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A simple non-parametric approach is developed to simultaneously estimate net incidence and morbidity time from specific AIDS illnesses in populations at high risk for death from these illnesses and other causes. The disease-death process has four-stages that can be recast as two sandwiching three-state multiple decrement processes. Non-parametric estimation of net incidence and morbidity time with error bounds are achieved from these sandwiching models through modification of methods from Aalen and Greenwood, and bootstrapping. An application to immunosuppressed HIV-1 infected homosexual men reveals that cytomegalovirus disease, Kaposi's sarcoma and Pneumocystis pneumonia are likely to occur and cause significant morbidity time.

Objective: To estimate the incidence and prevalence of cytomegalovirus retinitis (CMV-R) in late-stage human immunodeficiency virus type 1 disease., Design: Cohort study., Setting: The Multicenter AIDS Cohort Study, an ongoing 10-year study of human immunodeficiency virus type 1-infected homosexual men with semiannual visits and CD4+ cell testing., Study Participants: Three hundred sixty-seven human immunodeficiency virus type 1-infected men from the Multicenter AIDS Cohort Study who were receiving zidovudine and Pneumocystis carinii prophylaxis and who had CD4+ cell counts fall below 0.10 x 10(9)/L (100/microL)., Main Outcome Measures: Kaplan-Meier-type estimates for various longitudinal quantifications of incidence and prevalence of CMV-R were obtained., Results: Among these 367 individuals, cytomegalovirus disease developed in 103, of whom 73 (71%) had ocular complications. At 4 years after the first CD4 cell count ( < 0.10 x 10(9)/L), the probability for these subjects to have (1) remained living without CMV-R was 11%, (2) died without experiencing CMV-R was 66%, (3) experienced CMV-R and be living was 6%, and (4) experienced CMV-R and died was 18%. During these 4 years, there was a 25% chance for the development of CMV-R and, on average, 0.211 person-years of CMV-R morbidity. Among those subjects in whom CMV-R developed, about 19% did have CMV-R before a CD4+ cell count of less than 0.05 x 10(9)/L ( < 50/microL) was observed, and 81% had CMV-R after the CD4+ cell count reached this threshold., Conclusion: These estimates may be relevant to current clinical practice and help in allocating resources and planning for treatment and prophylaxis against cytomegalovirus disease.

Projection disease incidence, prevalence, and net morbidity is often needed when individuals are likely to die, either disease free or after the disease has developed. Examples of this include remission of cancer or heart disease in elderly people who can die from these or other causes and occurrence of a particular acquired immune deficiency syndrome illness in human immunodeficiency virus type 1 (HIV-1) disease. Death is not an ancillary event but, rather, indicates either and end to disease morbidity or an end to risk to ever develop the disease. Thus, time to disease survival analyses that censor disease-free individuals at death can produce misleading results. The paper describes several useful quantifications of disease and death for this setting. A paradigm that utilizes Kaplan-Meier functions to estimate these quantities is introduced. The approach anchors on a four-stage disease/death model: stage A, living without disease; stage B, dead without ever developing disease; stage C, developed the disease and living; and stage D, dead after developing the disease. An application is made to projecting cytomegalovirus disease in a cohort of HIV-1-infected users of zidovudine and Pneumocystis prophylaxis from the Multicenter AIDS Cohort Study (MACS) during 1989-1993. At 3 years after a CD4+ count below 100/microliters, a man had an 18.7%, 46.3%, 5.3% or 29.9% chance, respectively, to be in stage A, B, C, or D. This man, on average, had 0.28 years of cytomegalovirus morbidity during these 3 years.