title: On the inclusion of prevalent cases in HIV/AIDS natural history studies through a marker-based estimate of time since seroconversion.
abstract: In most cohort studies of HIV infection and AIDS, seroprevalent cases provide a substantial amount of information. Inclusion of these people in natural history studies requires a fairly unbiased method to estimate their seroconversion distribution. When a cohort-based estimate is not feasible, an alternative is to estimate individual seroconversion distributions, based on marker values at entry. In this paper, a non-parametric marker-based estimation method is developed. The method is applied to data from the Amsterdam cohort study on homosexual men. For seroprevalent cases who entered the study between October 1984 and April 1985, individual seroconversion distributions are estimated based on their first measured CD4 count. In subsequent survival analyses, dates of seroconversion are estimated via conditional mean imputation. Inclusion of these seroprevalent cases greatly improves the quality of the data. Age at seroconversion is a significant cofactor for disease progression, a result not found when analysis is restricted to those who seroconvert. To incorporate the uncertainty in the imputed date of seroconversion, a bootstrap procedure is developed for the computation of p-values and confidence intervals. In our analyses, standard procedures, which ignore the uncertainty in the imputed date of seroconversion, perform almost as well.
authors.affiliation: Municipal Health Service, Division of Public Health and Environment, Nieuwe Achtergracht 100, 1018 WT Amsterdam, The Netherlands. rgeskus@gggd.amsterdam.nl
authors.forename: R B
authors.initials: RB
authors.lastname: Geskus
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000453:epidemiology* / Q000209:etiology* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D016001:Confidence Intervals; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D006679:HIV Seropositivity / Q000097:blood / Q000150:complications* / Q000453:epidemiology* / Q000276:immunology; D015528:HIV Seroprevalence; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D015415:Biomarkers