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Effect of azidothymidine (AZT) on T lymphocyte activation marker in patients with aids-related complex
907
highly significant reduction of the mean PECs Percentage when each was given with or after antigen. Hydrocortisone produced more significant inhibition than the test drugs.
References Fabey, J.L. and McKelvey, E.M. (1965), J. Immunol. 94.46. Fauci, AS. and Pratt, K.R. (1976). J. Bxp. Med. 144, 674. Mansini. G., Caibonara. A.O. and Hermans, J.F. (1965) Immunochemistry, 2.235.
I
P.tu.250
Effect of azidothymidine (A
yte activation marker i
Levacher, M., Rouveix, B. and Pocidalo, J.J. D@nrtement de Pharmacologic, INSERM LJl3, Hcipital Claude-Bernard, 10 avenue de la Porte d’Aubervil1ier.s75019 Paris, France
In addition to reductions in the percentage and absolute number of CD4+ lymphocytes, abnormally high levels of activated peripheral T lymphocytes (CD3+HLA-DR+ phenotype) 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 AZT. All patients showed two or more features of CDC groups IVA and C2 (Centers for Disease Control, 1986). AZT therapy was initiated with 200 mg orally every 4 hours. Thereafter, dosages depended on tolerance. Blood samples were obtained before starting AZT therapy, then after 12 and 24 weeks. Two-color immunophenotyping of peripheral blood lymphocytes and flow cytometric analysis by a FACScan cytometer were performed. The statistical significance of changes in lymphocyte subsets was assessed using the Wilcoxon matched-pairs signed-rank test. A striking fall in the proportion of activated T lymphocytes from baseline was observed (P c 0.001) at week 24. In contrast, the percentage of CD4+ cells showed a slight and transient rise at week 12 (P -z 0.05). Of the 34 patients, 11 developed AIDS, while 23 remained AIDS-free during 51 weeks of follow-up. Similar patterns of change in CD4+ and HLA-DR+CD3+ lymphocytes occurred in the AIDS progressors and nonprogressors. Although changes in CD4” cells 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 and a greater proportion of activated T lymphocytes. Because CD4 enumeration has become common practice, less attention has been paid to other lymphocyte subsets. Studies are underway to determine if therapeutic intervention is beneficial in asymptomatic HIV-infected individuals. However, many of these patients lack usual AIDS risk markers, i.e. CD4+ lymphocyte depletion, high levels of serum fl2-microgobulin or detectable HIV p24 antigen (Moss et al., 1988). Alternative indicators will therefore be required for early intervention trials. Our results concerning advanced ARC patients favour further investigations to determine if enumeration of activated T lymphocytes should be added to the conventional lymphocyte-phenotype monitoring panel (CD4, CDS) in HIV-infected subjects at earlier stages of the disease.
References Centers for Disease Contrcl, 1986, Classiftcation system of human T-lymphotropic virus type lII/lymphadenopathy-associated
virus infections, Ann. Intern. Med. 105, 234. Moss, A.R., P. Bacchetti, D. Osmond, W. Krampf, R.E. Chaisson, D. Stites, J. Wilber. J.P. Allain and J. Carlson. 1988. Seropositivity for HIV and the development of AIDS or AIDS-related condition: three year follow-up of the San Francisco General Hospital Cohort, Br. Med. J. 296, 745.
highly significant reduction of the mean PECs Percentage when each was given with or after antigen. Hydrocortisone produced more significant inhibition than the test drugs.
References Fabey, J.L. and McKelvey, E.M. (1965), J. Immunol. 94.46. Fauci, AS. and Pratt, K.R. (1976). J. Bxp. Med. 144, 674. Mansini. G., Caibonara. A.O. and Hermans, J.F. (1965) Immunochemistry, 2.235.
I
P.tu.250
Effect of azidothymidine (A
yte activation marker i
Levacher, M., Rouveix, B. and Pocidalo, J.J. D@nrtement de Pharmacologic, INSERM LJl3, Hcipital Claude-Bernard, 10 avenue de la Porte d’Aubervil1ier.s75019 Paris, France
In addition to reductions in the percentage and absolute number of CD4+ lymphocytes, abnormally high levels of activated peripheral T lymphocytes (CD3+HLA-DR+ phenotype) 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 AZT. All patients showed two or more features of CDC groups IVA and C2 (Centers for Disease Control, 1986). AZT therapy was initiated with 200 mg orally every 4 hours. Thereafter, dosages depended on tolerance. Blood samples were obtained before starting AZT therapy, then after 12 and 24 weeks. Two-color immunophenotyping of peripheral blood lymphocytes and flow cytometric analysis by a FACScan cytometer were performed. The statistical significance of changes in lymphocyte subsets was assessed using the Wilcoxon matched-pairs signed-rank test. A striking fall in the proportion of activated T lymphocytes from baseline was observed (P c 0.001) at week 24. In contrast, the percentage of CD4+ cells showed a slight and transient rise at week 12 (P -z 0.05). Of the 34 patients, 11 developed AIDS, while 23 remained AIDS-free during 51 weeks of follow-up. Similar patterns of change in CD4+ and HLA-DR+CD3+ lymphocytes occurred in the AIDS progressors and nonprogressors. Although changes in CD4” cells 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 and a greater proportion of activated T lymphocytes. Because CD4 enumeration has become common practice, less attention has been paid to other lymphocyte subsets. Studies are underway to determine if therapeutic intervention is beneficial in asymptomatic HIV-infected individuals. However, many of these patients lack usual AIDS risk markers, i.e. CD4+ lymphocyte depletion, high levels of serum fl2-microgobulin or detectable HIV p24 antigen (Moss et al., 1988). Alternative indicators will therefore be required for early intervention trials. Our results concerning advanced ARC patients favour further investigations to determine if enumeration of activated T lymphocytes should be added to the conventional lymphocyte-phenotype monitoring panel (CD4, CDS) in HIV-infected subjects at earlier stages of the disease.
References Centers for Disease Contrcl, 1986, Classiftcation system of human T-lymphotropic virus type lII/lymphadenopathy-associated
virus infections, Ann. Intern. Med. 105, 234. Moss, A.R., P. Bacchetti, D. Osmond, W. Krampf, R.E. Chaisson, D. Stites, J. Wilber. J.P. Allain and J. Carlson. 1988. Seropositivity for HIV and the development of AIDS or AIDS-related condition: three year follow-up of the San Francisco General Hospital Cohort, Br. Med. J. 296, 745.