REPLACING TIME SINCE HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION BY MARKERVALUES IN PREDICTING RESIDUAL TIME TO ACQUIRED-IMMUNODEFICIENCY-SYNDROME DIAGNOSIS

It is widely assumed that the time since human immunodeficiency virus (HIV) infection is an important indicator of HIV disease stage, yet fo r most infected individuals the date of infection is unknown. We consi der whether marker values, such as CD4 lymphocyte number or percent an d levels of serum beta(2) microglobulin or serum neopterin, render tim e since infection unimportant for predicting the residual time to acqu ired immunodeficiency syndrome (AIDS) diagnosis. The Multicenter AIDS Cohort Study (MACS) contains a subsample of homosexual men whose date of HIV seroconversion is known within +/-6 months and who provide data for this analysis. From this subsample, we extract two overlapping da ta subsets. The first subset consists of 370 persons whose 3,723 study visits include complete data on the cellular markers CD4 lymphocyte n umber and percent for a period of 9 years. The second consists of 272 persons whose 1,593 visits include complete information on cellular ma rkers and on the serological markers beta(2)-microglobulin and neopter in for a period of 5 1/2 years. We model the residual time to AIDS dia gnosis with a regression model, in which cellular and serologic marker s are the explanatory covariates (independent variables) and the resid ual time to AIDS is the responses variable (dependent variable). A rob ust estimate of the variance-covariance matrix corrects for the depend ence of repeated measurements in the same individual. In the case of C D4 number and percent, the results indicate that time since infection is of none or at most little importance if the marker value is known, suggesting that time since infection can be adequately replaced by the combination of marker values. However, the serological markers alone do not eliminate the importance of the time since infection.