Treatment-naive individuals are the major source of transmitted HIV-1 drug resistance in men who have sex with men in the Swiss HIV Cohort Study

Drescher, Sara M; von Wyl, Viktor; Yang, Wan-Lin; Böni, Jürg; Yerly, Sabine; Shah, Cyril; Aubert, Vincent; Klimkait, Thomas; Taffé, Patrick; Furrer, Hansjakob; Battegay, Manuel; Ambrosioni, Juan; Cavassini, Matthias; Bernasconi, Enos; Vernazza, Pietro L; Ledergerber, Bruno; Günthard, Huldrych F; Kouyos, Roger D; Egger, M; Keiser, O; ... (2014). Treatment-naive individuals are the major source of transmitted HIV-1 drug resistance in men who have sex with men in the Swiss HIV Cohort Study. Clinical infectious diseases, 58(2), pp. 285-94. Oxford University Press 10.1093/cid/cit694

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BACKGROUND Human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) and thus represents an important public health concern. Typically, sources of TDR remain unknown, but they can be characterized with molecular epidemiologic approaches. We used the highly representative Swiss HIV Cohort Study (SHCS) and linked drug resistance database (SHCS-DRDB) to analyze sources of TDR. METHODS ART-naive men who have sex with men with infection date estimates between 1996 and 2009 were chosen for surveillance of TDR in HIV-1 subtype B (N = 1674), as the SHCS-DRDB contains pre-ART genotypic resistance tests for >69% of this surveillance population. A phylogeny was inferred using pol sequences from surveillance patients and all subtype B sequences from the SHCS-DRDB (6934 additional patients). Potential sources of TDR were identified based on phylogenetic clustering, shared resistance mutations, genetic distance, and estimated infection dates. RESULTS One hundred forty of 1674 (8.4%) surveillance patients carried virus with TDR; 86 of 140 (61.4%) were assigned to clusters. Potential sources of TDR were found for 50 of 86 (58.1%) of these patients. ART-naive patients constitute 56 of 66 (84.8%) potential sources and were significantly overrepresented among sources (odds ratio, 6.43 [95% confidence interval, 3.22-12.82]; P < .001). Particularly large transmission clusters were observed for the L90M mutation, and the spread of L90M continued even after the near cessation of antiretroviral use selecting for that mutation. Three clusters showed evidence of reversion of K103N or T215Y/F. CONCLUSIONS Many individuals harboring viral TDR belonged to transmission clusters with other Swiss patients, indicating substantial domestic transmission of TDR in Switzerland. Most TDR in clusters could be linked to sources, indicating good surveillance of TDR in the SHCS-DRDB. Most TDR sources were ART naive. This, and the presence of long TDR transmission chains, suggests that resistance mutations are frequently transmitted among untreated individuals, highlighting the importance of early diagnosis and treatment.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine

UniBE Contributor:

von Wyl, Viktor; Furrer, Hansjakob; Egger, Matthias; Keiser, Olivia; Rauch, Andri and Schöni-Affolter, Franziska

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

1058-4838

Publisher:

Oxford University Press

Language:

English

Submitter:

Doris Kopp Heim

Date Deposited:

19 Mar 2014 17:18

Last Modified:

27 Apr 2018 08:33

Publisher DOI:

10.1093/cid/cit694

PubMed ID:

24145874

Additional Information:

Swiss H. I. V. Cohort Study (Members from the Univ Bern: Egger M, Furrer H, Keiser O, Rauch A, Schöni-Affolter F)

Uncontrolled Keywords:

genotypic resistance testing molecular epidemiology transmitted antiretroviral drug resistance

BORIS DOI:

10.7892/boris.41400

URI:

https://boris.unibe.ch/id/eprint/41400

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