Profiling resistance-related mutations in the protease region of the pol gene: single genome sequencing of HIV in plasma and peripheral blood mononuclear cells.

Genotypic resistance is currently assessed through direct sequencing, which cannot detect resistant strains below 20%. We compared the genotypic resistance profile of virions and proviruses using population-based analysis and single genome sequencing of the protease region of the pol gene in samples collected from five individuals in whom indinavir monotherapy resulted in treatment failure. Single genome sequencing showed that not all strains present the same resistance mutations, which can be dispersed across different HIV genomes. The resistance profile found in plasma was very similar to that found in peripheral blood mononuclear cells (PBMCs), confirming the utility of assessing proviral DNA as for a means of determining antiretroviral resistance.