Continuous improvement in the immune system of HIV-infected children on prolonged antiretroviral therapy

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 HIV-infected 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 T-cell 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. HIVCD8 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. (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins