698
T-cell Phenotypes and Responses to Vaccines in Severely Immunocompromised HIV-infected Children Initiating HAART in PACTG 1006
Adriana Weinberg*1, M Rigaud2, P Muresan3, P LaRussa4, J Kraimer5, P Jean-Philippe6, J Read7, W Borkowsky8, and PACTG 1006 Team
1Univ of Colorado Hlth Sci Ctr Sch of Med, Denver, US; 2New York Univ Med Ctr, NY, US; 3Statistical & Data Analysis Ctr, Harvard Sch of Publ Hlth, Boston, MA, US; 4Columbia Univ Coll of Physicians and Surgeons, New York, NY, US; 5Social & Sci Systems, Silver Spring, MD, US; 6NIH, Bethesda, MD, US; 7Natl Inst of Child Hlth and Human Devt, NIH, Bethesda, MD, US; and 8New York Univ Sch of Med, NY, US
Background: Naive and memory CD4 cells increase in
HIV-infected individuals on HAART. To determine the kinetics of reconstitution
of different CD4 types and their correlations with responses to vaccines, data
from Pediatric AIDS Clinical Trials Group (PACTG) 1006 subjects were analyzed.
Methods: Severely immunocompromised
children (CD4 <15%) who demonstrated a reduction of >0.75 log in plasma
HIV RNA within 4 weeks of initiating HAART sequentially received 3 doses of
tetanus toxoid (TT) recall antigen and of hepatitis (HepA)
vaccine neoantigen, at weeks 8, 16, 24, 32, 40, and 48. Cell- and
humoral-mediated immunity were measured by lymphocyte
proliferation (LPA) and ELISA, respectively.
Results: Data from 35 subjects whose median age was 13 years were analyzed.
The table shows that median plasma HIV RNA decreased and CD3 cells increased until
week 24 and then stabilized; CD4 cells increased until week 48; naive and
memory CD4% increased until week 24 only, whereas absolute numbers continued to
rise until week 48.
At entry, 65, 6, 8, and 6%
subjects had positive TT serology, LPA, HepA serology, and LPA, respectively. The
respective proportions of responders, 4 weeks after the last dose of the
vaccine, were 90, 69, 65, and 12%. Correlation analyses showed that TT LPA and
TT and HepA antibody responses correlated with CD4% and memory CD4 counts (p <0.05). TT LPA responses also
correlated with naive CD4% and counts (p
<0.05). HIV RNA was inversely correlated with TT LPA and antibody (p <0.05) but not with HepA responses.
conclusions: In this highly immunocompromised
and often ART-experienced population, the percentage of CD4 cells classified as
neither naive nor memory was high at baseline and decreased with time on HAART.
Responses to recall and neoantigens were indiscriminately associated with
memory and naive CD4 cell numbers, which peaked after 48 weeks of HAART. This
suggests that the immunogenicity of new and recall vaccines may be improved by
their administration after the first year of HAART.
|
Outcome variable (median)
|
Entry
[27-35]
|
Week 24
[24-34]
|
Week 48
[27-35]
|
Week 100
[23-26]
|
|
Log HIV
plasma RNA
|
4.9
|
2.6
|
2.6
|
2.7
|
|
CD4%
|
7
|
14
|
18
|
19
|
|
CD4 cells/µL
|
84
|
279
|
434
|
460
|
|
CD3%
|
30
|
44
|
39
|
44
|
|
CD3 cells/µL
|
1326
|
2418
|
2356
|
2535
|
|
CD4+CD45RA+CD62L+
naive%
|
29
|
51
|
57
|
51
|
|
CD4+CD45RA+CD62L+
cells/µL
|
18
|
152
|
196
|
172
|
|
CD3+CD4+CD45RO+
memory%
|
6
|
9
|
11
|
12
|
|
CD3+CD4+CD45RO+ cells/µL
|
7
|
24
|
53
|
46
|
Brackets indicate n subjects
contributing data; boldface indicates p
<0.05 compared to baseline; underline indicates p <0.05 compared to week 24.
|
