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Can
Therapeutic Immunization with DermaVir Control HIV Rebound?
The objective of the current study was to reconstitute immune responses
capable of eliminating infected cells and suppressing viral
load during chronic retroviral infection.
To
achieve this, a topical, DNA-based therapeutic
immunization (DermaVir) was designed to express most
of the regulatory and structural viral genes in dendritic cells.
DermaVir
alone and in combination with antiretroviral
drugs was tested in chronically SIV-infected macaques.
Results
DermaVir
provided virological, immunological and clinical benefit for SIV-infected
macaques during chronic infection and AIDS. In combination with
antiretroviral drugs, DermaVir augmented SIV-specific T-cell responses
and enhanced control of viral load rebound during treatment
interruptions.
The
authors conclude, “The results indicate the feasibility of therapeutic
immunization even in immune compromised hosts, and suggest that
DermaVir can complement antiretroviral drugs to sustain suppression
of HIV-1 replication.”
Discussion
As
DermaVir immunization was more effective in combination with antiretroviral
drugs; the investigators do not view DermaVir as a substitute for
antiretroviral drugs, rather as a potential new therapy with a unique
mechanism of action.
Therapeutic
immunizations
are expected to have a resistance profile different from those of
nucleoside reverse transcriptase inhibitors, non-nucleoside reverse
transcriptase inhibitors, protease inhibitors, and other drugs.
As
such, therapeutic immunizations might improve the durability of
the presently used drugs by preventing viral rebound in case of
lack of adherence or when patients temporarily stop drugs due to
toxicity . The authors write, “Here we have demonstrated that the
repeated immunization schedule is feasible and desirable treatment
approach with DermaVir.” The topical administration and absence
of common toxicities with antiretroviral drugs might be also appealing
to patients.
DermaVir
represents an advancement in the field of therapeutic immunization,
as it exerts antiviral activity during chronic and late stage retroviral
infection. Others have demonstrated inhibition of SIV replication
with dendritic cell-based ex vivo therapeutic immunization
early after infection, when the immune system is still preserved
and has the best chances of achieving immune reconstitution even
with the host's own virus.
Unfortunately,
ex vivo techniques are cumbersome, expensive, and limited
to highly specialized laboratories.
In
closing, the authors note, “In contrast, DermaVir utilizes a needle-free,
topical application that can be manufactured for large-scale human
use and repeatedly administered. The results presented here further
support the feasibility of DermaVir immunization for the treatment
of chronic HIV infection.”
Research Institute for Genetic and Human Therapy (RIGHT);
Genetic Immunity, LLC, Washington DC; Southern Research Institute,
Frederick, Maryland, USA; Clinical Epidemiology and Biometry Unit,
IRCCS G. Gaslini, Genova, Italy; National Institutes of Health,
National Cancer Institute, Bethesda, Maryland, USA.
01/10/05
Reference
J
Lisziewicz and others. Control of viral rebound through therapeutic
immunization with DermaVir.
AIDS 19(1):
35-43, January 3, 2005.
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