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. Objectives: To investigate the prevalence of ENF resistance-associated mutations in the HR1 and HR2 of HIV-1 strains obtained from ENF-naïve patients. Study design: 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, L54 M 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.