title: pol gene sequence variation in Swedish HIV-2 patients failing antiretroviral therapy.
abstract: There is limited knowledge about how to treat and interpret results from genotypic resistance assays in HIV-2 infection. Here, genetic variation in HIV-2 pol gene was studied in 20 of 23 known HIV-2 cases in Sweden. Five patients with signs of virological treatment failure were longitudinally studied. Clinical, virological and immunological data were collected and the protease (PR) and first half of the reverse transcriptase (RT) was amplified and directly sequenced from plasma samples. Moderate to extensive genetic evolution was observed in four of the five patients who failed treatment. Some mutations occurred at positions known to confer resistance in HIV-1, but many occurred at other positions in PR and RT. All patients had been treated with zidovudine alone or in combination with other antiretroviral drugs, but none displayed a mutation at position 215, which is the primary zidovudine resistance site in HIV-1. Instead, a E219D mutation evolved in virus from two patients and a Q151M mutation evolved in two other patients. A M184V mutation indicative of lamivudine resistance was detected in three patients. The virus of one patient who had been treated with ritonavir, nelfinavir, and lopinavir successively acquired nine unusual mutations in the protease gene, most of which are not considered primary or secondary resistance mutations in HIV-1. Our data indicate that the evolutionary pathways that lead to antiretroviral resistance in HIV-2 and HIV-1 exhibit both similarities and differences. Genotypic HIV-2 resistance assays cannot be interpreted using algorithms developed for HIV-1, instead new algorithms specific for HIV-2 have to be developed.
authors.affiliation: Division of Clinical Virology, Department of Laboratory Medicine, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge/Stockholm, Sweden.
authors.forename: Eleonor
authors.initials: E
authors.lastname: Brandin
authors.forename: Lena
authors.initials: L
authors.lastname: Lindborg
authors.forename: Katarina
authors.initials: K
authors.lastname: Gyllensten
authors.forename: Christina
authors.initials: C
authors.lastname: Broström
authors.forename: Lars
authors.initials: L
authors.lastname: Hagberg
authors.forename: Magnus
authors.initials: M
authors.lastname: Gisslen
authors.forename: Björn
authors.initials: B
authors.lastname: Tuvesson
authors.forename: Anders
authors.initials: A
authors.lastname: Blaxhult
authors.forename: Jan
authors.initials: J
authors.lastname: Albert
mesh_terms: D000293:Adolescent; D000328:Adult; D000354:Africa, Western / Q000208:ethnology; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D003062:Codon / Q000235:genetics; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D015751:Genes, pol; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D015498:HIV-2 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D019888:Nelfinavir / Q000494:pharmacology / Q000627:therapeutic use; D011446:Prospective Studies; D011744:Pyrimidinones / Q000494:pharmacology / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013548:Sweden; D017211:Treatment Failure; D014766:Viremia / Q000188:drug therapy / Q000821:virology*; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D003062:Codon; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D019888:Nelfinavir; D019438:Ritonavir