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Patients
with a High Pre-HAART CD4+ Cell Count Are at Increased Risk of
Immunological Failure
In
HIV patients, the primary treatment goal of HAART is
to suppress the HIV-1 RNA level in plasma
(i.e., the plasma virus load
[pVL]) to below the level of detection.
In
both cohort studies and randomized clinical
trials (RCTs), a lower pVL has been associated
with a reduction in HIV-1 related morbidity
and mortality. The results of recent cohort
studies and RCTs have, however, suggested
that baseline and time-updated CD4+ cell counts
are better predictors of HIV-1 disease progression
than are pVLs.
Discordant
virological and immunological responses have been
observed during HAART. Similarly, virological and immunological
failure has been observed to occur independently
during HAART. This suggests a complex interaction
between the virological response to HAART and the
resulting change in CD4+ cell count.
In
the results of a previous study from the EuroSIDA
cohort, older age and being naive for antiretroviral
therapy (ART) were identified as predictors of
a sustained virological response during HAART.
Furthermore,
younger age, being naive for ART, and having
a lower baseline pVL and CD4+ cell
count were shown to be independent predictors
of virological failure
in the APROCO cohort.
The
identification of predictors of immunological failure
after the initial response to HAART, which may
be different from predictors of virological failure,
may have implications for the treatment of
patients. These data have not previously been reported
from a large international HIV patient cohort.
The primary aim of the current study was
to investigate predictors of immunological failure
after initial CD4+ response. Data were from
EuroSIDA, a prospective, international, observational
HIV cohort.
Results
Of
2347 patients with an increase in CD4+
cell count  100 cells/mL
within 612 months of the
initiation of HAART, 550 (23%) subsequently experienced
immunological failure (CD4+ count less
than or equal to the pre-HAART value).
The
incidence of failure was 11.6 incidences/100 person-years
of follow-up during the first 12 months and
decreased significantly over time (P <
.0001).
Independent
predictors of immunological failure were pre-HAART
CD4+ cell count, time-updated virus load,
and HIV-1 risk behavior.
Conclusions
The
risk of immunological failure in patients
with an immunological response to HAART diminishes
with a longer time receiving treatment and is
associated with pretreatment CD4+ cell count, ongoing
viral replication, and intravenous drug use.
Discussion
This
study confirmed findings by Deeks et al. that patients
with a high pre-HAART CD4+ cell count are
at an increased risk of immunological failure.
One reason for this finding could lie in the
difference in actual numbers of CD4+
cells at the time of failure, between patients
with high and those with low pre-HAART CD4+
cell counts.
The
authors hypothesize that the reason why patients with
higher pre-HAART CD4+ cell counts were
found to be at increased risk of immunological
failure, compared with those who had lower
pre-HAART CD4+ cell counts, is that the
latter group of patients is at an increased
risk of developing opportunistic diseases (ODs);
thus, clinicians have a lower threshold for
the modification of therapy in these patients, which
thereby prevents or delays the development of immunological
failure.
06/18/04
Reference
U B Dragsted
and others. Predictors of Immunological
Failure after Initial Response
to Highly Active Antiretroviral
Therapy in HIV-1-infected Adults:
A EuroSIDA Study. The Journal of Infectious Diseases 190(1): 148-155. July 1, 2004.
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