Is the Time from HIV Seroconversion a Determinant of the Risk of AIDS After Adjustment for Updated CD4 Cell Counts?

The major effect of the progressive immune suppression caused by HIV-1 is an increased risk of a number of opportunistic infections and rare tumor types which define the clinical spectrum of AIDS. It has been reported that time from infection (seroconversion) is a strong prognostic marker for the onset of AIDS. Other studies have suggested that individuals with similar CD4 cell counts have similar rates of progression independent of different times from seroconversion. The objective of this study was to investigate, using a very large set of pooled cohorts, whether there is a residual effect of time from infection on the risk of AIDS and to quantify this effect in terms of an increase in risk. The study also investigated this objective for each specific AIDS-defining illness.

Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) is a collaboration of investigators involved with 19 cohorts in Europe and Australia that began in 1997. All cohorts contain individuals for whom it was possible to estimate the time of HIV seroconversion. All analysis ended with data at December 31, 1995 in order to avoid confounding the findings with the effect of highly active antiretroviral therapy (HAART), which became widely prescribed after that date. Using pooled data from 19 seroconverter cohorts, the authors considered time to the first AIDS-defining event following the CD4 cell count below 500 cells/mm³, 350 cells/mm³, and 200 cells/mm³. All data were adjusted for age, gender, exposure category, and HIV test interval in Cox Models stratified by cohorts.

Of 3,825, 3,006 and 1,804 individuals reaching CD4 thresholds of 500, 350, and 200 respectively, 1,274, 1,192 and 985, respectively, developed AIDS. The authors found a significant effect of time from seroconversion on the risk of AIDS even after adjusting for updated CD4 counts. The risks after one year were 7 percent, 6 percent and 4 percent, respective to the three cohort groupings. The effect of time appeared to be nonlinear, with no increase in the risk of AIDS after 4 years from seroconversion.

The residual effect of time differed significantly according to type of AIDS-defining event initially diagnosed. Time from seroconversion to CD4 threshold was not associated with progression to Pneumocystis carinii pneumonia (PCP), herpes simplex virus infection (HSV) and deaths in persons without AIDS. Conversely, time from seroconversion was found to have a stronger association with progression to Kaposi Sarcoma (KS) and mycobacterial disease, not including tuberculosis.

Given the results of the study, the authors advised against the use of time in assessing an infected individual's risk of AIDS over and above a given CD4 cell count. "Such knowledge, however, is of more benefit when assessing a patient's risk of KS or mycobacterial disease, other than tuberculosis, rather than PCP or HSV infection," the authors said.

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