| |
Influence of Disease Progression and Response to Antiretroviral Therapy (ART) on CD4 T Cell Repertoire in HIV-Infected Children M. KHARBANDA*, M. SUN, V. CHITNIS, S. BAKSHI, and S. PAHWA.
North Shore Univ. Hosp., New York Univ. Sch. of Med., Manhasset Rationale: CD4 T cells in HIV-infected children often show a marked improvement with antiretroviral therapy but their relationship to the immune repertoire is not clearly defined. This study was aimed at investigating CD4 T cell V repertoire in HIV-infected children in relation to disease severity and their response to ART.
Methods: 25 HIV-infected children with an age range 2.4-18.9 yr. (mean ± SD 9.7 ± 4.3yr.), who were on ART with 2 drugs (n=7) or >3 drugs (n=18) drugs were studied. 11 children were in immune category 1 (IC1, CD4%>25), 9 in IC2 (CD4% 15-24) and 5 were in IC3 (CD4% <15). Plasma virus load range was 2.6-5.8 log10 HIV RNA copies/ml. TCR V repertoire was determined by CDR3 length spectratyping using multiplex PCR in purified CD4 T cells and compared to cord blood CD4 TCR V repertoire for percent skewing.
Results: CD4 TCR V repertoire was significantly perturbed in HIV-infected children with V families 4, 21, 23 and 24 most frequently affected. Patients in IC3 exhibited greater skewing of their CD4 V repertoire (29.1%) compared to patients in IC1 (11.8%, p<0.001) and IC2 (10.6%, p<0.003). Patients with undetectable virus load (<400 HIV RNA copies/ml, n=6) demonstrated less skewing as compared to patients with detectable virus (mean log10 4.6 HIV RNA copies/ml; p<0.05). 7 patients with poorly controlled disease changed treatment and showed a virologic response (decrease of >1.5 log10) and immunologic response (increase of >10% in CD4 cell). CD4 TCR V skewing decreased in 4 of these 7 patients. Patients who did not change treatment (n=7) were re-analyzed at a mean interval of 6 months. A further decrease in skewing of CD4 V repertoire was noted in those patients who maintained a stable immunologic and virologic response.
Conclusions: In HIV-infected children, CD4 TCR V repertoire disruptions are widely prevalent in patients with low CD4 T cells or high viral load. Normalization of CD4 T cell repertoire is dependent upon increase in CD4 T cells in association with complete or partial virologic suppression in response to ART.
Key Words: CD4 Vbeta repertoire, HIV in children, Immune response
|
