M. Kharbanda et al., Patterns of CD8 T cell clonal dominance in response to change in antiretroviral therapy in HIV-infected children, AIDS, 14(15), 2000, pp. 2229-2238
Objective: To examine the influence of change in antiretroviral therapy (AR
T) on patterns of CD8 T cell clonal dominance in HIV-infected children.
Design: Seventeen HIV-infected children with plasma virus loads between 3.1
and 5.7 log(10) were investigated before and after changes in ART.
Methods: CDR3 spectratyping was performed in 22 T cell receptor (TCR) V bet
a subfamilies by multiplex polymerase chain reaction (PCR) in purified peri
pheral blood CD8 T cells in conjunction with CD4 cell counts, plasma HIV-RN
A copies and lymphoproliferative assays (LPA).
Results: CD8 T cell clonal dominance in two or more V beta families was pre
sent in eight out of 17 children. After a change in therapy, 13 patients (7
6%) acquired new clones whereas three patients (17.6%) showed a loss in CD8
cell clones. An increase in the numbers of dominant clones correlated with
an increase in percentage CD4 cell counts (P < 0.001) and with improved LP
A responses to tetanus (P < 0.05) and alloantigens (P < 0.01). CD4 cell inc
rease was associated with an initial mean gain of 3.1 +/- 2.1 CD8 cell clon
es, independent of a virological response. A loss of CD8 cell clones or fai
lure to achieve CD4 T cell increase was associated with failure to achieve
virological suppression.
Conclusion: Children with chronic HIV infection manifest CD8 T cell clonal
dominance, which appears to be dependent upon the adequacy of the CD4 cells
. With optimization of therapy, a gain in clonal dominance is the predomina
nt response, except in situations of failure to contain viral replication.
(C) 2000 Lippincott Williams & Wilkins.