Evolution of Human Immunodeficiency Virus Type 1 Populations after Resumption of Therapy following Treatment Interruption and Shift in Resistance Genotype

Conventional genotyping of human immunodeficiency virus type 1 often reveals a shift from a drug-resistant genotype to a wild-type genotype after treatment interruption. A real-time polymerase chain reaction-based technique was used to detect minority resistant populations in 13 patients who showed genotype reversion after interruption of treatment for 3 months. Sixty-two percent of patients in whom the V82A and L90M protease mutations were no longer detectable by conventional genotyping still harbored minority resistant variants, in proportions ranging from 0.1% to 21%. None of the patients with these minority resistant variants who received a protease-inhibitor regimen on resumption of therapy had a response to treatment. However, population sequencing and clonal analysis of plasma samples obtained 1-2 months after resumption of treatment revealed the presence of wild-type virus during the initial decline in plasma virus load, which indicates that minority resistant variants were not rapidly selected.