66"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with efficacy against some NNRTI-resistant mutants. Although DOR resistance mutations are established for HIV-1 subtype B, it is less clear for non-B subtypes. This study investigated prevalent NNRTI resistance mutations on DOR susceptibility in HIV-1 subtype C. Prevalent drug resistance mutations were identified from a South African genotypic drug resistance testing database. Mutations, single or in combination, were introduced into replication-defective pseudoviruses and assessed for DOR susceptibility in vitro. The single V106M and Y188L mutations caused high-level resistance while others did not significantly impact DOR susceptibility. We observed an agreement between our in vitro and the Stanford HIVdb predicted susceptibilities. However, the F227L mutation was predicted to cause high-level DOR resistance but was susceptible in vitro. Combinations of mutations containing K103N, V106M or Y188L caused high-level resistance, in agreement with the predictions. These mutations are frequently observed in patients failing efavirenz- or nevirapine-based first-line regimens. However, they are also observed in those failing a protease inhibitor-based second-line regimen, as we have observed in our database. Genotypic drug resistance testing is therefore vital prior to the initiation of DOR-based treatment for those previously exposed to efavirenz or nevirapine.<\/jats:p>","DOI":"10.3390\/v16091493","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T03:36:38Z","timestamp":1727062598000},"page":"1493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["K103N, V106M and Y188L Significantly Reduce HIV-1 Subtype C Phenotypic Susceptibility to Doravirine"],"prefix":"10.3390","volume":"16","author":[{"given":"Nikita","family":"Reddy","sequence":"first","affiliation":[{"name":"HIV Pathogenesis Research Unit, University of the Witwatersrand, Johannesburg 2193, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Papathanasopoulos","sequence":"additional","affiliation":[{"name":"HIV Pathogenesis Research Unit, University of the Witwatersrand, Johannesburg 2193, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3226-7685","authenticated-orcid":false,"given":"Kim","family":"Steegen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Haematology, School of Pathology, Faculty of Health Science, University of the Witwatersrand, Johannesburg 2193, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7541-8132","authenticated-orcid":false,"given":"Adriaan Erasmus","family":"Basson","sequence":"additional","affiliation":[{"name":"HIV Pathogenesis Research Unit, University of the Witwatersrand, Johannesburg 2193, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/S0140-6736(81)92740-9","article-title":"Kaposi\u2019s Sarcoma in Homosexual Men-a Report of Eight Cases","volume":"2","author":"Hymes","year":"1981","journal-title":"Lancet"},{"key":"ref_2","unstructured":"UNAIDS (2023). Global HIV & AIDS Statistics\u2014Fact Sheet, 2023 Estimates, Joint United Nations Programme on HIV\/AIDS."},{"key":"ref_3","unstructured":"WHO (2023). Epidemiological Fact Sheet\u2014HIV Statistics, Globally and by WHO Region, 2023, World Health Organ."},{"key":"ref_4","unstructured":"UNAIDS (2023). Global HIV & AIDS Statistics\u2014Country Fact Sheet\u2014South Africa, 2023 Estimates, Joint United Nations Programme on HIV\/AIDS."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Elangovan, R., Jenks, M., Yun, J., Dickson-Tetteh, L., Kirtley, S., Hemelaar, J., WHO-UNAIDS Network for HIV Isolation and Characterisation, Abimiku, A.G., Agwale, S., and Archibald, C. (2021). Global and Regional Estimates for Subtype-Specific Therapeutic and Prophylactic HIV-1 Vaccines: A Modeling Study. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.690647"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Giovanetti, M., Ciccozzi, M., Parolin, C., and Borsetti, A. (2020). Molecular Epidemiology of HIV-1 in African Countries: A Comprehensive Overview. Pathogens, 9.","DOI":"10.3390\/pathogens9121072"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1093\/infdis\/jiad327","article-title":"Geographic and Population Distributions of Human Immunodeficiency Virus (HIV)\u20131 and HIV-2 Circulating Subtypes: A Systematic Literature Review and Meta-Analysis (2010\u20132021)","volume":"228","author":"Williams","year":"2023","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1177\/0956462414525769","article-title":"A Systematic Review of Cohort Studies of the Quality of Life in HIV\/AIDS Patients after Antiretroviral Therapy","volume":"25","author":"Jin","year":"2014","journal-title":"Int. J. STD AIDS"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"HIV-CAUSAL Collaboration, Ray, M., Logan, R., Sterne, J.A.C., Hern\u00e1ndez-D\u00edaz, S., Robins, J.M., Sabin, C., Bansi, L., van Sighem, A., and de Wolf, F. (2010). The Effect of Combined Antiretroviral Therapy on the Overall Mortality of HIV-Infected Individuals. AIDS, 24, 123\u2013137.","DOI":"10.1097\/QAD.0b013e3283324283"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1097\/QAD.0b013e32832b7dca","article-title":"Sexual Transmission of HIV According to Viral Load and Antiretroviral Therapy: Systematic Review and Meta-Analysis","volume":"23","author":"Attia","year":"2009","journal-title":"AIDS"},{"key":"ref_11","first-page":"299","article-title":"Adherence to Antiretroviral Therapy and Associated Factors among People Living with HIV\/AIDS in Hara Town and Its Surroundings, North-Eastern Ethiopia: A Cross-Sectional Study","volume":"29","author":"Legesse","year":"2019","journal-title":"Ethiop. J. Health Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1093\/infdis\/jiaa683","article-title":"Clinical Impact of Pretreatment Human Immunodeficiency Virus Drug Resistance in People Initiating Nonnucleoside Reverse Transcriptase Inhibitor\u2013Containing Antiretroviral Therapy: A Systematic Review and Meta-Analysis","volume":"224","author":"Bertagnolio","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_13","first-page":"559","article-title":"2022 Update of the Drug Resistance Mutations in HIV-1","volume":"30","author":"Wensing","year":"2022","journal-title":"Top. Antivir. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S1473-3099(17)30702-8","article-title":"HIV-1 Drug Resistance before Initiation or Re-Initiation of First-Line Antiretroviral Therapy in Low-Income and Middle-Income Countries: A Systematic Review and Meta-Regression Analysis","volume":"18","author":"Gupta","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Moyo, S., Hunt, G., Zuma, K., Zungu, M., Marinda, E., Mabaso, M., Kana, V., Kalimashe, M., Ledwaba, J., and Naidoo, I. (2020). HIV Drug Resistance Profile in South Africa: Findings and Implications from the 2017 National HIV Household Survey. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0241071"},{"key":"ref_16","first-page":"100","article-title":"Adverse Reactions to Dolutegravir Reported to the National HIV & TB Health Care Worker Hotline in South Africa","volume":"1","author":"Tatz","year":"2021","journal-title":"Depression"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e25484","DOI":"10.1002\/jia2.25484","article-title":"Weight Gain among Treatment-Na\u00efve Persons with HIV Starting Integrase Inhibitors Compared to Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors in a Large Observational Cohort in the United States and Canada","volume":"23","author":"Bourgi","year":"2020","journal-title":"J. Int. AIDS Soc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1093\/cid\/ciz999","article-title":"Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials","volume":"71","author":"Sax","year":"2020","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1128\/AAC.02650-15","article-title":"Doravirine Suppresses Common Nonnucleoside Reverse Transcriptase Inhibitor-Associated Mutants at Clinically Relevant Concentrations","volume":"60","author":"Feng","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1177\/1060028020935763","article-title":"Doravirine Use in Treatment-Experienced HIV-Positive Patients","volume":"55","author":"Fulco","year":"2021","journal-title":"Ann. Pharmacother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1097\/QAI.0000000000002153","article-title":"Efficacy and Safety of Doravirine\/Lamivudine\/Tenofovir Disoproxil Fumarate (DOR\/3TC\/TDF) in Treatment-Naive Adults With HIV-1 and Transmitted Nonnucleoside Reverse Transcriptase Inhibitor Resistance Mutations","volume":"82","author":"Wong","year":"2019","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1128\/AAC.04201-14","article-title":"In vitro Resistance Selection with Doravirine (MK-1439), a Novel Nonnucleoside Reverse Transcriptase Inhibitor with Distinct Mutation Development Pathways","volume":"59","author":"Feng","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1128\/AAC.02403-13","article-title":"In vitro Characterization of MK-1439, a Novel HIV-1 Nonnucleoside Reverse Transcriptase Inhibitor","volume":"58","author":"Lai","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/cid\/ciy540","article-title":"Doravirine\/Lamivudine\/Tenofovir Disoproxil Fumarate Is Non-Inferior to Efavirenz\/Emtricitabine\/Tenofovir Disoproxil Fumarate in Treatment-Naive Adults With Human Immunodeficiency Virus\u20131 Infection: Week 48 Results of the DRIVE-AHEAD Trial","volume":"68","author":"Orkin","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1093\/jac\/dkab126","article-title":"Cell Culture Selections Reveal Favourable Drug Resistance Profiles for Doravirine and Islatravir","volume":"76","author":"Brenner","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1097\/QAI.0000000000001031","article-title":"Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants","volume":"72","author":"Smith","year":"2016","journal-title":"JAIDS J. Acquir. Immune Defic. Syndr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"397","DOI":"10.3851\/IMP2920","article-title":"Safety, Tolerability and Pharmacokinetics of Doravirine, a Novel HIV Non-Nucleoside Reverse Transcriptase Inhibitor, after Single and Multiple Doses in Healthy Subjects","volume":"20","author":"Anderson","year":"2015","journal-title":"Antivir. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1007\/s40262-019-00806-9","article-title":"Clinical Pharmacodynamics, Pharmacokinetics, and Drug Interaction Profile of Doravirine","volume":"58","author":"Boyle","year":"2019","journal-title":"Clin. Pharmacokinet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/cid\/ciaa822","article-title":"Doravirine\/Lamivudine\/Tenofovir Disoproxil Fumarate (TDF) Versus Efavirenz\/Emtricitabine\/TDF in Treatment-Naive Adults With Human Immunodeficiency Virus Type 1 Infection: Week 96 Results of the Randomized, Double-Blind, Phase 3 DRIVE-AHEAD Noninferiority Trial","volume":"73","author":"Orkin","year":"2021","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1016\/S2352-3018(19)30336-4","article-title":"Doravirine versus Ritonavir-Boosted Darunavir in Antiretroviral-Naive Adults with HIV-1 (DRIVE-FORWARD): 96-Week Results of a Randomised, Double-Blind, Non-Inferiority, Phase 3 Trial","volume":"7","author":"Molina","year":"2020","journal-title":"Lancet HIV"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e75","DOI":"10.1016\/S2352-3018(23)00258-8","article-title":"Safety and Efficacy of Doravirine as First-Line Therapy in Adults with HIV-1: Week 192 Results from the Open-Label Extensions of the DRIVE-FORWARD and DRIVE-AHEAD Phase 3 Trials","volume":"11","author":"Orkin","year":"2024","journal-title":"Lancet HIV"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1097\/QAI.0000000000002642","article-title":"Brief Report: Switching to DOR\/3TC\/TDF Maintains HIV-1 Virologic Suppression Through Week 144 in the DRIVE-SHIFT Trial","volume":"87","author":"Kumar","year":"2021","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_33","unstructured":"(2019). EACS Guidelines Version 10.0 November 2019, European AIDS Clinical Society."},{"key":"ref_34","unstructured":"(2019). FDA Approves First Two-Drug Complete Regimen for HIV-Infected Patients Who Have Never Received Antiretroviral Treatment."},{"key":"ref_35","unstructured":"(2024). SAHPRA\u2019s Registered Health Products Database, South African Health Products Regulatory Authority. Available online: https:\/\/medapps.sahpra.org.za:6006\/."},{"key":"ref_36","unstructured":"NDH (2023). 2023 ART Clinical Guidelines for the Management of HIV in Adults, Pregnancy and Breastfeeding, Adolescents, Children, Infants and Neonates."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9094","DOI":"10.1128\/JVI.02356-08","article-title":"Gag Determinants of Fitness and Drug Susceptibility in Protease Inhibitor-Resistant Human Immunodeficiency Virus Type 1","volume":"83","author":"Parry","year":"2009","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1097\/QAD.0b013e3283398216","article-title":"Full Length HIV-1 Gag Determines Protease Inhibitor Susceptibility within in vitro Assays","volume":"24","author":"Gupta","year":"2010","journal-title":"AIDS"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1126\/science.272.5259.263","article-title":"In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector","volume":"272","author":"Naldini","year":"1996","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2144\/btn-2022-0085","article-title":"A Simple and Economical Site-Directed Mutagenesis Method for Large Plasmids by Direct Transformation of Two Overlapping PCR Fragments","volume":"73","author":"Yang","year":"2022","journal-title":"BioTechniques"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1086\/503914","article-title":"Web Resources for HIV Type 1 Genotypic-Resistance Test Interpretation","volume":"42","author":"Liu","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/nar\/gkg100","article-title":"Human Immunodeficiency Virus Reverse Transcriptase and Protease Sequence Database","volume":"31","author":"Rhee","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S51","DOI":"10.1086\/505356","article-title":"Rationale and Uses of a Public HIV Drug-Resistance Database","volume":"194","author":"Shafer","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1093\/jac\/dkt316","article-title":"Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Cross-Resistance: Implications for Preclinical Evaluation of Novel NNRTIs and Clinical Genotypic Resistance Testing","volume":"69","author":"Melikian","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/QAI.0b013e31823df4da","article-title":"Genotypic and Phenotypic Characterization of HIV-1 Isolates Obtained From Patients on Rilpivirine Therapy Experiencing Virologic Failure in the Phase 3 ECHO and THRIVE Studies: 48-Week Analysis","volume":"59","author":"Rimsky","year":"2012","journal-title":"JAIDS J. Acquir. Immune Defic. Syndr."},{"key":"ref_46","unstructured":"Tambuyzer, L., Vingerhoets, J., Azijn, H., Daems, B., Nijs, S., de B\u00e9thune, M.-P., and Picchio, G. (2024, March 21). Characterization of Genotypic and Phenotypic Changes in HIV-1-Infected Patients with Virologic Failure on an Etravirine-Containing Regimen in the DUET-1 and DUET-2 Clinical Studies. Available online: https:\/\/www.liebertpub.com\/doi\/10.1089\/aid.2009.0302."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Basson, A.E., Charalambous, S., Hoffmann, C.J., and Morris, L. (2020). HIV-1 Re-Suppression on a First-Line Regimen despite the Presence of Phenotypic Drug Resistance. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0234937"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1128\/AAC.04215-14","article-title":"Impact of Drug Resistance-Associated Amino Acid Changes in HIV-1 Subtype C on Susceptibility to Newer Nonnucleoside Reverse Transcriptase Inhibitors","volume":"59","author":"Basson","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1093\/jac\/dkw358","article-title":"HIV-1 Antiretroviral Drug Resistance Patterns in Patients Failing NNRTI-Based Treatment: Results from a National Survey in South Africa","volume":"72","author":"Steegen","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_50","unstructured":"NDH (2015). National Consolidated Guidelines for the Prevention of Mother-to-Child Transmission of HIV and the Management of HIV in Children, Adolescents and Adults."},{"key":"ref_51","unstructured":"NDH (2019). 2019 ART Clinical Guidelines for the Management of HIV in Adults, Pregnancy and Breastfeeding, Adolescents, Children, Infants and Neonates."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1086\/392517","article-title":"Persistence of HIV Drug Resistance Mutations: More Clues from Clinical Observations","volume":"38","author":"Stein","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5510","DOI":"10.1128\/JVI.02579-07","article-title":"Persistence of Transmitted Drug Resistance among Subjects with Primary Human Immunodeficiency Virus Infection","volume":"82","author":"Little","year":"2008","journal-title":"J. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1097\/00126334-200412150-00006","article-title":"Long-Term Persistence of Primary Genotypic Resistance after HIV-1 Seroconversion","volume":"37","author":"Pao","year":"2004","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Machnowska, P., Meixenberger, K., Schmidt, D., Jessen, H., Hillenbrand, H., Gunsenheimer-Bartmeyer, B., Hamouda, O., K\u00fccherer, C., and Bannert, N. (2019). Prevalence and Persistence of Transmitted Drug Resistance Mutations in the German HIV-1 Seroconverter Study Cohort. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0209605"},{"key":"ref_56","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_57","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/QAI.0b013e31818ffdff","article-title":"Envelope Coreceptor Tropism, Drug Resistance, and Viral Evolution among Subtype C HIV-1-Infected Individuals Receiving Nonsuppressive Antiretroviral Therapy","volume":"50","author":"Kassaye","year":"2009","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1097\/00002030-200404090-00008","article-title":"Genetic Variation at NNRTI Resistance-Associated Positions in Patients Infected with HIV-1 Subtype C","volume":"18","author":"Grossman","year":"2004","journal-title":"AIDS"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"F1","DOI":"10.1097\/00002030-200301030-00001","article-title":"A V106M Mutation in HIV-1 Clade C Viruses Exposed to Efavirenz Confers Cross-Resistance to Non-Nucleoside Reverse Transcriptase Inhibitors","volume":"17","author":"Brenner","year":"2003","journal-title":"AIDS"},{"key":"ref_60","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_61","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1093\/jac\/dkq140","article-title":"Constrained Patterns of Covariation and Clustering of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations","volume":"65","author":"Reuman","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Asante-Appiah, E., Lai, J., Wan, H., Yang, D., Martin, E.A., Sklar, P., Hazuda, D., Petropoulos, C.J., Walworth, C., and Grobler, J.A. (2021). Impact of HIV-1 Resistance-Associated Mutations on Susceptibility to Doravirine: Analysis of Real-World Clinical Isolates. Antimicrob. Agents Chemother., 65.","DOI":"10.1128\/AAC.01216-21"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.ijantimicag.2019.02.007","article-title":"Prevalence of Predicted Resistance to Doravirine in HIV-1-Positive Patients after Exposure to Non-Nucleoside Reverse Transcriptase Inhibitors","volume":"53","author":"Sterrantino","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12981-023-00503-5","article-title":"Potential Role of Doravirine for the Treatment of HIV-1-Infected Persons with Transmitted Drug Resistance","volume":"20","author":"Rhee","year":"2023","journal-title":"AIDS Res. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Obasa, A.E., Engelbrecht, S., and Jacobs, G.B. (2019). Near Full-Length HIV-1 Subtype B Sequences from the Early South African Epidemic, Detecting a BD Unique Recombinant Form (URF) from a Sample in 1985. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-42417-1"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1089\/aid.2005.21.575","article-title":"Full-Length HIV Type 1 Genome Analysis Showing Evidence for HIV Type 1 Transmission from a Nonprogressor to Two Recipients Who Progressed to AIDS","volume":"21","author":"Mikhail","year":"2005","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1089\/aid.2019.0012","article-title":"Low Frequency of Protease Inhibitor Resistance Mutations and Insertions in HIV-1 Subtype C Protease Inhibitor-Na\u00efve Sequences","volume":"35","author":"Ledwaba","year":"2019","journal-title":"AIDS Res. Hum. 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Retroviruses"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1089\/08892220152644232","article-title":"Characterization of Full-Length HIV Type 1 Subtype C Sequences from South Africa","volume":"17","author":"Williamson","year":"2001","journal-title":"AIDS Res. Hum. 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