An Application of Homogenous Semi-Markov Model for Assessing HIV/AIDS Progression to ART Patients in Namibia

Background: The progression of HIV infection to AIDS and then to death can be considered a stochastic process. Disease progression can be broken down into a finite number of intermediate states, based on CD4 counts. The five states of the Markov process of HIV/AIDS progression are commonly defined as: S1: CD4 count > 500 cells/microliter; S2: 350 < CD4 count ≤ 500 cells/microliter; S3: 200 < CD4 count ≤ 350 cells/microliter; S4: CD4 count ≤ 200 cells/microliter; and D: Death.

Objectives: The objective of this study was to model the progression of HIV/AIDS disease of patients under ART follow-up in Namibia using homogenous semi-Markov processes, using the data obtained from Ministry of Health and Social Services.

Methods: A retrospective study design was used to obtain data on 2422 patients who were observed 11028 times. The semi-Markov model was employed to estimate the transition probabilities and transition intensity rate. Time Homogeneous Semi-Markov model was fitted to assess effectiveness of ART by comparing the forward transition and reverse transitions.

Results: As expected the probabilities of transiting from good states to worse states increased with time (from state 1 to state 3 and 4 after 6 months is 0.023 and 0.004, after 12 months is 0.059 and 0.010 respectively). As time increase the probabilities of remaining in the same state is decreasing (probabilities of remaining in state 1 after 6, 12 and 18 months is 0.804, 0.698 and 0.633). As expected the intensity indicates that the rate of transiting from good states to worst states is decreasing (the intensity of transiting from state 1 to 3 and 4 is p<0.001).

The strongest predictor of transition from state 1 to 2 is TDF/3TC/EFV, which has a hazard ratio of 1.338 (with p value of 0.002). Patients who were prescribed TDF/3TC/EFV, are over 1.338 times more likely to transit from state 1 to state 2 than patients who did not receive TDF/3TC/EFV. A hazard ratio of 0.678 for the predictor variable female shows that female were less likely to transit from state 2 to 3 than their male counterparts. The hazard ratios of females from a bad state to a better state are more than 1, which is an indication that females are less likely to respond to treatment compared to males.

Conclusions: HIV can progress to AIDS without delay if there is no intervention. Early ART initiation is crucial to reduce the probabilities of transiting from good states to worse states.