title: Emergence of human immunodeficiency virus type 1 variants containing the Q151M complex in children receiving long-term antiretroviral chemotherapy.
abstract: We examined 28 children with HIV-1 infection who were not responding to existing antiviral regimens and were enrolled into clinical trials conducted at the National Cancer Institute to receive salvage therapy. In 3 of the 28 patients (10.7%), the Q151M complex amino acid substitutions were identified. The three patients had received nucleoside reverse transcriptase inhibitor (NRTI) monotherapy and/or combination regimens with multiple NRTIs for 4.3-8.6 years prior to the study. Recombinant infectious clones generated by incorporating the RT-encoding region of HIV-1 isolated from patients' plasma samples were highly resistant to zidovudine, didanosine and stavudine, while they were moderately resistant to lamivudine and tenofovir disoproxil fumarate (TDF). TDF-containing regimens reduced HIV-1 viremia in two of the three children carrying the Q151M complex. These data suggest that the Q151M could be prevalent in pediatric patients with long-term NRTI monotherapy and/or dual NRTI regimens and that HAART regimens containing TDF may be meritorious in such patients.
authors.affiliation: Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Harada
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Tamiya
authors.forename: Steven L
authors.initials: SL
authors.lastname: Zeichner
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mitsuya
mesh_terms: D019943:Amino Acid Substitution; D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002461:Cell Line, Transformed; D002648:Child; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016879:Salvage Therapy; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
chemical_list: D044966:Anti-Retroviral Agents; D011480:Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease