Role of Y318F mutation in NNRTI resistance
Simon Collins and Polly Clayden, HIV i-Base
Further information was provided by Kemp and colleagues on the role of the significance of the Y318F RT mutation in NNRTI resistance. 
A search of genotype and phenotype results from the Virco database investigated this association and site-directed mutant viruses harbouring single or multiple NNRTI-associated mutations were constructed to determine phenotypic susceptibility.
The presence of 318F predicted a >10-fold increase in resistance, irrespective of other mutations in 83% isolates to efavirenz, 95% of isolates to nevirapine and 99% of isolates to delavirdine. The prevalence of 318 within the database was found to be 5% amongst those with K103N , 2% with Y181C and 15% with the delavirdine associated P236L mutation.
318 alone in site-directed mutant virus only produced a <3 fold increase in resistance to nevirapine or efavirenz (and 41-fold increase to delavirdine). In combination with either 103N, 181C or both this produced increases in resistance to efavirenz of 15-42-fold, 1.2-3.3-fold and 23-84-fold respectively.
It may therefore be important to include this outer region of RT in genotypic assays when assessing NNRTI resistance.
- Kemp, SD et al – A mutation in HIV-1 reverse transcriptase at codon 318 (Y-F) confers high level NNRTI resistance in clinical samples. Antiviral Therapy 2001; 6 (Supplement1):36. Abstract 44.