Modeling the trajectory of CD4 cell count and its effect on the risk of AIDS progression and TB infection among HIV-infected patients using a joint model of competing risks and longitudinal ordinal data

Background: This study was conducted to better understand the influence of prognostic factors and the trend of CD4 cell count on the risk of progression to acquired immunodeficiency syndrome (AIDS) and tuberculosis (TB) infection among patients with human immunodeficiency virus (HIV) in a developing country.  Methods: The information of 1530 HIV-infected patients admitted in Behavioral Diseases Counseling Centers, Tehran, Iran, (2004-2014) was analyzed in this study. A joint model of ordinal longitudinal outcome and competing events is used to model longitudinal measurements of CD4 cell count and the risk of TB-infection and AIDS-progression among HIV patients, simultaneously.  Results: The results revealed that the trend of CD4 cell count had a significant association with the risk of TB-infection and AIDS-progression (p<0.001). Higher ages (p<0.001), the history of being in prison (p=0.013), receiving antiretroviral therapy (ART) (p<0.001) and isoniazid preventive therapy (IPT) (p<0.001) were associated with the positive trend of CD4 cell count. Higher ages were also associated with higher risks of TB (p<0.001) and AIDS-progression (p<0.001). Furthermore, ART (p=.0009) and IPT (p<0.001) were associated with a lower risk of TB-infection. In addition, ART (p<0.001) was associated with a lower risk of AIDS-progression. Moreover, individuals being imprisoned (p=0.001) and abusing alcohol (p=0.012) were more likely to have TB-co-infection.  Conclusions: The used joint model provided a flexible framework for simultaneous studying of the effects of covariates on the level of CD4 cell count and the risk of progression to TB and AIDS. This model also assessed the effect of CD4 trajectory on the hazards of competing events.