Title:The WHO surveillance threshold and the emergence of drug-resistant HIV strains in Botswana

Abstract: Background: Approximately 40% of adults in Botswana are HIV-infected. The Botswana antiretroviral 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 evolution of drug-resistant strains of HIV that may emerge as a consequence of this treatment program. We discuss the implications of our results for the World Health Organization's (WHO's) proposed surveillance system for detecting drug-resistant strains of HIV in Africa. Methods: We use a mathematical model of the emergence of drug resistance. We incorporate demographic and treatment data to make specific predictions as to when the WHO surveillance threshold is likely to be exceeded. Results: Our results show - even if rates of acquired resistance are high, but the drug-resistant strains that evolve are only half as transmissible as wild-type strains - that transmission of drug-resistant strains will remain low (< 5% by 2009) and are unlikely to exceed the WHO's surveillance threshold. However,our results show that transmission of drug-resistant strains in Botswana could increase to ~15% by 2009 if resistant strains are as transmissible as wild-type strains. Conclusion: The WHO's surveillance system is designed to detect transmitted resistance that exceeds a threshold level of 5%. Whether this system will detect drug-resistant strains in Botswana by 2009 will depend upon the transmissibility of the strains that emerge. Our results imply that it could be many years before the WHO detects transmitted resistance in other sub-Saharan African countries with less ambitious treatment programs than Botswana.