ANTIVIRAL POTENCY OF DRUG-GENE THERAPY COMBINATIONS AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Citation
U. Junker et al., ANTIVIRAL POTENCY OF DRUG-GENE THERAPY COMBINATIONS AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1, AIDS research and human retroviruses, 13(16), 1997, pp. 1395-1402
Citations number
42
Categorie Soggetti
Immunology,"Infectious Diseases
ISSN journal
08892229
Volume
13
Issue
16
Year of publication
1997
Pages
1395 - 1402
Database
ISI
SICI code
0889-2229(1997)13:16<1395:APODTC>2.0.ZU;2-H
Abstract
Gene therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infection using intracellular immunization strategies is curre ntly being tested in clinical trials, With the continuing development of potent antiretroviral drugs (e.g., reverse transcriptase [RT] and p rotease [PR] inhibitors), it is likely that HIV-1 gene therapy will be applied to humans concurrently receiving such antiretroviral medicati on, In this study, we assessed the in vitro antiviral efficacy of two gene therapy strategies (trans-dominant RevM10, Gag antisense RNA) in combination with clinically relevant RT (AZT, dde) or PR (indinavir) i nhibitors. Retrovirally transduced, human T cell lines expressing anti viral gene constructs were inoculated with high doses of HIV-1(HXB3) i n the presence or absence of inhibitors, The combination of RevM10 or Gag antisense RNA with antiviral drugs inhibited HIV-1 replication 10- fold more effectively than the single antiviral drug regimen alone, Mo re importantly, pre also addressed whether gene therapy strategies are effective against drug-resistant HIV-1 isolates, Both the RevM10 and Gag antisense RNA strategies showed antiviral efficacy against several RT inhibitor-resistant HIV-1 isolates equivalent to their inhibition of HIV-1(HXB3) replication, In summary, our data demonstrate the great er than additive antiviral efficacy of gene therapy strategies and RT or PR inhibitors, and that gene therapy approaches are effective again st drug-resistant HIV-1 viral isolates.