Search

Background: Overproduction of beta-chemokines and genetic variations in chemokine receptors have been correlated with protection against infection by HIV-1 or slow progression to AIDS in infected individuals., Study Design and Methods: The protective role of chemokines and their receptors was evaluated in a group of seven uninfected (seronegative) hemophiliacs transfused with hemoderivatives presumably contaminated with HIV-1. This group was compared to a group of seven infected (seropositive) hemophiliacs and a group of healthy donors (controls). The CD4+ cell count, intracellular cytokine levels, beta-chemokine levels in plasma, beta-chemokine production by PBMNCs, and expression of chemokine receptors CCR5 and CXCR4 in CD4+ cells were evaluated. The occurrence of protective genotypes in CCR5, CCR2b, and SDF-1 (stromal cell-derived factor 1) genes and susceptibility to infection by HIV-1 were also studied., Results: Significant differences in the production and plasma levels of beta-chemokines among the three groups were not detected. Lower IL-2 and IFN-gamma production was observed in the uninfected exposed hemophiliacs than in the controls. Genetic analysis of CCR5, CCR2b, and SDF-1 showed several polymorphisms associated with resistance in some HIV-exposed uninfected hemophiliacs. However, these genetic features cannot explain the protection of all exposed hemophiliacs. In fact, only one patient, carrying two copies of CCR5 from which 32 bp was deleted, showed low CCR5 expression and low susceptibility to infection by a CCR5-using HIV-1 strain. In contrast, PBMNCs from all other individuals supported infection in vitro by both CCR5- and CXCR4-using HIV-1 strains., Conclusion: It is not possible to assign to beta-chemo-kines and polymorphisms in chemokine receptors a central role in preventing HIV-1 infection. Natural protection against HIV-1 infection is likely to be due to a multiplicity of factors.

The aim of the present study was to assess the interlaboratory reproducibility of the FACSCount system for the enumeration of peripheral blood (PB) CD4(+) T-cells. In each of the seven participating centers, both previously stained and unstained PB samples (n = 49) were received and either analyzed or stained and then analyzed. Interlaboratory reproducibility was checked in two different groups of centers (n = 3 and n = 4) where the study was performed in parallel. In addition, both the intralaboratory precision and accuracy of this system were analyzed in comparison with results obtained with conventional flow cytometry. Accordingly, upon comparing both methods, a high degree of correlation was observed in the total number of CD3(+) T-cells (coefficient of correlation of 0.9750 +/- 0.0184, slope of the best linear fit: 0. 9214 +/- 0.0311, y-intercept of 12 +/- 47) as well as in the number of CD3(+)/CD4(+) (coefficient of correlation of 0.9794 +/- 0.1457, slope of the best linear fit: 0.9463 +/- 0.0753, y-intercept of -11 +/- 36) and CD3(+)/CD8(+) (coefficient of correlation of 0.9728 +/- 0.0192, slope of the best linear fit: 0.9682 +/- 0.0735, y-intercept of 7 +/- 95) major subsets. In addition, low coefficients of variation (CV) were obtained for replicates, indicating the method's high degree of accuracy. The present study shows that with respect to the interlaboratory reproducibility reported for most techniques used for the enumeration of PB CD4(+) T-cells, the FACSCount system results in data with much lower coefficients of variance (CVs) (mean CV of less than 10%). Upon measuring the impact on results of different variables associated with either sample preparation or data acquisition and analysis, our study clearly shows that data acquisition and analysis does not influence the results by increasing variability since the coefficients of variation obtained for samples prepared in the same laboratory under the same conditions and read in different laboratories with different instruments were identical to those obtained for the replicates of the same samples read in each individual center. In contrast, interlaboratory variability, although low, significantly increased when sample preparation was carried out in different laboratories, suggesting that pipetting still represents the major source of variability in the FACSCount system., (Copyright 1999 Wiley-Liss, Inc.)

The CCR5 chemokine receptor is required by non-syncytium HIV-1 strains to infect target cells. A 32 base pair deletion (delta32) in the CCR5 gene causes a structural CCR5 modification that does not permit HIV-1 entry into cells. The rate of the CCR5 delta32 was investigated in 137 children born from HIV-infected mothers. Overall, five (10.6%) of 47 HIV-infected infants showed the defect in heterozygosis vs. eight (8.9%) of 90 uninfected children. No CCR5 delta32 homozygotes were found. Interestingly, among infected children, five (21.7%) of 23 showing a slow disease progression were heterozygous for the CCR5 delta32, meanwhile none of the 24 infants with rapid disease course had the deletion (P = 0.022). In conclusion, the CCR5 delta32 defect does not protect against vertical HIV-1 transmission, but is associated with a delayed disease progression in HIV-infected children.

Transmission of HIV-1 from an infected mother to her child occurs in around 20% of cases. Although maternal, immunological, and virological factors have been implicated in transmission, clear association is not yet well defined. For this reason, we have conducted a study to determine the relative contribution of the above-mentioned factors with special emphasis on quantitative viral load. We studied 67 HIV-1-infected mothers during pregnancy and labor and their 69 newborns (two sets of twins) from two university hospitals in Barcelona. Plasma and cell samples were collected at delivery between January 1992 and May 1994, and HIV-1 RNA and p24 in plasma, CD4 cell counts, and tissue culture infectious doses (TCID) were measured. Diagnosis of infection in children was based on persistence of anti-HIV-1 antibodies at 18 months of age, a positive HIV-1 culture or polymerase chain reaction in two separate samples, or presence of signs or symptoms of AIDS before 18 months of age. Results showed a very high relationship between > 10(5)/ml viral RNA copies (odds ratio [OR] 22, 95% confidence interval [CI] 4.4-119.2, p < 0.00001), > 0.5 TCID (OR 17, 95% CI 2.1-139.7, p = 0.001), CDC B + C (OR 3.5, 95% CI 0.98-12.5, p = 0.055), < 400 CD4 cells (OR 4.1; 95% CL 1.1-15.4, p = 0.01) and transmission of HIV-1. In this study, a strong association between mother-to-child transmission of HIV-1 and a high maternal viral RNA load in plasma at delivery is demonstrated. Viral load, which is related to clinical and immunological status in the mother, is the main contributing factor for HIV-1 vertical transmission, and these findings may have global and even individual therapeutic implications.

Background: To evaluate the use of quantitative and functional immunologic parameters as prognostic markers of infection by the human immunodeficiency virus (HIV)., Methods: The number of CD4 and CD8 lymphocytes, the CD4/CD8 ratio, the percentage of interleukin 2 (IL-2) receptors, the response to phytohemaglutinin (PHA) and the production of interferon tau (IFN-tau), were analyzed in 85 patients with HIV infection: 14 with acquired immunodeficiency syndrome (AIDS) (stage IV), 16 with persistent generalized adenopathies (stage III), and 55 asymptomatic patients (stage II). Similarly, a control group of 35 blood donors with negative HIV serology was studied., Results: Over a period of 30 months, 17 patients (5 of stage III and 12 of stage II) evolved to stage IV. In a multivariate analysis the decrease in the number of CD4 lymphocytes in stage II and the decrease in the production of IFN-tau in stage II and III were the parameters associated with progression to stage IV., Conclusions: The decrease in the production of interferon tau in patients with infection by the human immunodeficiency virus in stage II and III as well as the decrease in the number of CD4 lymphocytes in stage II are prognostic factors associated with the evolution to stage IV of the infection.