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
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.