Multidrug-Resistant Variants of HIV Type 1 (HIV-1) Can Exist in Cells as Defective Quasispecies and Be Rescued by Superinfection with Other Defective HIV-1 Variants

A tissue culture cell line infected with multidrug-resistant (MDR) human immunodeficiency virus type 1 (HIV-1) produced only noninfectious particles because of a lethal mutation in env. The defective MDR provirus was rescued by superinfection with either wild-type HIV-1 or a second replication-defective virus lethally mutated in capsid. Drug-resistance phenotyping revealed that the MDR viruses dominated if even single reverse-transcriptase inhibitors were present, reflecting linkage of the various drug resistance mutations on a single viral nucleic acid backbone. These results are most likely attributable to recombination during second rounds of infection and suggest that defective HIV-1 variants may nonetheless constitute part of the HIV-1 reservoir.