Wa. Marasco et al., Human anti-HIV-1 tat sFv intrabodies for gene therapy of advanced HIV-1-infection and AIDS, J IMMUNOL M, 231(1-2), 1999, pp. 223-238
The early successes of highly active anti-retroviral therapies (HAART) for
the treatment of HIV-1-infection and AIDS have raised the question as to wh
ether there is a legitimate role for gene therapy in the treatment of this
chronic infectious disease. However, in many patients the profound suppress
ion of viral replication is short lived, particularly if patients have been
treated with sequential monotherapies in the past, have been infected with
a highly drug resistant isolate of HIV-1, or have temporarily discontinued
therapy as a "holiday" or because of drug intolerance. In addition, life-l
ong adherence to maintenance HAART will probably be required even in respon
ding patients with undetectable viremia because of the reservoirs of latent
ly infected cells that can persist for years. Gene therapy through the intr
oduction of anti-retroviral "resistance" genes into CD4(+) T cells is one a
pproach that could give long term protection to these HIV-1 susceptible cel
ls in vivo. We have explored this approach by developing intrabodies to the
critical HIV-1 transactivator protein, Tat that is absolutely required for
HIV-1 replication. This provocative treatment approach, that will be teste
d in a clinical gene therapy trial, sets the groundwork for determining if
anti-Tat intrabody gene therapy together with HAART can provide a treatment
strategy for the immune reconstitution of HIV-1-infected patients with adv
anced disease. (C) 1999 Elsevier Science B.V. All rights reserved.