title: Persistent production of an integrase-deleted HIV-1 variant with no resistance mutation and wild-type proviral DNA in a treated patient.
abstract: An HIV-infected patient presenting an unexpected viral escape under combined antiretroviral treatment is described. The virus isolated from plasma contained a large deletion in the HIV-1 integrase gene but no known resistance mutation. Nested polymerase chain reactions (PCRs) with patient virus integrase-specific primers and probes were developed and used to detect the mutant from plasma, blood, rectal biopsies, and sperm. The variant progressively emerged during a period of therapy-induced virosuppression, and persisted at a low but detectable level for at least 5 years. Surprisingly, proviral DNA from lymphocytes, rectal cells, and sperm cells was, and remained, mainly wild type. Cellular HIV RNA with the deletion was detected only once from the rectum. The origin and mechanisms underlying this so far not described production at a detectable level are largely hypothetical. This observation raised concern about the ability of defective viruses to spread.
authors.affiliation: 1 Laboratoire de Virologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon , Lyon, France .
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Trabaud
authors.forename: Laurent
authors.initials: L
authors.lastname: Cotte
authors.forename: Julien
authors.initials: J
authors.lastname: Saison
authors.forename: Christophe
authors.initials: C
authors.lastname: Ramière
authors.forename: Corinne
authors.initials: C
authors.lastname: Ronfort
authors.forename: Fabienne
authors.initials: F
authors.lastname: Venet
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardy
authors.forename: Guillaume
authors.initials: G
authors.lastname: Monneret
authors.forename: Patrice
authors.initials: P
authors.lastname: André
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D003673:Defective Viruses / Q000235:genetics / Q000472:pathogenicity*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D057131:Immune Evasion / Q000235:genetics; D019426:Integrases / Q000235:genetics*; D019259:Lamivudine / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000821:virology; D061466:Lopinavir / Q000627:therapeutic use; D008969:Molecular Sequence Data; D011533:Proviruses / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D019562:Viral Load / Q000187:drug effects; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D019426:Integrases