Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure.
To analyse the effect of highly active antiretroviral therapy (HAART) on T-lymphocyte functions we selected seven HIV-1 perinatally infected children (CDC immunological category 1 or 2) who had neither a fall in their plasma HIV-1 RNA levels nor a significant rise in CD4+ lymphocyte counts while receiving HAART. Clinical signs and symptoms were monitored monthly. Plasma viral load, CD4+, CD8+, CD19+ lymphocyte counts and in vitro T-lymphocyte proliferative responses to mitogens (anti-CD3, phytohaemoagglutinin, concanavalin A and pokeweed mitogen) and recall antigens (Candida albicans and tetanus toxoid) were tested at baseline and after 1, 3, 6 and 12 months of HAART. Twenty-two healthy age-matched children were studied as controls. A gain in body weight, no worsening of the disease and no recurrence of opportunistic infections were observed. At baseline, the majority of the children had low responses to mitogens, and all of them had a defective in vitro antigen-specific T-lymphocyte response (<2 standard deviations below the mean result for controls). During HAART, a significant increase in the response to mitogens and antigens was observed in all the patients. The T-lymphocyte response was restored more consistently against antigens to which the immune system is constantly exposed (Candida albicans, baseline versus 12 months: P < 0.001) compared with a low-exposure antigen (tetanus toxoid, baseline versus 12 months: P < 0.01). HAART restores in vitro T-lymphocyte responses even in the absence of a significant viral load decrease and despite any significant increase in CD4+ lymphocyte counts. It implies that a direct mechanism might be involved in the overall immune recovery under HAART.
Peruzzi
M
M
Laboratory of Immunology, Department of Paediatrics, University of Florence, Italy. maurizio.demartino@unifi.it
Azzari
C
C
Galli
L
L
Vierucci
A
A
De Martino
M
M
D000293:Adolescent; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018941:Antigens, CD19 / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D005260:Female; D015658:HIV Infections / Q000151:congenital / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007109:Immunity; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D019380:Anti-HIV Agents; D018941:Antigens, CD19; D015704:CD4 Antigens; D016827:CD8 Antigens; D008934:Mitogens