696
Delayed Recovery of HIV-specific CD4-mediated Immunity in HIV-infected Children on their First HAART Regimen (PACTG P1021)
Adriana Weinberg*1, P Britto2, C Hu2, R Dickover3, J Patterson1, D Smith3, H Gutzman4, J Kraimer5, M Rathore6, R McKinney7, and PACTG P1021 Team
1Univ of Colorado Hlth Sci Ctr Sch of Med, Denver, US; 2Statistical & Data Analysis Ctr, Harvard Sch of Publ Hlth, Boston, MA, US; 3David Geffen Sch of Med, Univ of California, Los Angeles, US; 4Frontier Sci & Tech Res Fndn, Amherst, NY, US; 5Social & Sci Systems, Silver Spring, MD, US; 6Learning Resource Ctr, Univ of Florida Hlth Sci Ctr, Jacksonville, US; and 7Duke Univ Med Ctr, Durham, NC, US
Background: Effective ART reportedly
promotes recovery of immune functions with the exception of HIV-specific
immunity. We evaluated the changes of HIV-specific cell-mediated immunity and
nonspecific immune functions over 144 weeks of effective HAART in children
undergoing their first HAART regimen.
Methods: A total of 37 ART-naive children, 3 to 21
years of age (median=10.5), who initiated didanosine
(ddI), emtricitabine (FTC),
and efavirenz (EFV) were tested at weeks 0, 24, 48,
and 144 by ELISpot using HIV-inactivated whole virion to estimate CD4-mediated responses; 7 HIV peptide
pools to estimate CD8-mediated responses and Candida, and by T cell immunophenotyping
and CD4- and CD8-specific TREC measurement.
Results: The table shows that HIV-infected children
controlled HIV replication and increased CD4 cells after ≤24 weeks of
HAART. TREC, naive and memory CD4 cells, and Candida cell-mediated immunity improved during the first year of
HAART and remained stable thereafter. In contrast, total CD4 and naive CD8
cells continued to increase; and activated CD4 and CD8, memory CD8 cells, and
CD8-mediated HIV-specific cell-mediated immunity continued to decrease until
144 weeks. Reconstitution of CD4-mediated HIV-specific cell-mediated immunity
was first observed at week 144 and was positively associated with naive and
central memory CD4 and negatively associated with activated CD8 cells.
Conclusions: During the first year of effective HAART, immunologic
abnormalities associated with HIV infection persist in the absence of viral
replication measured by plasma HIV RNA. However, immune functions continue to
improve over ≥3 years of HAART. It is critical to determine the
mechanisms responsible for the late HAART-associated immunologic improvement
and the clinical benefit that may derive from it.
|
Outcome
variable (median)
|
Baseline [37]
|
Week 24 [34]
|
Week 48 [31]
|
Week 144
[29]
|
|
HIV plasma RNA (copies/mL)
|
47,775
|
<50
|
<50
|
<50
|
|
CD4 cells (%)
|
17
|
28
|
33
|
37
|
|
CD4 TREC (log 10 copies/106 cells)
|
4.0
|
4.7
|
4.7
|
4.7
|
|
CD8 TREC (log 10 copies/106 cells)
|
3.7
|
4.5
|
4.5
|
4.6
|
|
CD4+CD45RA+CD62L+ naive (%)
|
54
|
60
|
61
|
61
|
|
CD4+ CD45RA– memory (%)
|
47
|
40
|
39
|
40
|
|
CD4+CD38+HLADR+ activated (%)
|
17
|
8
|
6
|
4
|
|
CD8+CD45RA+CD62L+ naive (%)
|
30
|
48
|
52
|
57
|
|
CD8+CD45RA– memory (%)
|
70
|
52
|
48
|
44
|
|
CD8+CD38+HLADR+ activated (%)
|
53
|
28
|
22
|
14
|
|
CD4 HIV cell-mediated immunity (SFC/106 PBMC)
|
5
|
8
|
11
|
35
|
|
CD8 HIV cell-mediated immunity (SFC/106 PBMC)
|
1074
|
1164
|
691
|
259
|
|
CD8 HIV cell-mediated immunity breadth (N recognized/N tested peptide
pools)
|
1.0
|
1.0
|
0.85
|
0.85
|
|
Candida
cell-mediated immunity (SFC/106 PBMC)
|
8
|
12
|
32
|
41
|
Brackets indicate N subjects on study; boldface indicates p <0.05 compared to baseline;
underline indicates p <0.05
compared to week 48.
|
