{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:18:17Z","timestamp":1760145497963,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T00:00:00Z","timestamp":1722384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fonds de Recherche du Qu\u00e9bec-R\u00e9seau SIDA","award":["339583","15291","23131"],"award-info":[{"award-number":["339583","15291","23131"]}]},{"name":"Gilead Sciences","award":["339583","15291","23131"],"award-info":[{"award-number":["339583","15291","23131"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: HIV drug resistance (HIV-DR) may jeopardize the benefit of antiretroviral therapy (ART) in treatment and prevention. This study utilized viral phylogenetics to resolve the influence of transmission networks on sustaining the spread of HIV-DR in Quebec spanning 2002 to 2022. Methods: Time trends in acquired (ADR) and transmitted drug resistance (TDR) were delineated in treatment-experienced (n = 3500) and ART-na\u00efve persons (n = 6011) with subtype B infections. Similarly, non-B-subtype HIV-DR networks were assessed pre- (n = 1577) and post-ART experience (n = 488). Risks of acquisition of resistance-associated mutations (RAMs) were related to clustering using 1, 2\u20135, vs. 6+ members per cluster as categorical variables. Results: Despite steady declines in treatment failure and ADR since 2007, rates of TDR among newly infected, ART-naive persons remained at 14% spanning the 2007\u20132011, 2012\u20132016, and 2017\u20132022 periods. Notably, half of new infections among men having sex with men and heterosexual groups were linked in large, clustered networks having a median of 35 (14\u201373 IQR) and 16 (9\u201326 IQR) members per cluster, respectively. Cluster membership and size were implicated in forward transmission of non-nucleoside reverse transcriptase inhibitor NNRTI RAMs (9%) and thymidine analogue mutations (TAMs) (5%). In contrast, transmission of M184V, K65R, and integrase inhibitors (1\u20132%) remained rare. Levels of TDR reflected viral replicative fitness. The median baseline viremia in ART-na\u00efve groups having no RAMs, NNRTI RAMs, TAMs, and M184VI were 46.088, 38,447, 20,330, and 6811 copies\/mL, respectively (p &lt; 0.0001). Conclusion: Phylogenetics emphasize the need to prioritize ART and pre-exposure prophylaxis strategies to avert the expansion of transmission cascades of HIV-DR.<\/jats:p>","DOI":"10.3390\/v16081230","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T17:16:49Z","timestamp":1722446209000},"page":"1230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phylogenetic Network Analyses Reveal the Influence of Transmission Clustering on the Spread of HIV Drug Resistance in Quebec from 2002 to 2022"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2084-728X","authenticated-orcid":false,"given":"Bluma G.","family":"Brenner","sequence":"first","affiliation":[{"name":"McGill University Centre for Viral Diseases, Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada"},{"name":"Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada"},{"name":"Department of Medicine (Surgery, Infectious Disease), McGill University, Montreal, QC H3A 0G4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruxandra-Ilinca","family":"Ibanescu","sequence":"additional","affiliation":[{"name":"McGill University Centre for Viral Diseases, Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen","family":"Oliveira","sequence":"additional","affiliation":[{"name":"McGill University Centre for Viral Diseases, Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillaume","family":"Margaillan","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie et d\u2019Immunologie et Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Montreal, QC H2X 0C1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1273-9393","authenticated-orcid":false,"given":"Bertrand","family":"Lebouch\u00e9","sequence":"additional","affiliation":[{"name":"Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00e9jean","family":"Thomas","sequence":"additional","affiliation":[{"name":"Clinique M\u00e9dicale l\u2019Actuel, Montreal, QC H2L 4P9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Guy","family":"Baril","sequence":"additional","affiliation":[{"name":"Clinique M\u00e9dicale du Quartier Latin, Montreal, QC H2L 4E9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9-Pierre","family":"Lorgeoux","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc., Montreal, QC L5N 7K2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Roger","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie et d\u2019Immunologie et Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Montreal, QC H2X 0C1, Canada"},{"name":"Primary HIV Infection (PHI) Cohort, Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9897-7589","authenticated-orcid":false,"given":"Jean-Pierre","family":"Routy","sequence":"additional","affiliation":[{"name":"Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the Montreal Primary HIV Infection (PHI) Cohort Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,31]]},"reference":[{"key":"ref_1","unstructured":"UNAIDS Global AIDS Update 2023 (2023). The Path That Ends AIDS, Joint United Nations Programme on HIV\/AIDS. Available online: https:\/\/thepath.unaids.org\/wp-content\/themes\/unaids2023\/assets\/files\/2023_report.pdf."},{"key":"ref_2","unstructured":"World Health Organization (2024, July 24). Tackling Drug Resistance: Trends, Guidelines and Global Action. Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/255881\/WHO-HIV-2017.21-eng.pdf."},{"key":"ref_3","unstructured":"World Health Organization (2024, July 24). HIV Drug Resistance Report 2021. Available online: https:\/\/www.aidsdatahub.org\/sites\/default\/files\/resource\/who-hiv-drug-resistance-report-2021.pdf."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Sanaubarova, A., Pujol-Hodge, E., Dzissyuk, N., Lemey, P., Vermund, S.H., Leigh Brown, A.J., and Ali, S. (2023). High-Level Drug-Resistant Mutations among HIV-1 Subtype A6 and CRF02_AG in Kazakhstan. Viruses, 15.","DOI":"10.3390\/v15071407"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1093\/infdis\/jiab413","article-title":"Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients","volume":"225","author":"Palich","year":"2022","journal-title":"J. Infect. Dis."},{"key":"ref_6","first-page":"1355","article-title":"WHO Documents Rising Resistance to First-Line HIV Drug","volume":"331","author":"Harris","year":"2024","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1007\/s40121-022-00676-y","article-title":"HIV DNA Sequencing to Detect Archived Antiretroviral Drug Resistance","volume":"11","author":"Geretti","year":"2022","journal-title":"Infect. Dis. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"ofad526","DOI":"10.1093\/ofid\/ofad526","article-title":"Virologic Response to Dolutegravir Plus Lamivudine in People With Suppressed Human Immunodeficiency Virus Type 1 and Historical M184V\/I: A Systematic Literature Review and Meta-analysis","volume":"10","author":"Kabra","year":"2023","journal-title":"Open Forum Infect. Dis."},{"key":"ref_9","unstructured":"Landman, R., Assoumou, L., Lambert-Niclot, S., Amat, K., Katlama, C., Allavena, C., Lacombe, K., Bouchaud, O., de Castro, N., and Moins, C. (2023, January 18\u201321). ANRS 177 DUETTO randomized, open-label and multicentric trial evaluating the non-inferiority of maintenance antiretroviral dual therapy taken 4 consecutive days per week versus dual therapy 7\/7 days per week. Proceedings of the 19th European AIDS Conference, Warsaw, Poland. poster eP.A.106."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Brenner, B.G., Ibanescu, R.I., Osman, N., Cuadra-Foy, E., Oliveira, M., Chaillon, A., Stephens, D., Hardy, I., Routy, J.P., and Thomas, R. (2021). The Role of Phylogenetics in Unravelling Patterns of HIV Transmission towards Epidemic Control: The Quebec Experience (2002\u20132020). Viruses, 13.","DOI":"10.3390\/v13081643"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1002\/jmv.22047","article-title":"Subtype diversity associated with the development of HIV-1 resistance to integrase inhibitors","volume":"83","author":"Brenner","year":"2011","journal-title":"J. Med. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Campbell, E.M., Boyles, A., Shankar, A., Kim, J., Knyazev, S., Cintron, R., and Switzer, W.M. (2021). MicrobeTrace: Retooling molecular epidemiology for rapid public health response. PLoS Comput. Biol., 17.","DOI":"10.1371\/journal.pcbi.1009300"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e684","DOI":"10.1016\/S2352-3018(23)00173-X","article-title":"Checklist for studies of HIV drug resistance prevalence and incidence (CEDRIC-HIV): Rationale and recommended use","volume":"10","author":"Mbuagbaw","year":"2023","journal-title":"Lancet HIV"},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1093\/jac\/dkz417","article-title":"Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance","volume":"75","author":"Tzou","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1089\/aid.2022.0065","article-title":"Dynamics of Rilpivirine Resistance-Associated Mutation: E138 in Reverse Transcriptase among Antiretroviral-Naive HIV-1-Infected Individuals in Turkey","volume":"39","author":"Sayan","year":"2023","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4681","DOI":"10.1128\/AAC.01029-13","article-title":"Basis for early and preferential selection of the E138K mutation in HIV-1 reverse transcriptase","volume":"57","author":"McCallum","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1097\/QAD.0000000000003648","article-title":"Adherence to oral antiretroviral therapy in Canada, 2010\u20132020","volume":"37","author":"Angel","year":"2023","journal-title":"AIDS"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1093\/cid\/ciae016","article-title":"Virological failure after switch to long-acting cabotegravir and rilpivirine injectable therapy: An in-depth analysis","volume":"79","author":"Gisolf","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1093\/jac\/dkad258","article-title":"Archived rilpivirine-associated resistance mutations among ART-naive and virologically suppressed people living with HIV-1 subtype C in Botswana: Implications for cabotegravir\/rilpivirine use","volume":"78","author":"Maruapula","year":"2023","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1093\/jac\/dkad184","article-title":"Doravirine responses to HIV-1 viruses bearing mutations to NRTIs and NNRTIs under in vitro selective drug pressure","volume":"78","author":"Brenner","year":"2023","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.1093\/jac\/dkab161","article-title":"Prevalence of genotypic baseline risk factors for cabotegravir + rilpivirine failure among ARV-naive patients","volume":"76","author":"Charpentier","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1093\/cid\/ciad370","article-title":"Expanded Multivariable Models to Assist Patient Selection for Long-Acting Cabotegravir + Rilpivirine Treatment: Clinical Utility of a Combination of Patient, Drug Concentration, and Viral Factors Associated With Virologic Failure","volume":"77","author":"Orkin","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","unstructured":"Planinic, A., Begovac, J., Rokic, F., Simicic, P., Oroz, M., Jakovac, K., Vugrek, O., and Zidovec-Lepej, S. (2023). Characterization of Human Immunodeficiency Virus-1 Transmission Clusters and Transmitted Drug-Resistant Mutations in Croatia from 2019 to 2022. Viruses, 15.","DOI":"10.3390\/v15122408"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1097\/QAD.0000000000002883","article-title":"Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: A multivariable analysis","volume":"35","author":"Cutrell","year":"2021","journal-title":"AIDS"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1097\/QAD.0000000000003505","article-title":"Impact of rilpivirine cross-resistance on long-acting cabotegravir-rilpivirine in low and middle-income countries","volume":"37","author":"Steegen","year":"2023","journal-title":"AIDS"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/8\/1230\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:27:16Z","timestamp":1760110036000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/8\/1230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,31]]},"references-count":28,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["v16081230"],"URL":"https:\/\/doi.org\/10.3390\/v16081230","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2024,7,31]]}}}