TRACKING OF MARKERS AND ONSET OF DISEASE AMONG HIV-1 SEROCONVERTERS

Repeated measurements on persons infected with HIV-1 indicate that inf ection has a dynamic impact on several markers of immune suppression a nd activation. The objectives of this report are: (a) to provide a sta tistical model for the correlation structure of serial measurements of immunological markers, and (b) to identify features of marker profile s associated with the timing of AIDS diagnoses. We analyse data obtain ed from 328 seroconverters participating in the Multicenter AIDS Cohor t Study on whom the date of HIV-1 seroconversion is known within +/- 4 .5 months. Immunological markers considered here are CD4 cell counts, serum beta2-microglobulin and serum neopterin. The statistical model f or HIV-related changes in markers consists of (1) a piecewise linear r egression model for the trajectories of markers over time and (2) a tw o-parameter autocorrelation function that generalizes Markovian and si mple random effects autocorrelation structures. Application of this mo del for marker measurements revealed a high degree of tracking, as the estimated autocorrelation function exhibited sub-exponential decay ov er time. Though current marker levels are most informative on future v alues, there is substantial information (memory) in previous measureme nts. A feature suggested by the analysis of groups formed according to the length of the AIDS-free period, is the sequential divergence of t he CD4 trajectories where steeper declines occurred with a two-year la g prior to AIDS onset. For AIDS cases diagnosed 3-5 and 5-7 years afte r seroconversion, the rates of decline compared with those free of AID S for at least 4 years were steeper by 95 and 46 per cent respectively at two years prior to AIDS.