USE OF IMMUNOLOGICAL MARKERS AND CONTINUOUS-TIME MARKOV-MODELS TO ESTIMATE PROGRESSION OF HIV-INFECTION IN HOMOSEXUAL MEN

Objectives: We used continuous-time Markov models based on CD4 cell co unts and anti-CD3 reactivity (i.e., measure for T-cell quality) to stu dy the progression of HIV infection in a cohort study of homosexual me n in Amsterdam. We also compared the effectiveness of anti-CD3 reactiv ity as a marker for disease progression with that of CD4 cell counts. Methods: We used data from 467 men (6905 visits) with visits at 3-mont h intervals between October 1984 and March 1993. To account for measur ement error and short time-scale variability, the immunological stage at each visit was determined using a kernel smoother on log-transforme d data from each individual. The Markov model had six marker-defined s tages and a seventh stage for clinical AIDS. The initial stage-occupat ion probabilities for seroconverters were used to estimate the incubat ion time from infection to AIDS. Confidence intervals were calculated using the bootstrap method to account for the effect of smoothing on t he variability of our estimates. Results: The CD4 staging scheme estim ated the median time from seroconversion to AIDS at 8.3 years [95% con fidence interval (CI), 8.1-8.6], and a similar estimate was obtained w ith the anti-CD3 staging model. The CD4 model predicts that 10.2% (95% CI, 9.9-13.1) will remain AIDS-free 15 years after seroconversion. Th e mean number of stages visited before AIDS is lower with the CD4 mode l (7.4; 95% CI, 7.2-7.7) than with the anti-CD3 model (11.3; 95% Cl, 1 0.8-12.0), implying that anti-CD3 predicts progression less well than CD4 cell count. Conclusions: CD4 lymphocyte counts and anti-CD3 reacti vity are each associated with an increased hazard for progression to A IDS. Therefore, men in different CD4-stages (anti-CD3 stages) follow d ifferent incubation period distributions to AIDS. However, anti-CD3 pr edicts progression less well than CD4 cell count. Staged time-continuo us Markov models are useful to study immunological markers for HIV dis ease progression.