title: Infrequent transmission of HIV-1 drug-resistant variants.
abstract: Transmission of drug-resistant variants is influenced by several factors, including the prevalence of drug resistance in the population of HIV-1-infected patients, HIV-1 RNA levels and transmission by recently infected patients. In order to evaluate the impact of these factors on the transmission of drug-resistant variants, we have defined the population of potential transmitters and compared their resistance profiles to those of newly infected patients. Sequencing of pol gene was performed in 220 recently infected patients and in 373 chronically infected patients with HIV-1 RNA >1000 copies/ml. Minimal and maximal drug-resistance profiles of potential transmitters were estimated by weighting resistance profiles of chronically infected patients with estimates of the Swiss HIV-1-infected population, the prevalence of exposure to antiviral drugs and the proportion of infections attributed to primary HIV infections. The drug-resistance prevalence in recently infected patients was 10.5% (one class drug resistance: 9.1%; two classes: 1.4%; three classes: 0%). Phylogenetic analysis revealed significant clustering for 30% of recent infections. The drug-resistance prevalence in chronically infected patients was 72.4% (one class: 29%; two classes: 27.6%; three classes: 15.8%). After adjustment, the risk of transmission relative to wild-type was reduced both for one class drug resistance (minimal and maximal estimates: odds ratio: 0.39, P<0.001; and odds ratio: 0.55, P=0.011, respectively), and for two to three class drug resistance (odds ratios: 0.05 and 0.07, respectively, P<0.001). Neither sexual behaviour nor HIV-1 RNA levels explained the low transmission of drug-resistant variants. These data suggest that drug-resistant variants and in particular multidrug-resistant variants have a substantially reduced transmission capacity.
authors.affiliation: Laboratory of Virology and AIDS Center, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Jost
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
authors.forename: Markus
authors.initials: M
authors.lastname: Flepp
authors.forename: Laurent
authors.initials: L
authors.lastname: Kaiser
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Chave
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Bruno
authors.initials: B
authors.lastname: Chanzy
authors.forename: Philippe
authors.initials: P
authors.lastname: Burgisser
authors.forename: Martin
authors.initials: M
authors.lastname: Rickenbach
authors.forename: Martin
authors.initials: M
authors.lastname: Gebhardt
authors.forename: Marie-Charlotte
authors.initials: MC
authors.lastname: Bernard
authors.forename: Thomas
authors.initials: T
authors.lastname: Perneger
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Luc
authors.initials: L
authors.lastname: Perrin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D018562:Disease Transmission, Infectious; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015751:Genes, pol; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010802:Phylogeny; D015995:Prevalence; D012367:RNA, Viral / Q000032:analysis; D012307:Risk Factors; D013557:Switzerland / Q000453:epidemiology
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral