T activation marker evaluation in ARC patients treated with AZT. Comparison with CD4+ lymphocyte count in non-progressors and progressors towards AIDS.
Reductions in the percentage and absolute number of CD4+ lymphocytes, as well as abnormally high levels of activated peripheral T lymphocytes (CD3+ HLA-DR+ phenotype) and an increased proportion of CD8+ cells coexpressing the CD57 surface antigen (involved in natural killer activity) have been reported in HIV infection and associated with disease progression. We prospectively measured these subsets of lymphocytes in 34 patients with advanced AIDS-related complex (ARC) treated with azidothymidine (AZT). Peripheral blood lymphocyte phenotyping was performed before treatment, then at weeks 12 and 24. A striking fall in the proportion of activated T lymphocytes from baseline was observed (P less than 0.001) at week 24. In contrast, the percentage of CD4+ cells showed a slight and transient rise at week 12 (P less than 0.05). No modification in levels of CD8+ or CD8+ CD57+ cells was detected during the study. Of the 34 patients, 11 developed AIDS, and 23 remained AIDS-free during 51 weeks of follow-up. Similar patterns of change in CD4+ and HLA-DR+ CD3+ lymphocytes were found in the AIDS progressors and nonprogressors. Likewise, HIV p24 antigenaemia showed parallel decreases in both groups of patients. Although changes in CD4+ cells, p24 antigenaemia and HLA-DR-reactive T lymphocytes were not predictive of clinical outcome, large differences existed between the two groups prior to the initiation of therapy. The short-term onset of AIDS was associated with lower CD4+ cell numbers, higher levels of serum p24 antigen and a greater proportion of activated T lymphocytes. Our results suggest that the possible interest of T lymphocyte activation markers, in conjunction with conventional phenotyping, should be investigated further.
Pharmacology Laboratory, INSERM U13, Hôpital Claude Bernard, Paris, France.
M
M
Levacher
S
S
Tallet
M C
MC
Dazza
E
E
Dournon
B
B
Rouveix
J J
JJ
Pocidalo
D000386:AIDS-Related Complex / Q000188:drug therapy* / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D015704:CD4 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018959:CD57 Antigens; D016827:CD8 Antigens; D015331:Cohort Studies; D005260:Female; D015683:Gene Products, gag / Q000097:blood; D016655:HIV Core Protein p24; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010641:Phenotype; D011446:Prospective Studies; D011897:Random Allocation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014758:Viral Core Proteins / Q000097:blood; D015215:Zidovudine / Q000627:therapeutic use*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D018959:CD57 Antigens; D016827:CD8 Antigens; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell; D014758:Viral Core Proteins; D015215:Zidovudine