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.