Resistance and viral subtypes: how important are the differences and why do they occur?

Purpose of reviewThe global HIV-1 pandemic has evolved to include 11 subtypes and 34 circulating recombinant forms. Our knowledge of HIV-1 response to antiretroviral drugs and emergent drug resistance has, however, been limited to subtype B infections circulating in Europe and North America, with little comparative information on non-B subtypes representing approximately 90% of worldwide epidemics. This review summarizes publications in the past year that highlight intersubtype differences influencing viral susceptibility to antiretroviral drugs and emergent drug resistance. Recent findingsCumulative findings from clinical studies suggest that antiretroviral therapy will be of benefit in the overall treatment of non-B subtype infections, and result in drug-resistance profiles comparable to those observed for subtype B infections. Nevertheless, the 10–15% sequence diversity in the Pol region contributes to intersubtype differences in response to particular nucleoside and non-nucleoside analogues, as well as protease inhibitors. Distinct signature mutations and mutational pathways are identified for specific non-B subtypes. The implications of subtype on clinical outcome and interpretative algorithms are described. SummaryUnderstanding intersubtype differences in drug resistance is important in optimizing treatment strategies in resource-poor settings. Hopefully, this may assist in the design of prophylactic approaches to prevent HIV-1 horizontal and vertical HIV-1 transmission.

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