The specific aims of this study were: (1) to model the natural history of anal neoplasia in HIV-infected patients by estimating cytology-based transition probabilities and transition rates (per person-year) under a 3-state model of anal cancer pathogenesis, adjusting for cytology misclassification; and (2) to estimate the effects of selected time-varying covariates on transition probabilities: CD4+ lymphocyte category, HIV plasma viral load suppression, antiretroviral therapy, smoking, and treatment of anal cancer precursors with infrared coagulation (IRC). The gene discussed is CD4; the disease is anal carcinoma.