title: Molecular phylogenetics of transmitted drug resistance in newly diagnosed HIV Type 1 individuals in Denmark: a nation-wide study.
abstract: Highly active antiretroviral treatment is compromised by viral resistance mutations. Transmitted drug resistance (TDR) is therefore monitored closely, but follow-up studies of these patients are limited. Virus from 1405 individuals diagnosed with HIV-1 in Denmark between 2001 and 2009 was analyzed for TDR, and molecular-epidemiological links and progression of the infection were described based on data from standardized questionnaires, the prospective Danish HIV Cohort Study, and by phylogenetic analysis. Eighty-five individuals were found to be infected with virus harboring mutations resulting in a prevalence of 6.1%, with no changes over time. The main resistance mutations were nucleoside reverse transcriptase inhibitor (NRTI) mutation 215 revertants, as well as nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation 103N/S and protease inhibitor (PI) mutations 90M and 85V. Phylogenetic analysis confirmed 12 transmission chains involving 37 TDR individuals. Of these 21 were also documented epidemiologically. The virus included in the transmission chain carried similar resistance mutations to the TDR index case, whereas controls chains from index cases without TDR were generally without resistance mutations. We observed no difference in progression of the infection between individuals infected with TDR and individuals infected with wild-type HIV-1. The prevalence of TDR is low in Denmark and transmission of dual-drug-resistant HIV-1 is infrequent. The TDR isolates were shown to originate from local patients failing therapy.
authors.affiliation: Statens Serum Institut, Copenhagen, Denmark. aud@ssi.dk
authors.forename: Anne Margrethe
authors.initials: AM
authors.lastname: Audelin
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.forename: Lars
authors.initials: L
authors.lastname: Mathiesen
authors.forename: Alex
authors.initials: A
authors.lastname: Laursen
authors.forename: Court
authors.initials: C
authors.lastname: Pedersen
authors.forename: Henrik
authors.initials: H
authors.lastname: Nielsen
authors.forename: Janne
authors.initials: J
authors.lastname: Jensen
authors.forename: Lars
authors.initials: L
authors.lastname: Nielsen
authors.forename: Claus
authors.initials: C
authors.lastname: Nielsen
authors.forename: Louise Bruun
authors.initials: LB
authors.lastname: Jørgensen
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D023241:Antiretroviral Therapy, Highly Active; D003718:Denmark; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D010802:Phylogeny; D011379:Prognosis