Antiretroviral resistance in different HIV-1 subtypes: impact on therapy outcomes and resistance testing...

This review summarizes our knowledge of HIV-1 subtype-related differences associated with antiretroviral drug resistance and its interpretation, and with clinical, immunological and virological therapy outcomes. It also addresses the problem that subtypes are only a crude classification of the genetic diversity relevant to these topics.

Subtype-related variability is responsible for differences in drug resistance. Baseline drug susceptibility and resistance pathways vary between subtypes; such variation is mainly related to differences in the prevalence of specific polymorphisms. The clinical impact of these findings is rather limited, but with the increasing genetic diversity of HIV-1, they have the potential to impact the accuracy of the 'algorithm' concept for genotypic drug resistance test interpretation negatively.

Severe limitations exist in the data describing the association of HIV-1 subtypes with resistance and treatment outcomes, because most data are the result of retrospective observational studies. Even with these limitations, the knowledge gathered allows us to assume that differences in the short-term response to treatment in different subtypes should not greatly affect treatment strategies. As for the interpretation of genotypic resistance testing, new tools are needed, taking into account the entire genomic context and thus overcoming the problem of genetic diversity.