title: Smaller amounts of antiretroviral drugs are needed when combined with an active ribozyme against HIV-1.
abstract: We have tested for combined anti-HIV-1 effects of a hammerhead ribozyme and antiretroviral drugs and the possibility of reducing the drug burden of patients on highly active antiretroviral therapy (HAART). The antiretroviral compounds used represent the three groups in HAART: nucleoside analogue reverse-transcriptase inhibitors, nonnucleoside reverse-transcriptase inhibitors, and protease inhibitors. A human T cell line (HUT78), stably expressing a hammerhead ribozyme targeted to nef (hhRz.nef(9016-9029)), was infected with HIV-1(SF2) in the presence of a single drug. The combined effects on HIV-1 replication were measured by p24 antigen determinations over a 2-week period. In the presence of the ribozyme, smaller amounts of antiretroviral drugs were required to reduce the HIV-1 p24 levels equally as much as when only drugs were present. The results support a strategy of combining ribozyme gene therapy with HAART to improve the long-term outcome of anti-HIV-1 therapy.
authors.affiliation: Clinical Research Center, Karolinska Institutet, Huddinge University Hospital, Huddinge, 141 86, Sweden. catharina.maijgren-steffensson@kfc.ki.se
authors.forename: C
authors.initials: C
authors.lastname: Maijgren-Steffensson
authors.forename: A
authors.initials: A
authors.lastname: Sönnerborg
authors.forename: A
authors.initials: A
authors.lastname: Vahlne
authors.forename: S
authors.initials: S
authors.lastname: Britton
authors.forename: S
authors.initials: S
authors.lastname: Larsson
authors.forename: L
authors.initials: L
authors.lastname: Ahrlund-Richter
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D048588:Benzoxazines; D002460:Cell Line; D003521:Cyclopropanes; D016049:Didanosine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D019469:Indinavir / Q000494:pharmacology; D019259:Lamivudine / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D016337:RNA, Catalytic / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D016655:HIV Core Protein p24; D017320:HIV Protease Inhibitors; D010078:Oxazines; D011480:Protease Inhibitors; D016337:RNA, Catalytic; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D019469:Indinavir; C098320:efavirenz; D016049:Didanosine