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Abstract

HIV/AIDS progression is inherently a multi-state stochastic process in which transitions among immunological states evolve over time and are influenced by therapeutic interventions. Standard homogeneous Markov models cannot adequately capture this temporal heterogeneity, necessitating more flexible stochastic frameworks. This study develops and evaluates a multi-state non-homogeneous semi-Markov model (MNHSMM) for characterizing HIV progression across six clinically defined immunological states and estimating state-specific sojourn-time distributions and transition probabilities as functions of calendar time and treatment status. Longitudinal data from 500 HIV-positive adults followed for a median of 84 months were analyzed. The proposed six-state MNHSMM incorporated Weibull-distributed sojourn times and time-varying transition kernels parameterized using B-spline functions, with parameters estimated through maximum likelihood estimation. Model performance was compared with that of homogeneous Markov and homogeneous semi-Markov models using the Akaike information criterion (AIC), Bayesian information criterion (BIC), and likelihood-ratio tests. The MNHSMM achieved the lowest AIC (3281.4) and BIC (3402.6) and significantly outperformed the homogeneous semi-Markov model, χ²(16) = 174.2, p < .001. The mean sojourn time in the asymptomatic state was 28.4 months (95% CI [25.1, 31.7]). Patients receiving antiretroviral therapy exhibited significantly longer sojourn times across all nonabsorbing states and a 37% lower probability of transitioning to death within five years. These findings establish the MNHSMM as a statistically superior and clinically informative framework for modeling HIV progression. Its temporal flexibility can improve long-term survival prediction, support the identification of optimal antiretroviral therapy intervention windows, and inform healthcare planning in sub-Saharan Africa and beyond.

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Article Details

How to Cite
Kinafa, A. U., Kwami, A., & Alhajiyel, M. H. (2026). A Multi-State Non-Homogeneous Semi-Markov Model with Application to HIV/AIDS Disease Progression. Mikailalsys Journal of Advanced Engineering International, 3(3), 296-308. https://doi.org/10.58578/mjaei.v3i3.9909

References

Barbu, V. S., & Limnios, N. (2008). Semi-Markov chains and hidden semi-Markov models: Toward applications. Springer. https://doi.org/10.1007/978-0-387-73173-5

Davidov, O., & Zelen, M. (2000). Designing cancer prevention trials: A stochastic model approach. Statistics in Medicine, 19(15), 1983–1995. https://doi.org/10.1002/1097-0258(20000815)19:15%3C1983::AID-SIM534%3E3.0.CO;2-E

de Boor, C. (2001). A practical guide to splines (Rev. ed.). Springer. https://doi.org/10.1007/978-1-4612-6333-3

Efron, B., & Tibshirani, R. J. (1993). An introduction to the bootstrap. Chapman & Hall. https://doi.org/10.1007/978-1-4899-4541-9

Foucher, Y., Mathieu, E., Saint-Pierre, P., Durand, J. F., & Daurès, J. P. (2005). A semi-Markov model based on a generalised Weibull distribution with an illustration for HIV disease. Biometrical Journal, 47(6), 825–833. https://doi.org/10.1002/bimj.200410149

Gentleman, R. C., Lawless, J. F., Lindsey, J. C., & Yan, P. (1994). Multi-state Markov models for analysing incomplete disease history data with illustrations for HIV disease. Statistics in Medicine, 13(8), 805–821. https://doi.org/10.1002/sim.4780130803

Hontelez, J. A. C., de Vlas, S. J., Baltussen, R., Newell, M.-L., Bakker, R., Tanser, F., Lurie, M. N., & Bärnighausen, T. (2012). The impact of antiretroviral treatment on the age composition of the HIV epidemic in sub-Saharan Africa. AIDS, 26(Suppl. 1), S19–S30. https://doi.org/10.1097/QAD.0b013e3283558526

Howard, R. A. (1971). Dynamic probabilistic systems: Vol. 2. Semi-Markov and decision processes. Wiley.

Janssen, J., & Manca, R. (2006). Applied semi-Markov processes. Springer. https://doi.org/10.1007/0-387-29548-8

Kahn, J. G., Garnett, G. P., Leung, B., & Sacks, H. S. (1992). The costs and benefits of antiretroviral therapy in AIDS: A model-based analysis. AIDS, 6(2), 145–151. https://doi.org/10.1097/00002030-199202000-00004

Limnios, N., & Oprişan, G. (2001). Semi-Markov processes and reliability. Birkhäuser. https://doi.org/10.1007/978-1-4612-0161-8

Longini, I. M., Jr., Clark, W. S., Byers, R. H., Ward, J. W., Darrow, W. W., Lemp, G. F., & Hethcote, H. W. (1989). Statistical analysis of the stages of HIV infection using a Markov model. Statistics in Medicine, 8(7), 831–843. https://doi.org/10.1002/sim.4780080708

Meira-Machado, L., de Uña-Álvarez, J., Cadarso-Suárez, C., & Andersen, P. K. (2009). Multi-state models for the analysis of time-to-event data. Statistical Methods in Medical Research, 18(2), 195–222. https://doi.org/10.1177/0962280208092301

Mellors, J. W., Muñoz, A., Giorgi, J. V., Margolick, J. B., Tassoni, C. J., Gupta, P., Kingsley, L. A., Todd, J. A., Saah, A. J., Detels, R., Phair, J. P., & Rinaldo, C. R., Jr. (1997). Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Annals of Internal Medicine, 126(12), 946–954. https://doi.org/10.7326/0003-4819-126-12-199706150-00003

Nakagawa, F., Lodwick, R. K., Smith, C. J., Smith, R., Cambiano, V., Lundgren, J. D., Delpech, V., & Phillips, A. N. (2012). Projected life expectancy of people with HIV according to timing of diagnosis. AIDS, 26(3), 335–343. https://doi.org/10.1097/QAD.0b013e32834dcec9

Norris, J. R. (1997). Markov chains. Cambridge University Press. https://doi.org/10.1017/CBO9780511810633

Pérez-Ocón, R., Ruiz-Castro, J. E., & Gámiz-Pérez, M. L. (2001). Non-homogeneous Markov models in the analysis of survival after breast cancer. Journal of the Royal Statistical Society: Series C (Applied Statistics), 50(1), 111–124. https://doi.org/10.1111/1467-9876.00223

Stover, J., Glaubius, R., Mofenson, L., Dugdale, C. M., Davies, M.-A., Patten, G., & Yiannoutsos, C. (2019). Updates to the Spectrum/AIM model for estimating key HIV indicators at national and subnational levels. AIDS, 33(Suppl. 3), S227–S234. https://doi.org/10.1097/QAD.0000000000002357

Titman, A. C., & Sharples, L. D. (2008). A general goodness-of-fit test for Markov and hidden Markov models. Statistics in Medicine, 27(12), 2177–2195. https://doi.org/10.1002/sim.3033

Titman, A. C., & Sharples, L. D. (2010). Semi-Markov models with phase-type sojourn distributions. Biometrics, 66(3), 742–752. https://doi.org/10.1111/j.1541-0420.2009.01339.x

Touloumi, G., Pantazis, N., Antoniou, A., Stirnadel, H. A., Walker, S. A., Porter, K., & CASCADE Collaboration. (2006). Highly active antiretroviral therapy interruption: Predictors and virological and immunological consequences. Journal of Acquired Immune Deficiency Syndromes, 42(5), 554–561. https://doi.org/10.1097/01.qai.0000230321.85911.db

UNAIDS. (2023). Global HIV & AIDS statistics—Fact sheet. https://www.unaids.org/en/resources/fact-sheet

Wood, S. N. (2017). Generalized additive models: An introduction with R (2nd ed.). Chapman & Hall/CRC. https://doi.org/10.1201/9781315370279

World Health Organization. (2016). Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection (2nd ed.). https://www.who.int/publications/i/item/9789241549684