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


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.
Garcia-Diaz
Ana
A
Royal Free Hospital and Royal Free and University College Medical School, London, UK.
Lok
Chun Bong
CB
Blok
Chun
C
Madge
Sara
S
Booth
Clare
C
Tyrer
Mervyn
M
Bonora
Stefano
S
Mahungu
Tabitha
T
Owen
Andrew
A
Johnson
Margaret
M
Geretti
Anna Maria
AM
D000480:Alkynes; D019943:Amino Acid Substitution / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D048588:Benzoxazines / Q000627:therapeutic use*; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D019562:Viral Load
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1; C098320:efavirenz