COMPETITION BETWEEN ZIDOVUDINE-SENSITIVE AND ZIDOVUDINE-RESISTANT STRAINS OF HIV

Objective: To investigate competitive interactions between zidovudine-sensitive and resistant strains of HIV within the context of host-parasite population dynamic interactions between CD4+ cells and HIV. Design: A mathematical model of the population dynamics of CD4+ cells, sensitive HIV and resistant HIV is developed. Methods: The model is analysed numerically and analytically and model predictions are compared with previously published data on population dynamics of HIV and CD4+ cells in patients receiving zidovudine. A threshold result describing the critical dose of zidovudine above which resistant HIV will out-compete sensitive HIV is derived, as are expressions describing the critical effective doses for the eradication of sensitive and resistant strains. Numerical simulations of the dynamics of the shift from the pre-treatment, equilibrium to the treatment equilibrium are presented and an analytic expression approximating the time taken until virus growth restarts is derived. Results: It is shown that competition between strains of virus is the important factor determining which type of virus will eventually start to grow during the course of zidovudine treatment, but host-parasite interactions are the important determinant of when viral resurgence occurs. Conclusions: Although resistant strains are observed after prolonged treatment with zidovudine, this model suggests that it is the growing supply of uninfected CD4+ cells which causes the eventual upsurge in viral burden.