Alterations in the circadian time structure of the secretion of several hormones were investigated in 13 male patients infected with human immunodeficiency virus (HIV). Seven were asymptomatic (classified CDC II, according to the criteria of the Atlanta Centers for Disease Control), and 6 had acquired immunodeficiency syndrome (CDC IV). Ten healthy males volunteered as controls. Plasma levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), cortisol, testosterone, ACTH, and beta-endorphin were determined by RIA in blood samples obtained every 4 h from 0830-0830 h the next morning. Data were analyzed both by two-way analysis of variance and the cosinor method. Circadian rhythms were statistically validated for each of the six hormones in each of the three groups of subjects. Compared with the control subjects, mesors (24-h adjusted means) were significantly higher for cortisol and lower for DHEA, DHEA-S, and ACTH (P less than 0.001 for all four hormones) in all HIV-infected patients. Plasma testosterone mesors were similar in controls and CDC II patients, but decreased significantly in the CDC IV patient group (P less than 0.05). Analysis of the circadian rhythms of plasma hormone levels clearly indicated an altered adrenal hormonal state in HIV-infected male patients, even during the asymptomatic period of the infection. For instance, plasma cortisol at 0430 h was more than twice as high in HIV-infected patients as it was in time-qualified controls. Although patients already had elevated plasma cortisol and lowered adrenal androgen levels at this stage, hypogonadism was not observed, as gauged by plasma testosterone concentrations. We speculate that the primary hormonal defect in HIV-infected patients is increased cortisol secretion resulting from circadian-varying stimulation of the adrenal cortex by a factor other than pituitary ACTH. This factor might be a stimulating substance secreted primarily by infected immune cells. Excess cortisol would lower adrenal androgen secretion by shifting adrenal steroid biosynthesis toward glucocorticoids and decreasing pituitary ACTH secretion via a negative feedback mechanism.

Natural killer (NK) cell-related phenotypes were analyzed in human immunodeficiency virus (HIV) infection. Our study involved 168 HIV-infected patients (72 CDC Stage II, 48 Stage III, and 46 Stage IV) and 60 healthy individuals. Analyses were conducted using flow cytometry and monoclonal antibodies. In comparison to the control group, all patient groups showed a significant decrease (p less than 0.001) of the CD16+ and CD16+CD3- phenotypes; furthermore, the comparison among patient groups showed no significant difference. It seems, therefore, that the decrease begins in the asymptomatic stage (CDC II) and remains constant during the infection. CD16+ NK cells were further divided into two subsets: CD16+CD8+ and CD16+CD8-. This subdivision shows a severe selective depletion of the CD16+CD8+ subset, but not in the CD16+CD8- subset. The depletion of the CD16+CD8+ subset also appears in the CDC asymptomatic stage and remains constant in CDC stages III and IV. Elsewhere, we observed that CD16+CD8+ lymphocytes are CD3-; complementary analysis of CD3-CD8+ cells showed a depletion comparable to that of the CD16+CD8+ phenotype. Depletion of the CD3-CD8+ subset, which belongs to the NK cell compartment, was observed although the total CD8 population showed a statistically significant increase. We conclude that, in HIV infection, there is a quantitative decrease of the NK CD16+ cell population, which appears to be due to a selective depletion of the CD16+CD8+CD3- compartment. This severe depletion appears to begin early in the infection.

To assess the place of passive immunotherapy in the treatment of AIDS, a randomized study was conducted that evaluated the safety and short-term efficacy of serial transfusions of human immunodeficiency virus type 1 (HIV-1) seropositive plasma in 18 patients. Heat-inactivated anti-HIV antibody-rich plasma was compared with seronegative fresh-frozen seronegative plasma given in addition to zidovudine and other conventional prophylactic treatments. Seven transfusions every 2 weeks of immune plasma significantly reduced (2 vs. 8, P = .016) the number of opportunistic infections. Antigenemia became undetectable. When transfusions were stopped, positive p24 antigenemia returned at a level higher than before treatment and was correlated with a severe clinical deterioration, suggesting a rebound effect. This trial suggests that passive immunotherapy is promising in AIDS treatment. It confirms also that plasma donation does not affect donors' CD4 cell count over a 1-year period. In patients with severe immunodeficiency, special attention should be paid to withdrawal of an effective therapy as virologic relapse may be explosive and poorly tolerated.

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No difference in HLA-A, B or DR gene frequencies could be observed between 172 control subjects and 180 HIV-1-seropositive subjects of European ancestry diagnosed through the systematic screening of blood donations. In contrast, progression to acquired immune deficiency syndrome (AIDS; 21 patients) or CD4 lymphocyte loss equal or more than 20% over a 6-month period (37 subjects) was found to be associated with the B8DR3 haplotype (relative risk = 10.64, p < 0.003, and 2.23, p < 0.092, respectively). Other independently significant associations assessed through the multivariate Cox proportional-hazards model were B16, BW21 and B35 alleles as factors of bad prognosis. Conversely, A1 and DR4 alleles were factors favouring longer survival.

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43 adults from a renal dialysis unit staff have received regularly spaced gamma-globulin administrations for hepatitis B prophylaxis. Several blood samples were collected over a prolonged period of time (160 days). Following gamma-globulin administration, anti-immunoglobulin antibodies of the IgE class were detected in 80% of this population, a fortnight after the first injection using serum absorptions on polymerized gamma-globulins or a specific inverse RAST method. The reactivity pattern of these IgE anti-immunoglobulin antibodies was similar to that observed for the anti-immunoglobulin antibodies with "limited specificity" detected by passive hemagglutination, in that they reacted with only one of the immunoglobulins of the panel used for their detection. A decrease of the overall IgE levels was observed in 62% of the subjects for a prolonged period of time following gamma-globulin administration. This suggests a feedback regulation mechanism for the reagin production in man, as it has already been observed in animals. A high incidence of anti-immunoglobulin antibodies of various classes was observed in this study. However, only a small number (4/43) of adverse reactions appeared following gamma-globulin administration. For some of these subjects, the presence of specific IgE anti-immunoglobulin, detected by the inverse-RAST technique, suggests a possible role of such antibodies in some intolerance reactions to gamma-globulin administration.

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