Underestimation of HIV type 1 drug resistance mutations: results from the ENVA-2 genotyping proficiency program

Current recommendations indicate the use of HIV-1 drug resistance genotyping in the treatment of HIV-1 infection, primarily on treatment failure, and in specific instances also before the initiation of therapy. As such, HIV-1 genotyping is becoming a standard of care parameter in HIV-1 treatment monitoring and a rapidly increasing number of laboratories now use this technology routinely. A study of proficiency, using the ENVA-2 panel, was performed to evaluate the current HIV-1 resistance genotyping quality in 34 laboratories from different parts of the world. The results demonstrated extensive interlaboratory variation in the quality of genotyping and a significant underestimation of resistance mutations, even in samples expressing pure mutant genotype. The level of variation could not be attributed to the sequencing technology used and was therefore considered to be laboratory associated. The direct clinical consequences of this may be inadequate treatment of HIV-1-infected individuals and a more rapid exhaustion of therapeutic options for the patients. Drug resistance mutations are frequently missed. Therefore, quality control programs are urgently needed. Until these are widely implemented, clinicians must consider this issue and interpret the reported genotyping results with caution.