Human immunodeficiency virus type 1 protease cleavage site mutations associated with protease inhibitor cross-resistance selected by indinavir, ritonavir, and/or saquinavir

We examined the prevalence of cleavage site mutations, both within and outs ide the gag region, in 28 protease inhibitor (PI) cross-resistant patients treated with indinavir, ritonavir, and/or saquinavir compared to control pa tients treated with reverse transcriptase inhibitors. Three human immunodef iciency virus protease cleavage sites within gag (p2/NC, NC/p1, and NC/TFP) showed considerable in vivo evolution before and after therapy with indina vir, ritonavir, and/or saquinavir. Another gag cleavage site (p1/p6(gag)) s howed a trend compared to matched controls. The other eight recognized clea vage sites showed relatively little difference between PI-resistant cases a nd controls. An A-->V substitution at the P2 position of the NC/p1 and NC/T FP cleavage sites was the most common (29%) change selected by the PIs used in this study.