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

Abstract

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. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.