Origin of Minority Drug-Resistant HIV-1 Variants in Primary HIV-1 Infection
| Autor: | Metzner, K. J., Scherrer, A. U., Preiswerk, B., Joos, B., von Wyl, V., Leemann, C., Rieder, P., Braun, D., Grube, C., Kuster, H., Boni, J., Yerly, S., Klimkait, T., Aubert, V., Furrer, H., Battegay, M., Vernazza, P. L., Cavassini, M., Calmy, A., Bernasconi, E., Weber, R., Gunthard, H. F., Barth, J., Bucher, H. C., Burton-Jeangros, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Fux, C. A., Gorgievski, M., Gunthard, H., Haerry, D., Hasse, B., Hirsch, H. H., Hosli, I., Kahlert, C., Kaiser, L., Keiser, O., Kovari, H., Kouyos, R., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Muller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schoni-Affolter, F., Schupbach, J., Speck, R., Taffe, P., Tarr, P., Telenti, A., Trkola, A. |
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| Přispěvatelé: | University of Zurich, Metzner, Karin J, Swiss HIV Cohort Study, Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kovari, H., Kouyos, R., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A. |
| Rok vydání: | 2013 |
| Předmět: |
Male
HIV Infections Drug resistance Polymerase Chain Reaction law.invention 10234 Clinic for Infectious Diseases Cohort Studies 0302 clinical medicine law Adolescent Adult Aged Alleles Cluster Analysis Drug Resistance Viral Female Genetic Variation HIV Infections/transmission HIV Infections/virology HIV-1/drug effects HIV-1/genetics Humans Middle Aged Phylogeny Sequence Analysis DNA Switzerland Young Adult Immunology and Allergy 030212 general & internal medicine Young adult 610 Medicine & health Polymerase chain reaction ddc:616 0303 health sciences biology Transmission (medicine) Resistance mutation 3. Good health Integrase Infectious Diseases 2723 Immunology and Allergy Peripheral blood mononuclear cell 03 medical and health sciences Allele 030304 developmental biology HIV-1/drug effects/genetics/isolation & purification 2725 Infectious Diseases HIV Infections/transmission/virology Virology Immunology HIV-1 biology.protein |
| Zdroj: | Journal of Infectious Diseases The Journal of Infectious Diseases, Vol. 208, No 7 (2013) pp. 1102-12 The Journal of Infectious Diseases Journal of Infectious Diseases, vol. 208, no. 7, pp. 1102-1112 Journal of Infectious Diseases; Vol 208 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jit310 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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