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.

TitreTreatment-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.
Publication TypeJournal Article
Year of Publication2014
AuthorsDrescher, SM, von Wyl, V, Yang, W-L, Böni, J, Yerly, S, Shah, C, Aubert, V, Klimkait, T, Taffé, P, Furrer, H, Battegay, M, Ambrosioni, J, Cavassini, M, Bernasconi, E, Vernazza, PL, Ledergerber, B, Günthard, HF, Kouyos, RD
Corporate AuthorsStudy, SHIVCohort
JournalClinical Infectious Diseases
Volume58
Issue2
Pagination285-294
Date Published01/2014
DOI10.1093/cid/cit694
ISSN1058-4838 (linking)
ISBN Number1537-6591 (Electronic)
Mots-clésAdult, Anti-HIV Agents, Cluster Analysis, Cohort Studies, Drug Resistance, Viral, HIV Infections, HIV-1, Homosexuality, Male, Humans, Male, Middle Aged, Molecular Epidemiology, Phylogeny, pol Gene Products, Human Immunodeficiency Virus, Sequence Homology, Switzerland, Young Adult
Abstract

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.

Notes

Publication types: Journal Article Publication Status: ppublish

Alternate URL

http://www.ncbi.nlm.nih.gov/pubmed/24145874?dopt=Abstract

First publication date (online)

10/2013

WOS ID (UT)

000329131300023

Alternate JournalClin. Infect. Dis.
Citation Key / SERVAL ID3500
Peer reviewRefereed
PubMed ID24145874

                         

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