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The Effect of ART on T-cell Activation in HIV-infected Persons with TB and CD4 Lymphocyte Counts >350 cells/mm3 in Uganda
Charles Mahan*1, H Kayanja1, M Walusimbi2, R Mugerwa2, D Havlir3, C Whalen1, H Boom1, H Mayanja2, and Uganda-CWRU Research Collaboration
1Case Western Reserve Univ, Cleveland, OH, US; 2Makerere Univ, Kampala, Uganda; and 3Univ of California, San Francisco, US
Background: Elevated markers of immune activation (CD38+)
on CD8 T cells are associated with a poor response to ART. Active tuberculosis
(TB) is associated with generalized immune activation and may affect HIV
disease progression, most markedly among those persons with CD4 >200
cells/mm3. We report data from an immunology sub-study of a
randomized, prospective trial of punctuated ART in HIV/TB-co-infected patients.
Methods: ART-naïve persons with smear-positive
pulmonary TB and CD4 counts >350 cells/mm3 were started on a 6-month
course of zidovudine (ZDV) + lamivudine
(3TC) + abacavir (ABC) within 1 month of beginning
standard TB drug therapy. HIV RNA and CD4 counts were obtained at baseline, 3
months, and 6 months. Flow cytometry analysis for
CD38, and CD45RO on CD4 and CD8 T cells was also performed. Statistical
analysis of longitudinal data was done by Wilcoxon
rank test.
Results: In a
cross-sectional analysis of 34 persons (n
= 21 at baseline, n = 12 at 3 months,
n = 8 at 6 months) treated with
combined HIV/TB therapy, viral suppression was achieved as measured by HIV RNA
level <400 copies/mL in 66% (8 of 12) at 3 months
and 88% (7 of 8) achieved viral suppression at 6 months. CD4 T cell counts increased from baseline to
6 months by an average of 63 cells/mm3.
Comparing immune activation parameters between baseline and 6 months, we found
the following: CD38-expressing CD4 T
cells did not decline (p = 0.36 at 6
months). In contrast, total CD8CD38+ percentages showed a
significant decline that was evident at both 1 month and 6 months (p = 0.04 and 0.006). In addition,
expression of CD38 in the CD8CD45RO+ (memory cell) compartment
showed a significant decline by month 2, which persisted through month 6 (p = 0.01). CD8CD38+
percentage and CD8CD45RO+CD38+ percentage correlated with
HIV RNA viral load (p = 0.05 and
0.02).
Conclusions: Starting ART soon after TB therapy in persons
with early HIV (CD4 counts >350 cells/mm3 ) results in a rapid
decrease in HIV-associated markers of immune activation as measured by CD38+
percentage in the CD8 T cell and CD8 memory T-cell subset (CD45RO+).
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