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JAC Advance Access originally published online on April 19, 2007
Journal of Antimicrobial Chemotherapy 2007 59(6):1047-1056; doi:10.1093/jac/dkm082
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Review

Prevalence and determinants of transmitted antiretroviral drug resistance in HIV-1 infection

Clare L. Booth and Anna Maria Geretti*

Royal Free Hospital and Royal Free and University College Medical School, London, UK

* Correspondence address. Department of Virology, Royal Free Hospital, Pond Street, London NW3 2QG, UK. Tel: +44-20-7794-0500, ext. 6295; Fax: +44-20-7830-2854; E-mail: a.geretti{at}medsch.ucl.ac.uk

Transmission of drug-resistant HIV-1 variants from antiretroviral treatment-experienced persons has been documented to occur through multiple routes, including sexual intercourse, intravenous drug use and vertically from mother to child. Newly infected persons with transmitted drug resistance (TDR) also act as a source for the onward transmission of resistant variants. Rates of virological suppression and behavioural patterns of treated populations and the relative fitness of drug-resistant variants are important determinants of the prevalence of TDR. Current estimates indicate that the prevalence is highest in regions and populations with long-established use of antiretroviral therapy. Limited data suggest that the incidence of TDR is rising in developing countries where access to therapy is increasing. There are methodological variations between studies, however, including those relative to the selection of the study population and the resistance interpretation system, which can skew prevalence estimates. TDR has important implications for the successful management of antiretroviral therapy. Routine resistance testing of drug-naive persons has been widely adopted in affluent countries and shown to effectively guide the selection of first-line regimens. Genotypic resistance tests offer a practical approach for detecting TDR. However, routine methods can only detect resistant mutants within the dominant quasispecies and fail to detect low-frequency resistant variants, which may become important once selective drug pressure is introduced. More sensitive testing methods are being evaluated but remain research tools at present. In addition, factors such as superinfection and possible differences in resistance patterns between plasma and cellular reservoirs and between anatomical compartments should be considered when evaluating TDR.

Keywords: primary resistance , HAART , newly diagnosed


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