The main results showed there were 79% and 68% decrease of AIDS-related mortality risk in immediate ART and delayed ART compared with late ART, whether in patients of high and low CD4+ cell counts. Additional risk factors for mortality in this study were male, older age, farmer, AIDS stage at diagnosis, infection by blood transmission, low educational level, and single. Our results confirm WHO’s guidelines on the use of antiretroviral drugs for treating and preventing HIV infection.
The mechanism of ART decreasing the mortality risk was primarily through viral suppression and improved immunological recovery[16]. Earlier initiation strategy of ART based on CD4+ cell counts has been reported to prevent HIV transmission and reduce the rate of clinical events[17]. CD4+ cell counts level is the most important laboratory indicator of immune function. When CD4+ cell counts declines below a certain level, HIV infected individuals are at a risk of immune deficiency and more susceptible to infection, resulting in advancement of AIDS or death[18]. In present study, after controlling for CD4+ cell counts and other confounds factors, risk of AIDS-related mortality decreased with earlier of ART initiation time. We also found that patients with high baseline CD4+ cell counts who initiated ART after a year had a 9% higher risk of AIDS-related death than those with lower baseline CD4+ cell counts who initiated ART after 90 days but within 1 year. Patients with high CD4+ levels at baseline who missed treatment opportunity would have a worse prognosis than those with lower CD4+ levels at baseline[19, 20]. Arguments to delay ART initiation based on the use of a CD4+ cell count threshold include concerns about drug resistance, side effects, and resource allocation[21–26]. However, previous studies have concluded that the public health benefits of immediate ART initiation more than the risks. For example, Zhao et al. discovered immediate ART when CD4+ counts > 500 cells/µL could reduce the mortality within a year[27]. Our results emphasized the importance of immediate ART initiation for long-term survival among FPD with high and low CD4+ cell counts. Therefore, early screening and immediate treatment after diagnosis should to be advocated, such as all patients could voluntary test, counsel, and entry into Chinese National Free Antiretroviral Treatment Program[28].
Illegal commercial plasma and blood collection activities were very common in rural central China before the national blood donation law was enacted[29]. 76.0% of HIV/AIDS patients among FPD in the present study were infected through blood transmission. Patients infected via blood transmission had higher plasma HIV load and lower CD4+ cell counts than patients infected by sexual transmission, resulting in faster progression of AIDS or earlier death[30]. Mortality was higher among the older males may be attributed to late diagnosis, comorbidities, and poor immunological response to ART[31, 32]. Educational level was negatively associated with AIDS-related mortality, which is the result of the educated individuals were more likely to adopt protective measures than the others[33, 34]. Lower AIDS-related mortality risk was observed among the married, which may be explained having fewer sexual partners and being sexually safe[35].
Discrimination is an important characteristic in the evaluation of model performance[36]. In the presence of competing events, discrimination is typically characterized using the time-dependent ROC curve[37, 38]. In this study, the AUC(t) values of each year from multivariate competing risk were above 0.80 in the first 11 years. After 12 years of follow-up, the AUC value decreased and the 95% CI expanded. The convincing reason is that the new reported mortality after 12 years was very low (AIDS-related death at 12, 13, 14, and 15 years after diagnosis was 54, 8, 2, and 0, respectively). At this time, competitive risk model is inapplicable to evaluate the prognostic factors of AIDS-related mortality.
The present study has several strengths. Firstly, our study includes large sample size and long follow-up time. Secondly, it explored association between time from HIV diagnosis to ART initiation and AIDS-related mortality among HIV/AIDS patients among high or low CD4+ cell counts levels. Finally, it was the first study to evaluate the predictors of AIDS-related mortality based on competing risk model and time-dependent ROC. Inevitably, this study has some limitations. Firstly, we don’t consider dynamic changes of CD4+ cell counts during follow-up may influence the survival in HIV/AIDS for higher proportion of missing value in CD4+ cell counts. Secondly, the compliance of ART, which may influence HIV/AIDS prognosis, was not considered in the present analysis because of unavailability of data. In future studies, details on the dynamic changes of CD4+ cell counts and ART compliance should be considered to explore their influence on AIDS-related mortality.