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JAC Advance Access originally published online on September 10, 2008
Journal of Antimicrobial Chemotherapy 2008 62(6):1188-1190; doi:10.1093/jac/dkn374
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© The Author 2008. 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

Original research

Detection of low-frequency K103N mutants after unstructured discontinuation of efavirenz in the presence of the CYP2B6 516 TT polymorphism

Ana Garcia-Diaz1, Chun Blok1, Sara Madge1, Clare Booth1, Mervyn Tyrer1, Stefano Bonora2, Tabitha Mahungu1, Andrew Owen3, Margaret Johnson1 and Anna Maria Geretti1,*

1 Royal Free Hospital and Royal Free and University College Medical School, London, UK 2 Department of Infectious Diseases, University of Turin, Italy 3 Department of Pharmacology, University of Liverpool, Liverpool, UK

Received 24 May 2008; returned 30 June 2008; revised 4 August 2008; accepted 11 August 2008

* Correspondence address. Department of Virology, Royal Free Hospital, Pond Street, London NW3 2QG, UK. Tel: +44-20-7794-0500 ext. 36295; Fax: +44-20-7830-2854; E-mail: a.geretti{at}medsch.ucl.ac.uk

Objectives: To measure antiretroviral drug plasma levels in newly diagnosed HIV-1 seropositive persons who presented with an undetectable plasma HIV-1 RNA load but gave no history of antiretroviral drug exposure and to determine the impact of interrupting undisclosed or unknown antiretroviral therapy on the emergence of drug resistance.

Patients and methods: Five newly diagnosed, reportedly drug-naive HIV-1 seropositive persons were included in the study. Drug resistance was determined by population and clonal sequencing of reverse transcriptase and protease. CYP2B6 polymorphisms were assayed by real-time PCR allelic discrimination on pre-amplified exons.

Results: Efavirenz was detected in the plasma of one of the five persons coinciding with a viral load <40 copies/mL by two different assays. When efavirenz became undetectable, the viral load rebounded. The patient was CYP2B6-516T homozygous. Population sequencing showed wild-type subtype D virus, whereas clonal sequencing detected low-frequency (2%) K103N. The patient firmly denied antiretroviral exposure but described the use of Ugandan remedies.

Conclusions: In migrating populations seeking HIV testing, careful and compassionate counselling is required to facilitate the disclosure of previous diagnosis and therapy. The use of remedies of dubious content should also be discussed and investigated.

Keywords: remedies , low-frequency resistant mutants , efavirenz clearance


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