738 
Effect of HAART Interruption on Plasma Inflammatory Markers Associated with Cardiovascular Disease. 24-Month Results from a Randomized Study
Montserrat Olmo*1, C Alonso-Villaverde2, M Peñaranda3, F Gutierrez4, J Romeu5, M Larrousse6, P Domingo7, J Oteo8, J Curto1, D Podzamczer1, and STOPAR Study Team
1Hospital de Bellvitge, Barcelona, Spain; 2Hospital de Reus, Tarragona, Spain; 3Hospital Son Dureta, Mallorca, Spain; 4Hospital de Elche, Alicante, Spain; 5Hospital Trias i Pujol, Barcelona, Spain; 6Hosp Clin i Provincial, Barcelona, Spain; 7Hospital de Sant Pau i la Santa Creu, Barcelona, Spain; and 8Hosp de La Rioja, Logrono, Spain
Background: HAART interruption has been associated
with an increase in cardiovascular risk. We analyzed the influence of
CD4-guided HAART interruption on inflammatory markers associated with cardiovascular
disease (CVD).
Methods: This was a sub-study of a randomized,
multicenter, 36-month completed trial. HIV+ adults with undetectable
viral load >6 months, CD4 >500, and CD4 nadir >100, receiving mainly
NNRTI regimens, were allocated to therapy continuation or to therapy
interruption. Interleukin (IL) -6, IL-8, macrophage chemotactic protein-1 (MCP-1),
sVCAM-1, sCD40L, sP-selectin, and t-PA were measured by a multiplex cytometric bead-based assay (FlowCytomix
Multiplex; BenderMedsystems; Austria) at baseline, and months 12, 24, and 36. Therapy-interruption
patients with at least 70% time off HAART during the study period were
analyzed. Data are presented as percentage of change from baseline and median
values at each time point; 24-month results are presented.
Results: We included 77 eligible patients (44 therapy
continuation, 33 therapy interruption). Groups were comparable for baseline
characteristics: 77.9% men, median age 41 years, 36.4%
homosexual, 32.5% former drug users, 6.5% AIDS, CD4 846 cells/mm3,
total cholesterol/HDL-c/ LDL-c 5.1/1.3/3 mmol/L, triglycerides 1.7 mmol/L,
glucose 5.1 mmol/L, and 83.1% NNRTI-based HAART. MCP-1 and sV-CAM-1 increased
from baseline to month 12 and 24 only in therapy-interruption group. MCP-1
ranged from 255.5 pg/mL to 397 (p <0.001) at month 12 and 358.1 (p
<0.002) at month 24. sV-CAM-1 ranged from 4052.5 ng/mL to 4833.8 (p <0.001)
and 4706.5 (p =0.011), respectively. The percentage of change by
treatment arm is shown in Figures 1 and 2; significant differences between therapy
interruption and therapy continuation are evident at month 12. IL-6 increased
from baseline to months 12 and 24 in therapy interruption group (p = 0.008
and p <0.001, respectively) and decreased in the therapy-continuation
group (p <0.001 and p <0.001, respectively), with a trend
to a significant difference between groups at month 12 (p = 0.063). No
significant changes were observed in IL-8, sP-selectin, t-PA, or sCD40L. When
only patients off HAART throughout the study period were considered for
analysis, all the preceding results were confirmed.
Conclusions: Patients with viral replication due to
HAART interruption presented elevated inflammatory markers
(MCP-1, sVCAM-1, and IL-6) after 24 months when compared to
those under viral control. As these cytokines correlate with endothelial damage
and development of atherosclerotic plaque, our data may partially explain the
harmful cardiovascular effect of HAART interruption.
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