Methods of competing risks flexible parametric modeling for estimation of the risk of the first disease among HIV...

Patients infected with the Human Immunodeficiency Virus (HIV) are susceptible to many diseases. In these patients, the occurrence of one disease alters the chance of contracting another. Under such circumstances, methods for competing risks are required. Recently, competing risks analyses in the scope of flexible parametric models have risen to address this requirement. These lesser-known analyses have considerable advantages over conventional methods.

Using data from Multi Centre AIDS Cohort Study (MACS), this paper reviews and applies methods of competing risks flexible parametric models to analyze the risk of the first disease (AIDS or non-AIDS) among HIV-infected patients. We compared two alternative subdistribution hazard flexible parametric models (SDH_FPM1 and SDH_FPM2) with the Fine & Gray model. To make a complete inference, we performed cause-specific hazard flexible parametric models for each event separately as well.

Both SDH_FPM1 and SDH_FPM2 provided consistent results regarding the magnitude of coefficients and risk estimations compared with estimations obtained from the Fine & Gray model, However, competing risks flexible parametric models provided more efficient and smoother estimations for the baseline risks of the first disease. We found that age at HIV diagnosis indirectly affected the risk of AIDS as the first event by increasing the number of patients who experience a non-AIDS disease prior to AIDS among > 40 years. Other significant covariates had direct effects on the risks of AIDS and non-AIDS.

The choice of an appropriate model depends on the research goals and computational challenges. The SDH_FPM1 models each event separately and requires calculating censoring weights which is time-consuming. In contrast, SDH_FPM2 models all events simultaneously and is more appropriate for large datasets, however, when the focus is on one particular event SDH_FPM1 is more preferable.