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HIV-related Immune Suppression after ART Predicts Risk of Non-opportunistic Diseases: Results from the FIRST Study
Jason Baker*1,2, Jason Baker*1,2, G Peng1, J Rapkin1, D Abrams3, M Silverberg4, W Cavert1, R MacArthur5, W Henry1,2, W Henry1,2, J Neaton1, and Terry Beirn Community Prgms for Clin Res on AIDS (CPCRA)
1Univ of Minnesota, Minneapolis, US; 2Hennepin County Med Ctr, Minneapolis, MN, US; 3Univ of California, San Francisco, US; 4Kaiser Permanente, Oakland, CA, US; and 5Wayne State Univ, Detroit, MI, US
Background: Observational data suggest that the risk of
death from non-opportunistic diseases (OD) during HIV infection may be related
to immunosuppression. The SMART study showed that
episodic ART led to increased risk of cardiovascular (CV), renal, and liver
complications compared to continuous ART. The association of HIV-related immune
suppression with specific non-fatal and fatal non-OD events after ART has not
been well described. We compared the association between latest CD4 level
(prior to event) and non-OD events (liver, CV, renal, cancer) using follow-up
data from FIRST (substudy CPCRA 058).
Methods: In FIRST, ART-naïve patients were randomized
to 1 of 3 ART strategies (non-nucleoside reverse transcriptase inhibitors [NNRTI]
+ NRTI, protease inhibitors [PI] + NRTI, and 3-class therapy). Fatal and
non-fatal OD and non-OD events were collected over a 5-year median follow-up
and reviewed by an Endpoint Committee. OD events were defined by modified CDC
AIDS criteria. Non-OD events included: liver
(cirrhosis and grade 4 transaminitis); CV (myocardial
infarction, stroke, or coronary artery disease requiring surgery); renal (end-stage
renal disease or renal insufficiency); non-OD cancers (malignancy excluding non-Hodgkin’s
lymphoma and Kaposi’s sarcoma). Cox models examined the association of OD and
non-OD events with latest (time-updated) CD4 count (hazard ratio [HR] represent
the difference in risk for a 100 cell higher CD4 count).
Results: Of 1397 persons randomized in FIRST, median
entry CD4 was 163 cells/mL, with an average
increase of 238 cells/mL
during follow-up; CD4 changes and OD rates did not vary by treatment. Univariate and multivariate associations with latest CD4
levels are described (table). HR for non-OD events, combined and individually, indicate risk of event is reduced when CD4 count is higher.
|
Event
|
OD
|
Non-OD
|
Liver
|
CV
|
Renal
|
Non-OD
Cancer
|
|
#
of Events
|
226
|
166
|
86
|
21
|
38
|
32
|
|
Univariate HR/100
cells
95%CI
p-value
|
0.50
0.45,0.54
<0.01
|
0.79
0.74,0.84
<0.01
|
0.77
0.70,0.85
<0.01
|
0.86
0.72,1.02
0.08
|
0.76
0.66,0.88
<0.01
|
0.80
0.69,0.93
<0.01
|
|
*Multivariate HR/100
cells
95%CI
p-value
|
0.58
0.52,0.66
<0.01
|
0.81
0.73,0.89
<0.01
|
0.76
0.67,0.88
<0.01
|
0.78
0.61,1.01
0.06
|
0.92
0.76,1.11
0.40
|
0.83
0.66,1.03
0.08
|
|
*adjusted for:
age, sex, race, prior AIDS, hepatitis B and C, baseline CD4 & RNA,
and latest RNA
|
Conclusions: Higher, latest CD4 count was associated with
a reduced risk of non-OD events (liver, CV, renal, and cancer), though to a
lesser degree than with OD events. These data suggest that treatment strategies
minimizing the time spent at lower CD4 counts will prevent both non-OD and OD
events.
|
