Background:  Approximately 40% of adults in Botswana are HIV-infected. The Botswana ART program began in 2002 and currently treats 34,000 patients with a goal of treating 85,000 patients (~30% of HIV-infected adults) by 2009. We predict the stochastic evolution of drug-resistant strains of HIV that may emerge as a consequence of this treatment program. Specifically, we predict the magnitude and temporal dynamics of the evolution of transmitted drug-resistant strains. We discuss the implications of our results in the context of the World Health Organization’s (WHO’s) proposed surveillance system for detecting drug-resistant strains of HIV in Africa.

Methods:  We present a novel stochastic dynamic model of the emergence and evolutionary dynamics of drug resistance. We use our model to formulate a birth-death-immigration master equation, and use this equation to obtain an analytical solution of probabilistic evolutionary trajectories. We incorporate demographic and treatment data into our model to make specific predictions for Botswana.

Results:  Our stochastic evolutionary trajectories show that, even if rates of acquired resistance are high, but the drug-resistant strains that evolve are only half as fit (i.e., transmissible) as wild type strains, then transmission of these drug-resistant strains would remain low (<5% by 2009) and would likely be undetectable by the WHO’s surveillance system. However, our stochastic evolutionary trajectories show that transmission of drug-resistant strains in Botswana could increase to ~15% by 2009 if the resistant strains are as fit as wild type strains.

Conclusions:  The WHO’s surveillance system is designed to detect transmitted resistance that exceed a threshold level of 5%. Whether this system will detect drug-resistant strains in Botswana by 2009 will depend upon the fitness of the strains that evolve. Our results imply that it will be many years before the WHO will detect transmitted resistance in other sub-Saharan African countries with less ambitious treatment programs than Botswana.