Immunotherapy for Infectious Diseases

From: Immunotherapy for Infectious Diseases
Edited by: J. M. Jacobson © Humana Press Inc., Totowa, NJ
221
12
Host Cell-Directed Approaches for Treating HIV
and Restoring Immune Function
J. Michael Kilby and R. Pat Bucy
INTRODUCTION
Despite a number of recent therapeutic advances, there remains an urgent need for
new approaches to treat HIV infection, the causative agent of AIDS. In this chapter,
treatment strategies are reviewed that target host cell interactions or immune responses,
rather than acting as direct antiviral agents. Certain treatments that target host factors—
such as cytokines, chemokines, immunomodulators, or therapeutic vaccination—will
probably prove to be effective adjuvants to conventional antiviral therapy in the future
and may even hold the potential to alter the natural history of HIV infection in some
individuals.
The demonstration of persistent high levels of HIV replication within the untreated
host, even during the often prolonged asymptomatic course of early HIV infection (1),
has led to a logical therapeutic emphasis on the development of more potent antiviral
drugs. Ground-breaking studies evaluating the responses to antiretroviral regimens
revealed the dynamic nature of viral replication along with the potential to suppress the
amount of viral genetic material (HIV RNA or viral load) in the plasma by 1000-fold
or more (2,3). The critical role of the plasma viral load was further emphasized by the
observation that this measurement is also tightly linked to the rate of disease progression
in untreated patients (4). Larger randomized clinical trials later demonstrated that
individuals treated with highly active antiretroviral therapy (HAART) regimens had
decreases in opportunistic infections and death compared with those treated with less
potent therapies (5,6). Improved clinical outcomes have been well documented outside
of the clinical trial setting as well (7), and for the first time in the history of the epidemic,
a decline in AIDS-related mortality has been noted in the United States. The
dramatic reduction in plasma viral load after HAART treatment is associated with
an apparent halt in disease progression and substantial functional improvement in the
immune system, but such treatment does not bring about complete eradication of
the pathogen. Understanding the host factors that keep viral replication in check during
the prolonged steady-state phase will provide key mechanistic insights, which may
be critical for devising novel therapeutic interventions that will potentially synergize
with antiretroviral regimens to eliminate chronic active infection.