Discordant Immunologic and Virologic Responses to HAART Are Associated
with Increased Risk of Death and Poor Adherence to Therapy
HAART
improves survival dramatically
among HIV-positive individuals through its ability to reduce HIV
viral load to undetectable
levels and to increase the number of CD4+
T lymphocytes in peripheral blood.
However,
in observational studies of patients receiving HAART, only 40%
to 60% of patients develop significant reductions in HIV viral
load (VL) and significant increases in CD4 cell counts and between
12% and 23% have neither of these responses.
The
remaining patients see improvements in only 1 of immunologic or
virologic outcome. Although it is clear that those with concordant
positive responses (VL+/CD4+)
have generally favorable outcomes and that those with concordant
negative responses (VL-/CD4-)
have much worse outcomes, the prognostic significance of discordant
responses (VL+/CD4- or VL-/CD4+)
is not well understood.
To
clarify the significance of discordant immunologic and virologic
responses in treatment-naive individuals beginning protease
inhibitor (PI) or non
nucleoside reverse transcriptase inhibitor (NNRTI)-based
HAART, researchers at the University of British Columbia,
Vancouver,
British Columbia, Canada
undertook a study to examine the independent association of discordant
responses with non-accidental mortality. They then examined which
baseline characteristics were associated with these responses.
The 1527 participants in the present study were antiretroviral
naive and first received therapy containing 2 nucleosides and
a PI, a ritonavir-boosted
PI, or an NNRTI between August 1, 1996 and September
30, 2003. Participants must also have had at least 1 CD4 cell
count and plasma HIV-1 RNA measurement available between 3 and
9 months after starting HAART, conducted within 30 days.
Results
The authors conclude, “Discordant responses are independently
associated with an increased risk of mortality and are, in turn,
associated with poor adherence to therapy.”
Discussion
This
study demonstrated that both discordant immunologic and virologic
responses to therapy as determined 6 months after HAART initiation
are predictive of non-accidental mortality in treatment-naive
individuals, irrespective of whether therapy was PI or NNRTI based.
Previous studies had attributed this phenomenon to the use of
PIs but in the absence of NNRTI data.
“Furthermore,”
write the investigators, “we were unable to demonstrate significant
differences in mortality between the 2 discordant groups, a finding
supported by some previous studies but not by others.” In addition,
they note, “We have demonstrated the importance of adherence to
therapy in determining these discordant responses, a factor that
had not been examined previously.”
“In
conclusion,” note the researchers, “our work has demonstrated
that immunologic and virologic responses are important in determining
survival in patients receiving HAART. Failure to achieve treatment
thresholds in either category within 3 to 9 months after initiating
HAART is a significant predictor of later mortality.”
In
addition, adherence to therapy was found to be associated with
both of the discordant treatment responses. The authors conclude,
“Further research is needed to confirm these observations using
other data sets of treatment-naive individuals receiving PI- or
NNRTI-based therapy and to better define therapy response targets
that have clinical significance for these patients.”
From
the British Columbia Centre for Excellence in HIV/AIDS, Vancouver,
British Columbia, Canada; †Department of Health Care and Epidemiology,
Faculty of Medicine, University of British Columbia, Vancouver,
British Columbia, Canada; Department of Medicine, Faculty of Medicine,
University of British Columbia, Vancouver, British Columbia, Canada;
and Department of Social and Preventive Medicine, University of
Bern, Bern, Switzerland.”
11/02/05
Reference
D
M Moore and others. Discordant Immunologic and Virologic Responses
to Highly Active Antiretroviral Therapy Are Associated With Increased
Mortality and Poor Adherence to Therapy. Journal of Acquired Immune Deficiency Syndromes 40(3): 288-293.
November 1, 2005.
