HIV-1 Drug-Resistant Minority Variants: Sweating the Small Stuff

Abstract

Within each human immunodeficiency virus (HIV)–infected individual, there exists a remarkably heterogeneous collection of viruses. Over the course of a typical HIV infection, a starting population of relatively homogeneous virus may undergo substantial diversification, such that mutations may be detected at >10% of nucleotide positions [1]. This diversity is driven both by the error-prone nature of HIV reverse transcription and the high rate of viral replication. The HIV reverse transcriptase enzyme lacks a proofreading mechanism, and it is estimated that up to 5 mutations may be introduced during each replication cycle [2, 3]. In addition, the virus is thought to undergo 10–100 million rounds of replication daily, leading to the production of more than a billion new virions [4, 5].