Immunotherapy for Infectious Diseases

INTRODUCTION
Immune Reconstitution
with Antiretroviral Chemotherapy
From: Immunotherapy for Infectious Diseases
Edited by: J. M. Jacobson © Humana Press Inc., Totowa, NJ
163
9
Elizabeth Connick
Infection with HIV-1 results in the progressive loss of CD4� T-lymphocytes and a
variety of immune functions, leading ultimately to premature death in most untreated
individuals. The introduction of potent combination antiretroviral chemotherapy for
HIV-1 infection in the mid-1990s resulted in unprecedented decreases in HIV-1 replication
and increases in CD4� T-cell counts in many treated individuals. Simultaneous
to the introduction of potent combination antiviral drug therapy, substantial declines in
morbidity and mortality from HIV-1-associated illnesses have been observed. The
study of immune reconstitution in the context of viral suppression has already provided
some important insights into the immune pathogenesis of HIV-1. Many questions
remain, however, concerning the extent and clinical significance of the immune reconstitution
that occurs in the setting of antiretroviral drug therapy.
IMPACT OF ANTIRETROVIRAL CHEMOTHERAPY
ON HIV-1-RELATED MORBIDITY AND MORTALITY
Before the introduction of potent antiretroviral therapy for HIV-1 infection, the standard
of care for treatment consisted of monotherapy and dual therapy with HIV-1
nucleoside analog reverse transcriptase inhibitors. These therapies were shown to produce
modest increases in CD4� T-cell counts and some improvements in survival
(1–4). With the introduction of protease inhibitors in the mid-1990s and their use in
combination with other antiviral drugs, much more profound and sustained viral suppression
and larger increases in CD4� T-cell counts were observed than ever before.
The first widely used potent combination antiretroviral therapies for HIV-1 infection
consisted of an HIV-1 protease inhibitor and two nucleoside analog reverse transcriptase
inhibitors (5–7). After 6 months of therapy with the HIV-1 protease inhibitor indinavir
and two reverse transcriptase inhibitors, the plasma HIV-1 RNA copy number
was diminished by a median of over 2 log10 in subjects treated with potent antiretroviral
therapy compared with less than 1 log10 in subjects receiving only two nucleoside
analog reverse transcriptase inhibitors (6,7). Increases in CD4� T-lymphocyte