Prediction of survival and opportunistic infections in HIV infected patients: a comparison of imputation methods of incomplete CD4 counts

Abstract

In evaluating the risk of mortality or development of opportunistic infections in HIV-infected patients, the number of CD4 lymphocyte cells per cubic millimetre of blood is widely recognized as one of the best available predictors of such future events. However, its usefulness is limited by the incompleteness and variability of such CD4 measurements during follow-up. Because of these limitations, analysis of such data requires the missing measurements to be filled in or the patients without them to be excluded. We consider multiple imputation of CD4 values based partly on information from other health status measures such as haemoglobin, as well as on the event status of interest. These alternative health status measures are also considered as possible independent predictors of survival endpoints. Our work is motivated by a cohort of 1530 patients enrolled in two AIDS clinical trials. We compare our approach to other strategies such as basing evaluation of risk on baseline CD4, the last measured CD4 before an event, or a time-dependent covariate based on carrying the last CD4 value forward; we conclude with a strong recommendation for multiple imputation.