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

PURPOSE OF REVIEW: The 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 FINDINGS: Cumulative 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. SUMMARY: Understanding 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.