Long‐Term Protease Inhibitor–Containing Therapy Results in Limited Improvement in T Cell Function but Not Restoration of Interleukin‐12 Production in Pediatric Patients with AIDS (original) (raw)
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Pediatrics, 2004
Objective.To evaluate 96-week clinical and immune outcomes to protease inhibitor–containing antiretroviral therapy. Methods.A prospective study was conducted of 40 human immunodeficiency virus (HIV)-infected children who displayed viral suppression (VS) with successful immune reconstitution (IS), failure to suppress virus (VF) or develop immune reconstitution (IF), or discordant immune and viral responses (VF/IS) at 24 weeks posttherapy. All children enrolled had viral RNA >4.0 log10 copies per mL and were Centers for Disease Control ad Prevention immune stage 2 or 3. Clinical, viral, and immune outcomes were assessed during the subsequent 72 weeks. Results.VS/IS and VF/IS groups displayed similar sustained increases in CD4 T cells, although viral levels rebounded by 48 and 96 weeks posttherapy to pretherapy levels in the discordant group. The VF/IS outcome group had significant increases in height and weight z scores compared with entry and were similar to the VS/IS group. After...
AIDS, 2008
Background-The goal of HAART is to promote reconstitution of CD4 + T cells and other immune responses. We evaluated the extent and the kinetics of immune reconstitution in HIVinfected children over 144 weeks of successful HAART. Methods-Thirty-seven children receiving their first HAART regimen had plasma HIV RNA; T cells and subpopulations; T-cell rearrangement excision circles (TREC) DNA; candida, HIV CD4 and HIV CD8 enzyme-linked immunospot measured at regular intervals. Results-Plasma HIV RNA became undetectable in 81% of patients at 24 weeks and remained undetectable in 77% at 144 weeks. In contrast, CD4 + % continuously increased. Distribution of Tcell subpopulations changed rapidly during the first 48 weeks of HAART and more slowly thereafter. At 144 weeks, total, naive and activated CD4 + % and naive CD8 + % of HIV-infected children were not significantly different from those of healthy age-matched controls, whereas total and activated CD8 + % remained elevated. CD4 + and CD8 + TREC content increased only during the first 48 weeks of HAART. They positively correlated with each other and with total CD4 + %, naive CD4 + % and naive CD8 + %. Candida and HIV CD4 enzyme-linked immunospot increased over time reaching peak values at 48 weeks and 144 weeks, respectively. HIV CD8 enzyme-linked immunospot decreased in magnitude over 144 weeks of HAART but retained its breadth. Baseline CD4 + % positively correlated with CD4 + % and with functional immune reconstitution at week 144, whereas baseline TREC correlated with TREC at week 144. Conclusion-HIV-infected children acquired normal distribution of CD4 + T cells and other subpopulations and recovered CD4-mediated HIV immunity after 144 weeks of HAART.
Aids Research and Human Retroviruses, 2002
In this study, we sought to characterize the T lymphocyte recovery in vertically HIV-1-infected children who respond to long-term highly active antiretroviral therapy (HAART). A 3-year longitudinal retrospective study was used to perform a cross-sectional study of 32 children rated according to the time course of CD4 1 T cell percentages in response to antiretroviral therapy and CDC clinical classification: (1) long-term asymptomatic (LTA group): 8 children in A1 during the whole follow-up period; (2) responsive to HAART (Rec group): 13 children in C3 before HAART who achieved CD4 1 T cell counts of .
The Pediatric Infectious Disease Journal, 2001
Background. Highly active antiretroviral therapy (HAART) has brought about rapid declines in HIV-1 RNA concentrations and an increase in CD4 ؉ counts in HIV-1-infected children. These changes are often accompanied by clinical improvement; however, the extent to which immune reconstitution occurs is not known. Design. We compared two cohorts (n ؍ 35) of HIV-1-infected children to evaluate the effects of HAART on immune recovery. Cohort 1 (C1) included clinically well children receiving HAART with a CD4 >22% at study initiation. Before HAART all children had moderately to severely suppressed immune function by CDC criteria (CD4 <25%) or CDC Category B or C disease. Cohort 2 (C2) included children with no current or past evidence of immunosuppression based on CDC criteria (CD4 >25%) and no evidence of clinical disease. Children in C2 were receiving a non-HAART regimen. Methods. Immunophenotyping was performed to characterize CD4 ؉ and CD8 ؉ subsets with regard to maturation and activation. T cell rearrangement excision circles (TRECs) were measured to quantify recent thymic emigrants. Results. No difference was found in percent CD4 ؉ or percent CD8 ؉ T cells or maturation markers between C1 and C2. There was significantly less expression of activation markers in both CD4 ؉ and CD8 ؉ cells in C1. There was no difference in TREC production between C1 and C2. Conclusion. Moderately to severely suppressed HIV-1-infected children receiving HAART are able to reconstitute their immune systems to a degree that is indistinguishable from that of stable, CDC Class A1 HIV-1-infected children with regard to CD4 ؉ and CD8 ؉ T cell subsets, expression of cellular maturation markers and TREC production.
Journal of Infectious Diseases, 2000
The response of 40 immunologic parameters was studied for 147 clinically stable, protease inhibitor-naive, human immunodeficiency virus (HIV)-infected children aged 2-17 years when antiretroviral therapy was changed to either a dual nucleoside analogue regimen or a protease inhibitor-containing regimen. Immunologic response to therapy, as measured by lymphocyte subsets, 3-color flow cytometric measures, and lymphoproliferative assays, were investigated for changes in weeks 44 and 48. The most significant changes after baseline that were associated with the administration of a protease inhibitor-containing regimen were seen for percentages of CD8 + /CD38 + /HLA-DR + , CD8 + /CD95 + /CD28 Ϫ , and CD8. The percentages of CD8 + /CD38 + / HLA-DR + and CD8 + /CD95 + /CD28 Ϫ decreased from baseline medians of 33% and 46% to medians of 18% and 30% at week 44 ( for both). Median CD4 cell count increased P ! .0001
The Journal of Infectious Diseases, 2005
We assessed CD4 cell recovery in 175 children with advanced human immunodeficiency virus disease who had received a 4drug antiretroviral regimen and were categorized as viral load (VL) responders (VLRs), partial VLRs, or non-VLRs. Median CD4 cell counts increased from baseline to week 48, and, among children with maximal follow-up, increases in CD4 cell counts were sustained to week 96 among VLRs and partial VLRs but not among non-VLRs. For VL rebounders still in the study, CD4 cell counts remained increased for 32 weeks after VL rebound. Sustained immunologic benefits can be achieved even with partial VL response in children with advanced disease.