Origin of Minority Drug-Resistant HIV-1 Variants in Primary HIV-1 Infection

Metzner, K. J.; Scherrer, A. U.; Preiswerk, B.; Joos, B.; von Wyl, V.; Leemann, C.; Rieder, P.; Braun, D.; Grube, C.; Kuster, H.; Böni, J.; Yerly, S.; Klimkait, T.; Aubert, V.; Furrer, Hansjakob; Battegay, M.; Vernazza, P. L.; Cavassini, M.; Calmy, A.; Bernasconi, E.; ... (2013). Origin of Minority Drug-Resistant HIV-1 Variants in Primary HIV-1 Infection. Journal of infectious diseases, 208(7), pp. 1102-1112. Oxford University Press 10.1093/infdis/jit310

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Background. Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants (MVs) are present in some antiretroviral therapy (ART)–naive patients. They may result from de novo mutagenesis or transmission. To date, the latter has not been proven. Methods. MVs were quantified by allele-specific polymerase chain reaction in 204 acute or recent seroconverters from the Zurich Primary HIV Infection study and 382 ART-naive, chronically infected patients. Phylogenetic analyses identified transmission clusters. Results. Three lines of evidence were observed in support of transmission of MVs. First, potential transmitters were identified for 12 of 16 acute or recent seroconverters harboring M184V MVs. These variants were also detected in plasma and/or peripheral blood mononuclear cells at the estimated time of transmission in 3 of 4 potential transmitters who experienced virological failure accompanied by the selection of the M184V mutation before transmission. Second, prevalence between MVs harboring the frequent mutation M184V and the particularly uncommon integrase mutation N155H differed highly significantly in acute or recent seroconverters (8.2% vs 0.5%; P < .001). Third, the prevalence of less-fit M184V MVs is significantly higher in acutely or recently than in chronically HIV-1–infected patients (8.2% vs 2.5%; P = .004). Conclusions. Drug-resistant HIV-1 MVs can be transmitted. To what extent the origin—transmission vs sporadic appearance—of these variants determines their impact on ART needs to be further explored.

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

UniBE Contributor:

Furrer, Hansjakob

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0022-1899

Publisher:

Oxford University Press

Language:

English

Submitter:

Annelies Luginbühl

Date Deposited:

21 Mar 2014 10:17

Last Modified:

27 Apr 2018 10:57

Publisher DOI:

10.1093/infdis/jit310

Uncontrolled Keywords:

HIV-1, primary HIV-1 infection, drug resistance, transmission, drug-resistant HIV-1 minority variants, prevalence, allele-specific real-time PCR

BORIS DOI:

10.7892/boris.44217

URI:

https://boris.unibe.ch/id/eprint/44217

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