Extensive polymorphisms observed in HIV–1 clade B protease gene using high–density oligonucleotide arrays

Naturally occurring mutations in HIV–1–infected patients have important implications for therapy and the outcome of clinical studies. However, little is known about the prevalence of mutations that confer resistance to HIV–1 protease inhibitors in isolates derived from patients naive for such inhibitors. In the first clinical application of high–density oligonucleotide arraysequencing, the sequences of 167 viral isolates from 102 patients have been determined. The DNA sequence of USA HIV–1 clade B proteases was found to be extremely variable and 47.% of the 99 amino acid positions varied. This level of amino acid diversity is greater than that previously known for all worldwide HIV–1 clades combined (40%). Many of the amino acid changes that are known to contribute to drug resistance occurred as natural polymorphisms in isolates from patients who had never received protease inhibitors.