HIV type 1 (HIV-1) drug resistance mutations were selected during antiretro
viral therapy successfully suppressing plasma HIV-1 RNA to <50 copies/ml. N
ew resistant mutant subpopulations were identified by clonal sequencing ana
lyses of viruses cultured from blood cells. Drug susceptibility tests showe
d that biological clones of virus with the mutations acquired during succes
sful therapy had increased resistance. Each of the five subjects with new r
esistant mutants had evidence of some residual virus replication during hig
hly active antiretroviral therapy (HAART). based on transient episodes of p
lasma HIV-1 RNA > 50 copies/ml and virus env gene sequence changes. Each ha
d received a suboptimal regimen before starting HAART. Antiretroviral-resis
tant HIV-1 can be selected from residual virus replication during HAART in
the absence of sustained rebound of plasma HIV-1 RNA.