PREDICTOR OF THE RATE OF CD4 LYMPHOCYTE LOSS IN HIV-1-SEROPOSITIVE ASYMPTOMATIC HEMOPHILIACS BY IN-VITRO IMMUNOGLOBULIN-SYNTHESIS

The objective of the present study was to evaluate the prognostic util ity in determining the risk of AIDS progression in HIV-1-infected asym ptomatic hemophiliacs by in vitro immunoglobulin (Ig) synthesis. With this aim, a cohort of 28 HIV-1-seropositive hemophiliacs were studied. All showed the number of CD4 lymphocytes higher than 400 positive cel ls/mm(3). In all cases the spontaneous and pokeweed mitogen-induced in vitro production of Ig by peripheral blood lymphocytes was evaluated at the beginning of the study and the ratio stimulated/spontaneous (St im/Spon) synthesis was calculated. At the same time, the absolute CD8( +) cell count, IgA serum immunoglobulin, p24 HIV-1 antigenemia, and be ta(2) microglobulin were calculated. These data were monitored during the 4-year follow-up of patients and compared with the stimulated/spon taneous Ig synthesis ratio to evaluate the predictive significance on the progression of HIV infection. According to the stimulated/spontane ous Ig synthesis ratio, hemophilic patients were separated into two ca tegories. Group I included 12 subjects with a Stim/Spon ratio higher t han 2 (the lowest value of normal controls) and group II included 16 c ases with a ratio lower than 2. As control, in 36 HIV-1-negative hemop hiliac individuals the stimulated/spontaneous Ig ratio ranged between 2 and 42; mean +/- SEM, 12.9 +/- 1.8. At the end of the 4-year follow- up, group I patients showed a CD4 count and clinical staging consisten t with those of the first evaluation; in contrast group II demonstrate d a significant decrease in CD4 lymphocytes and deterioration of clini cal conditions. Our results show that a low Stim/Spon Ig ratio when th e CD4 lymphocyte count was still normal appears to predict the depleti on of this lymphoid subset and progression to AIDS before T CD8, IgA i mmunoglobulin, p24 HIV-1 antigenemia, and beta(2) microglobulin abnorm alities. In this setting, the stimulated/spontaneous Ig ratio may repr esent a useful tool for clinical decisions in HIV-1-infected hemophili acs. (C) 1996 Academic Press, Inc.