The vast majority of reports on drug resistance deal with subtype B infections in developed countries, and this is largely due to historical delays in access to antiretroviral therapy (ART) on a worldwide basis. This notwithstanding the concept that naturally occurring polymorphisms among different non-B subtypes can affect HIV-1 susceptibility to antiretroviral drugs (ARVs) is supported by both enzymatic and virological data. These findings suggest that such polymorphisms can affect both the magnitude of resistance conferred by some major mutations as well as the propensity to acquire certain resistance mutations, even though such differences are sometimes difficult to demonstrate in phenotypic assays. It is mandatory that tools are optimized to assure accurate measurements of drug susceptibility in non-B subtypes and to recognize that each subtype may have a distinct resistance profile and that differences in resistance pathways may also impact on cross-resistance and the choice of regimens to be used in second-line therapy. Although responsiveness to first-line therapy should not theoretically be affected by considerations of viral subtype and drug resistance, well-designed long-term longitudinal studies involving patients infected by viruses of different subtypes should be carried out. 1. Introduction Nonsubtype B infections are responsible for most HIV cases worldwide [1]. HIV-1 group M has been classified into subtypes, circulating and unique recombinant forms (CRF and URF, resp.), due to its significant natural genetic variation; this includes subtypes A–D, F–H, and J–K and many CRFs and URFs. Although subtype B is the most prevalent in the Western World (Western Europe, the Americas, Japan, and Australia), non-B subtypes predominate in the rest of the world: that is, subtype C in sub-Saharan Africa, India, and Brazil, CRF01_AE in South East Asia, CRF02_AG in West Africa, and subtype A in Eastern Europe and Northern Asia [1–3]. The proportion of non-B subtypes in North and South America and Western Europe is increasing [4–7]. Combination antiretroviral therapy (ART) is now used in many areas of the world, and HIV resistance to antiretroviral drugs (ARVs) has widely emerged. Thus, non-B subtypes will presumably become even more common in western countries. Reduced sensitivity to ARVs in non-B subtypes has been less well studied than in subtype B, mainly because of the predominance of subtype B in those countries in which ARVs first became available, coupled with the availability of genotypic and phenotypic antiretroviral drug resistance testing in
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