Human immunodeficiency virus type 1 genetic evolution in patients with prolonged suppression of plasma viremia

Treatment of human immunodeficiency Virus type 1 (HIV-1)-infected patients with combination drug regimens results in a reduction of plasma viral load to levels below the limit of detection. To investigate the genomic fluctuat ions In HIV-1 populations from long-term responders to antiviral therapies we analyzed the viral sequence evolution of env and pol genes from sequenti al peripheral blood mononuclear cell (PBMC) DNA samples of three infected p atients. Analyses of sequences covering the vs and flanking env regions obt ained from blood samples at the beginning of the therapy and at 14 or 24 mo nths from baseline revealed that HIV-1 quasispecies continue to evolve in t he three patients following combination antiretroviral therapy. Minor drug- resistant mutant subpopulations were also searched for and found in one pat ient Interestingly, no minor resistant subpopulations were found in the oth er two patients despite the fact that they showed evidence of ongoing viral replication. Finally, the genetic analysis of the env gene shows a reducti on in PBMC env viral population diversity after long-term response to the t herapy in all the patients analyzed. (C) 1999 Academic Press.