Development of Drug Resistance Mutations in Patients on Highly Active Antiretroviral Therapy: Does Competitive Advantage Drive Evolution

Most physicians that treat individuals with HIV-1 disease are able to successfully suppress viral replicationwith the pharmacologic armamentarium available today. For the majority of patients this resultsin immune reconstitution and improved quality of life. However, a large fraction of these patients havetransient elevations in their viral burden and even persistence of low-level viremia. In fact, many individualswhose viral load is suppressed to < 50 c/ml have evidence of low-level viral replication.The impact of low-level viremia and persistent viral replication is an area of significant study and interestowing to the potential for the development of drug resistance mutations. Here the fundamental questionis whether and perhaps what factors provide a venue for the development of resistant virus. Theconcern is clearly the eventual progression of disease with the exhaustion of treatment options.The purpose of this review is to evaluate the current literature regarding the effect of low-level viremiaon the development of drug resistance mutations. Herein, we discuss the impact of differentlevels of viral suppression on the development of mutations. In addition, we look at the role thatresistance and fitness play in determining the survival of a breakthrough mutation within the backgroundof drug.