High prevalence of primary Enfuvirtide (ENF) resistance-associated mutations in HIV-1-infected patients in Hong Kong.
BACKGROUND
Enfuvirtide (ENF) is a viral fusion inhibitor used in patients failing highly active antiretroviral therapy (HAART). Mutations associated with ENF resistance have been identified within amino acid positions 36-45 of gp41. As ENF will be introduced to Hong Kong, an understanding of the prevalence of naturally occurred ENF resistance mutations is important before implementation of ENF treatment.


OBJECTIVE
To investigate the prevalence of ENF resistance-associated mutations in the HR1 and HR2 of HIV-1 strains obtained from ENF-naïve patients.


METHODS
HIV-1 strains isolated from 185 patients (156 antiretroviral treatment [ART]-naïve and 29 HAART-experienced) were screened for ENF resistance-associated mutations using RT-PCR and DNA sequencing.


RESULTS
Primary mutations were detected in 19.4% of HARRT-experienced patients and 20.5% of ART-naïve patients. G36D was encountered most frequently and more prevalent in non-B subtypes. N42S, L54M and V69I were the major polymorphisms detected. N42S and L54M were predominant in CRF01_AE and subtype B, respectively. V69I was found in all samples harboring G36D. In three longitudinal samples from an ENF-treated patient, G36D was detected after ENF treatment for 6 months and the mutation persisted after termination of ENF for 6 months.


CONCLUSIONS
The high prevalence of ENF resistance-associated mutations in HARRT-experienced and ART-naïve patients identified in this study highlights the importance of mutation screening before ENF therapy in Hong Kong. Our findings from the ENF-treated patient showed that G36D mutation persisted as long as 6 months after ENF withdrawal. Phenotypic assays will be necessary to confirm the influence of this mutation to ENF susceptibility.
Leung
P H M
PH
Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.
Chen
J H K
JH
Wong
K H
KH
Chan
K C
KC
Lam
H Y
HY
Cheng
V C C
VC
Yuen
K Y
KY
Yam
W C
WC
D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000494:pharmacology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006723:Hong Kong; D006801:Humans; D020125:Mutation, Missense; D010446:Peptide Fragments / Q000494:pharmacology*; D015995:Prevalence; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D012367:RNA, Viral; C514787:gp41 protein, Human immunodeficiency virus 1; D000077560:Enfuvirtide