Research article Special Issues

Effect of drug resistance on an HIV epidemic in heterogeneous populations

  • Published: 07 April 2026
  • The emergence of drug resistance (DR) may impair the control of the human immunodeficiency virus (HIV) epidemic. We analyze the transmission and drug-resistance dynamics of HIV using a stochastic model in combination with Monte Carlo simulations, which considers population heterogeneity, set in terms of the set-point viral load (SPVL) distribution. In our modeling framework, once a SPVL is sampled, it determines the transmission rate and survival time for each new infected individual. On the other hand, DR emergence randomly occurs with a fixed probability in an individual receiving antiretroviral therapy (ART). In addition, we implicitly assume that the SPVL serves as a proxy for the replication pressure and resistance risk, as the DR fitness-cost proportionally reduces the SPVL in our model (an assumption motivated by modeling convenience instead of an actual biological mechanism present in the DR dynamics). Finally, we simplify the dynamics by assuming no ART regimen switching in cases of treatment failure (which we assumed to be only due to DR). Our results show that for a high treatment coverage, DR causes a higher stationary infection prevalence in populations with moderate-to-high mean viral loads. Moreover, DR could produce more infections for greater ART coverage, especially when treatment is administered early after contagion; however, an earlier initiation of ART allows for the possibility of epidemic extinction. Additionally, we evaluate the effect on the epidemic dynamics of other parameters, such as the probability of DR emergence and the relative fitness of the DR strain. Overall, our analysis contributes to the understanding of drug resistance evolution in situations where ART is inadequately managed.

    Citation: Roberto A. Saenz. Effect of drug resistance on an HIV epidemic in heterogeneous populations[J]. Mathematical Biosciences and Engineering, 2026, 23(5): 1356-1374. doi: 10.3934/mbe.2026050

    Related Papers:

  • The emergence of drug resistance (DR) may impair the control of the human immunodeficiency virus (HIV) epidemic. We analyze the transmission and drug-resistance dynamics of HIV using a stochastic model in combination with Monte Carlo simulations, which considers population heterogeneity, set in terms of the set-point viral load (SPVL) distribution. In our modeling framework, once a SPVL is sampled, it determines the transmission rate and survival time for each new infected individual. On the other hand, DR emergence randomly occurs with a fixed probability in an individual receiving antiretroviral therapy (ART). In addition, we implicitly assume that the SPVL serves as a proxy for the replication pressure and resistance risk, as the DR fitness-cost proportionally reduces the SPVL in our model (an assumption motivated by modeling convenience instead of an actual biological mechanism present in the DR dynamics). Finally, we simplify the dynamics by assuming no ART regimen switching in cases of treatment failure (which we assumed to be only due to DR). Our results show that for a high treatment coverage, DR causes a higher stationary infection prevalence in populations with moderate-to-high mean viral loads. Moreover, DR could produce more infections for greater ART coverage, especially when treatment is administered early after contagion; however, an earlier initiation of ART allows for the possibility of epidemic extinction. Additionally, we evaluate the effect on the epidemic dynamics of other parameters, such as the probability of DR emergence and the relative fitness of the DR strain. Overall, our analysis contributes to the understanding of drug resistance evolution in situations where ART is inadequately managed.



    加载中


    [1] Joint United Nations Programme on HIV/AIDS, Global HIV & AIDS Statistics—Fact Sheet, 2025. Available from: https://www.unaids.org/sites/default/files/2025-07/2025_Global_HIV_Factsheet_en.pdf.
    [2] Joint United Nations Programme on HIV/AIDS, World AIDS Day Report, 2011. Available from: http://www.unaids.org/en/resources/documents/2011/.
    [3] M. S. Cohen, Y. Q. Chen, M. McCauley, T. Gamble, M. C. Hosseinipour, N. Kumarasamy, et al., Prevention of HIV-1 infection with early antiretroviral therapy, N. Engl. J. Med., 365 (2011), 493–505. https://doi.org/10.1056/NEJMoa1105243 doi: 10.1056/NEJMoa1105243
    [4] World Health Organization, Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring: Recommendations for A Public Health Approach, 2021. Available from: https://www.who.int/publications/i/item/9789240031593.
    [5] A. H. Peruski, B. Wu, L. Linley, K. P. Delaney, E. A. DiNenno, A. S. Johnson, Time from HIV infection to diagnosis in the U.S., 2014–2018, Am. J. Prev. Med., 61 (2021), 636–643. https://doi.org/10.1016/j.amepre.2021.04.015 doi: 10.1016/j.amepre.2021.04.015
    [6] F. Clavel, A. J. Hance, HIV drug resistance, N. Engl. J. Med., 350 (2004), 1023–1035. https://doi.org/10.1056/NEJMra025195 doi: 10.1056/NEJMra025195
    [7] S. Margeridon-Thermet, R. W. Shafer, Comparison of the mechanisms of drug resistance among HIV, hepatitis B, and hepatitis C, Viruses, 2 (2010), 2696–2739. https://doi.org/10.3390/v2122696 doi: 10.3390/v2122696
    [8] D. R. Bangsberg, E. P. Acosta, R. Gupta, D. Guzman, E. D. Riley, P. R. Harrigan, et al., Adherence-resistance relationships for protease and non-nucleoside reverse transcriptase inhibitors explained by virological fitness, AIDS, 20 (2006), 223–231. https://doi.org/10.1097/01.aids.0000199825.34241.49 doi: 10.1097/01.aids.0000199825.34241.49
    [9] R. M. Kagan, J. D. Baxter, T Kim, E. M. Marlowe, HIV-1 drug resistance trends in the era of modern antiretrovirals: 2018–2024, in Open Forum Infectious Diseases, Oxford University Press, US, 12 (2025), 1–9. https://doi.org/10.1093/ofid/ofaf446
    [10] S. Hué, R. J. Gifford, D. Dunn, E. Fernhill, D. Pillay, Demonstration of sustained drug-resistant human immunodeficiency virus type 1 lineages circulating among treatment-naive individuals, J. Virol., 83 (2009), 2645–2654. https://doi.org/10.1128/JVI.01556-08 doi: 10.1128/JVI.01556-08
    [11] J. O. Wertheim, A. M. Oster, J. A. Johnson, W. M. Switzer, N. Saduvala, A. L. Hernandez, et al., Transmission fitness of drug-resistant HIV revealed in a surveillance system transmission network, Virus Evol., 3 (2017), 1–12. https://doi.org/10.1093/ve/vex008 doi: 10.1093/ve/vex008
    [12] R. F. Baggaley, G. P. Garnett, N. M. Ferguson, Modelling the impact of antiretroviral use in resource-poor settings, PLoS Med., 3 (2006), e124. https://doi.org/10.1371/journal.pmed.0030124 doi: 10.1371/journal.pmed.0030124
    [13] S. Blower, E. Bodine, J. Kahn, W. McFarland, The antiretroviral rollout and drug-resistant HIV in Africa: insights from empirical data and theoretical models, AIDS, 19 (2005), 1–14.
    [14] R. A. Saenz, S. Bonhoeffer, Nested model reveals potential amplification of an HIV epidemic due to drug resistance, Epidemics, 5 (2013), 34–43. https://doi.org/10.1016/j.epidem.2012.11.002 doi: 10.1016/j.epidem.2012.11.002
    [15] M. Shen, Y. Xiao, L. Rong, L. A. Meyers, S. E. Bellan, Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance, Proc. R. Soc. B, 284 (2017), 20170525. https://doi.org/10.1098/rspb.2017.0525 doi: 10.1098/rspb.2017.0525
    [16] V. Supervie, M. Barret, J. S. Kahn, G. Musuka, T. L. Moeti, L. Busang, et al., Modeling dynamic interactions between pre-exposure prophilaxis interventions and treatment programs: Predicting HIV transmission and resistance, Sci. Rep., 1 (2011), 185. https://doi.org/10.1038/srep00185 doi: 10.1038/srep00185
    [17] B. G. Wagner, S. Blower, Universal access to HIV treatment versus universal 'test and treat': Transmission, drug resistance and treatment costs, PLoS One, 7 (2012), e41212. https://doi.org/10.1371/journal.pone.0041212 doi: 10.1371/journal.pone.0041212
    [18] C. Fraser, T. D. Hollingsworth, R. Chapman, F. de Wolf, W. P. Hanage, Variation in HIV-1 set-point viral load: Epidemiological analysis and an evolutionary hypothesis, Proc. Natl. Acad. Sci., 104 (2007), 17441–17446. https://doi.org/10.1073/pnas.0708559104 doi: 10.1073/pnas.0708559104
    [19] When To Start Consortium, Timing of initiation of antiretroviral therapy in AIDS-free HIV-1- infected patients: A collaborative analysis of 18 HIV cohort studies, Lancet, 373 (2009), 1352–1363. https://doi.org/10.1016/S0140-6736(09)60612-7
    [20] J. M. Heffernan, L. M. Wahl, Monte Carlo estimates of natural variation in HIV infection, J. Theor. Biol., 236 (2005), 137–153. https://doi.org/10.1016/j.jtbi.2005.03.002 doi: 10.1016/j.jtbi.2005.03.002
    [21] L. J. S. Allen, A. M. Burgin, Comparison of deterministic and stochastic SIS and SIR models in discrete time, Math. Biosci., 163 (2000), 1–33. https://doi.org/10.1016/S0025-5564(99)00047-4 doi: 10.1016/S0025-5564(99)00047-4
    [22] T. D. Hollingsworth, R. M. Anderson, C. Fraser, HIV-1 transmission, by stage of infection, J. Infect. Dis., 198 (2008), 687–693. https://doi.org/10.1086/590501 doi: 10.1086/590501
    [23] The UK Collaborative HIV Cohort (CHIC) Study Steering Committee, HIV diagnosis at CD4 count above 500 cells/mm$^3$ and progression to below 350 cells/mm$^3$ without antiretroviral therapy, J. Acquir. Inmune Defic. Syndr., 46 (2007), 275–278. https://doi.org/10.1097/QAI.0b013e3181514441
    [24] J. Martinez-Picado, M. A. Martinez, HIV-1 reverse transcriptase inhibitor resistance mutations and fitness: A review from the clinic and ex vivo, Virus Res., 134 (2008), 104–123. https://doi.org/10.1016/j.virusres.2007.12.021 doi: 10.1016/j.virusres.2007.12.021
    [25] J. M. Kitayimbwa, J. Y. T. Mugisha, R. A. Saenz, Estimation of the HIV-1 backward mutation rate from transmitted drug-resistant strains, Theor. Popul. Biol., 112 (2016), 33–42. https://doi.org/10.1016/j.tpb.2016.08.001 doi: 10.1016/j.tpb.2016.08.001
    [26] J. M. Kitayimbwa, J. Y. T. Mugisha, R. A. Saenz, The role of backward mutations on the within-host dynamics of HIV-1, J. Math. Biol., 67 (2013), 1111–1139. https://doi.org/10.1007/s00285-012-0581-2 doi: 10.1007/s00285-012-0581-2
    [27] V. Jain, M. C. Sucupira, P. Bacchetti, W. Hartogensis, R. S. Diaz, E. G. Kallas, et al., Differential persistence of transmitted HIV-1 drug resistance mutation classes, J. Infect. Dis., 203 (2011), 1174–1181. https://doi.org/10.1093/infdis/jiq167 doi: 10.1093/infdis/jiq167
    [28] Panel on Antiretroviral Guidelines for Adults and Adolescents, Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, Department of Health and Human Services, 2025. Available from: https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv. Accessed: February, 2026.
    [29] S. O. Gbadamosi, M. J. Trepka, R. Dawit, R. Jebai, D. M. Sheehan, A systematic review and meta-analysis to estimate the time from HIV infection to diagnosis for people with HIV, AIDS Rev., 24 (2022), 32–40. https://doi.org/10.24875/AIDSRev.21000007 doi: 10.24875/AIDSRev.21000007
    [30] M. Lipsitch, T. Cohen, M. Murray, B. R. Levin, Antiviral resistance and the control of pandemic influenza, PLoS Med., 4 (2007), e15. https://doi.org/10.1371/journal.pmed.0040015 doi: 10.1371/journal.pmed.0040015
    [31] S. M. Moghadas, C. S. Bowman, G. Rost, J. Wu, Population-wide emergence of antiviral resistance during pandemic influenza, PLoS One, 3 (2008), e1839. https://doi.org/10.1371/journal.pone.0001839 doi: 10.1371/journal.pone.0001839
  • Reader Comments
  • © 2026 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(200) PDF downloads(25) Cited by(0)

Article outline

Figures and Tables

Figures(9)  /  Tables(3)

Other Articles By Authors

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog