title: Identification of a transmission chain of HIV type 1 containing drug resistance-associated mutations.
abstract: We have investigated a potential transmission chain of HIV-1 with drug resistance-associated mutations between three individuals over a period of 5 years by use of cloning and sequencing of viral genes, and phenotypic characterization. Viruses containing reverse transcriptase drug resistance-associated mutations were transmitted sequentially between three homosexual men (A, B, and C), and persisted in one individual for at least 4 years, despite intermittent therapy and reduced viral replicative capacity compared with wild-type strains. Clonal analysis of the envelope gene from semen and blood virus showed that the virus transmitted to patient C was more closely related to virus from the semen than the blood of patient B. Our data suggest that HIV variants with drug resistance-associated mutations can persist following primary infection, despite intervening antiretroviral therapy, and subsequently sexually transmitted. We provide "proof of principle" that such mutations can therefore become "fixed" within the circulating virus pool.
authors.affiliation: Public Health Laboratory Service Antiviral Susceptibility Reference Unit, Division of Immunity and Infection, University of Birmingham, Birmingham B9 5SS, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Taylor
authors.forename: Patricia
authors.initials: P
authors.lastname: Cane
authors.forename: Stéphane
authors.initials: S
authors.lastname: Hué
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Terri
authors.initials: T
authors.lastname: Wrin
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Lie
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hellmann
authors.forename: Christos
authors.initials: C
authors.lastname: Petropoulos
authors.forename: Judith
authors.initials: J
authors.lastname: Workman
authors.forename: Daina
authors.initials: D
authors.lastname: Ratcliffe
authors.forename: Bhudipa
authors.initials: B
authors.lastname: Choudhury
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000635:transmission* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D012661:Semen / Q000821:virology; D017422:Sequence Analysis, DNA; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D054303:HIV Reverse Transcriptase