Emergence of the H208Y mutation in the reverse transcriptase (RT) of HIV-1 in association with nucleoside RT inhibitor therapy

Objectives: The aim of the study was to determine whether mutations at RT codon 208 are associated with nucleoside RT inhibitor (NRTI) exposure, NRTI resistance patterns and HIV-1 subtype. Methods: Six thousand three hundred and fifty two genotypic resistance tests linked to a clinical database were analysed. Results: The prevalence of mutations at codon 208 was 6/2347 (0.3%) in treatment-naive and 165/4005 (4.1%) in treatment-experienced persons. H208Y was the most common mutation in both groups (0.2% and 3.8%, respectively) and occurred in 4.5% of treatment-experienced persons with Subtype B, 1.7% of those with Subtype C and 0.7% of those with other non-B subtypes (P = 0.001). The association with subtypes was independent of treatment experience. H208Y showed a strong association with NRTI experience, which persisted after adjusting for subtype [odds ratio (OR) 19.34; 95% confidence interval (CI) 7.87-47.54; P = 0.0001]. The prevalence of H208Y was highest in genotypes harbouring M184V and the thymidine analogue mutations (TAMs) M41L, D67N, L210W and T215Y. The median number of TAMs was 4 and 0 in genotypes with and without H208Y, respectively (P = 0.0001). The prevalence of H208Y declined over time, being highest in 1998 (9.9%) and lowest in 2003 (0.9%) (P = 0.0001). Conclusions: There is a strong association between H208Y and NRTI experience, particularly in persons with Subtype B harbouring multiple NRTI resistance mutations. These findings indicate an accessory role for H208Y in NRTI resistance