To determine whether initial CD4 cell counts after human immunodeficiency virus (HIV) seroconversion have decreased over calendar time among participants in the Italian Seroconversion Study, HIV ...seroconverters who between 1985 and 1992 had a documented negative serology followed by a positive serology within 12 months and a first CD4 cell measurement within 24 months of seroconversion (defined as midpoint of negative and positive HIV tests) were cross-tabulated by year of seroconversion. Linear regression methods were used to examine temporal trends in initial CD4 level after adjustment for age, lag time of seroconversion, lag time of CD4 cell measurement, risk group, and clinical center. Between 1985 and 1992, the overall median initial CD4 cell level after seroconversion was 660 μl with a median lag time of 212 days and 137 days for seroconversion and first CD4 cell measurement, respectively. In univariate and multivariate models, the CD4 cell count increases of 4.3 and 4.2 cells μl/year, respectively, were not statistically significant. These data do not identify a trend of lower CD4 counts following HIV seroconversion in Italy and suggest indirectly that HIV has probably not become more virulent between 1985 and 1992.
The data of two cohort studies of HIV-infected individuals
were used to examine whether the
rate of CD4 decline is a determinant of HIV progression, independent of
the most recent CD4
count. Time ...from seroconversion to clinical AIDS was the main outcome measure.
Rates of
CD4 decline were estimated using the ordinary least squares regression
method. AIDS
incidences were compared in individuals who had previously experienced
either a steeper or a
less steep rate of CD4 decline. Cox proportional hazards model including
a time-dependent
covariate for the rate of CD4 decline was performed. The rate of prior
CD4 decline was
significantly associated with the risk of developing AIDS independently
from the most recent
CD4 count, with a 2% increase in hazard of AIDS (P<·01)
for a difference of 10 cells/mm3 in the estimated yearly
drop
in CD4 count. This finding gives scientific credit to the belief that
individuals with a prior steeper CD4 decline consistently have a higher
subsequent risk of
developing AIDS than those with a less steep prior decline.
To evaluate if different levels of human herpesvirus 6 (HHV-6) antibodies can predict HIV disease progression.
Longitudinal study of individuals with a documented date of HIV seroconversion.
Clinical ...centers located throughout Italy.
Individuals who serconverted for HIV between 1983 and 1995 in Italy.
Sera were tested for IgG antibodies to HHV-6 using a commercial enzyme immunoassay. A serum sample with an optical density (OD) > or =242 (i.e. the mean value of 10 negative controls +4x standard deviation) was considered as HHV-6 positive; the progression of HIV disease was evaluated estimating the relative hazards (RH) of AIDS (by Cox models) for individuals with higher levels vs. lower levels of HHV-6 antibodies or considering levels of antibodies based on 10% increase of the distribution (deciles). Rates of CD4 decline fitting linear regression were also estimated.
A total of 381 persons were followed for a median time of 4 years (range: 0.15-9 years) following the date of collection of the serum sample. The median OD value of HHV-6 antibodies was 306, with an interquartile range of 241-440 and a range of 48-2330. A slight inverse correlation was found between HHV-6 antibody levels and age of the individual at the time of serum collection (Spearman rank correlation coefficient, -0.16; p = 0.0013). No association was found between HHV-6 and CD4 level or between HHV-6 and CD8 level at the date of serum collection. The unadjusted RH of progression to AIDS was 0.63 (95% CI: 0.42-0.96) for HHV-6 positive individuals vs. HHV-6 negative; when adjusting for possible confounders (CD4, age, pre-AIDS HIV-related pathologies at the date of sera collection, and previous anti-herpes treatment), the RH of AIDS increased to 0.80 (95% CI: 0.51-1.23). No particular association with HIV disease progression was found when using the deciles of the distribution of HHV-6 antibodies. The median CD4 cell loss was 5.0x10(6) cells/l per month among HHV-6 positive individuals and 5.7x10(6) cells/l per month among the others.
The presence of high levels of HHV-6 antibodies does not seem to predict the clinical or immunologic progression of HIV disease.
We adapt the aliasing constraints approach for designing a flexible typing of evolving objects. Types are singleton types (addresses of objects, as a matter of fact) whose relevance is mainly due to ...the sort of safety property they guarantee. In particular we provide a type system for an imperative object based calculus with delegation and which supports method and delegate overriding, addition, and removal.
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