Role of HIV Subtype Diversity in the Development of Resistance to Antiviral Drugs 英文参考文献.docVIP

Viruses 2010, 2, 2493-2508; doi:10.3390/v2112493 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Role of HIV Subtype Diversity in the Development of Resistance to Antiviral Drugs Mark A. Wainberg * and Bluma G. Brenner McGill University AIDS Centre, Jewish General Hospital, 3755 Cote-Ste-Catherine Road, Montreal, Quebec, H3T 1E2, Canada; E-Mail: bluma.brenner@mcgill.ca * Author to whom correspondence should be addressed; E-Mail: mark.wainberg@mcgill.ca; Tel.: +1 514-340-8260, ext. 2860; Fax: +1 514-340-7537. Received: 8 October 2010; in revised form: 26 October 2010 / Accepted: 28 October 2010 / Published: 11 November 2010 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. Keywords: HIV; drug resistance; subtype