Abstract
Despite the fact that over 90% of HIV-1 infected people worldwide harbor non-subtype B variants of HIV-1, knowledge of resistance mutations in non-B HIV-1 and their clinical relevance is limited. Due to historical delays in access to antiretroviral therapy (ART) on a worldwide basis, the vast majority of reports on drug resistance deal with subtype B infections in developed countries. However, both enzymatic and virological data support the concept that naturally occurring polymorphisms among different nonB subtypes can affect HIV-1 susceptibility to antiretroviral drugs (ARVs), the magnitude of resistance conferred by major mutations, and the propensity to acquire some resistance mutations. Tools need to be optimized to assure accurate measurements of drug susceptibility of non-B subtypes. Furthermore, there is a need 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 selection of second-line regimens. It will be essential to pay attention to newer drug combinations in well designed long-term longitudinal studies involving patients infected by viruses of different subtypes.
Highlights
Most HIV infections worldwide are due to non-subtype B infections [1]
Because differences in codon sequences at positions associated with drug resistance mutations might predispose viral isolates from different subtypes to encode different amino acid substitutions, it is possible that HIV-1 genetic diversity may influence the type of resistance mutations that might eventually emerge upon drug exposure as well as the rate of emergence of resistance [8,9]
In Botswana, subtype C patients treated with ZDV/ddI developed an atypical thymidine analogue resistance pathway (67N/70R/215Y) compared to subtype B [23], that was not observed in patients with subtype C in India, South Africa, or Malawi [24,25,26,27]
Summary
Most HIV infections worldwide are due to non-subtype B infections [1]. HIV-1 group M has been classified into subtypes, circulating and unique recombinant forms (CRF and URF, respectively) because of its significant natural genetic variation. There is a potential for genetic differences among subtypes to yield differential patterns of resistance-conferring mutations in response to ARV pressure This possibility is supported by the fact that HIV-1 naturally varies in genetic content by as much as 35% among subtypes. Because differences in codon sequences at positions associated with drug resistance mutations might predispose viral isolates from different subtypes to encode different amino acid substitutions, it is possible that HIV-1 genetic diversity may influence the type of resistance mutations that might eventually emerge upon drug exposure as well as the rate of emergence of resistance [8,9] This diversity may affect the degree of cross-resistance to ARVs of the same class, with the potential to impact on clinical outcomes, preservation of immunological responsiveness, and virologic failure [8]. Resistance tests may often be performed only on participants enrolled in study cohorts or trials but not in general practice
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