No evidence for cross resistance between nevirapine and d4T
Simon Collins, HIV i-Base
Two articles published last year (Blanca et al JBC 2003, Baldanti et al AIDS 2003) reported that resistance to d4T (stavudine) was related to the nevirapine-associated Y181C mutation. This included a report that Y181C/I should eight fold resistance to d4T in a recombinant virus assay.
Prompted by the important implications of such cross-resistance on current interpretation systems for resistance reports Klaus Korn from the University of Erlangen-Nuremberg looked for corroborative evidence from a database of 500 RT genotype samples and corresponding phenotypic data to d4T.
427/511 samples without Y181C showed a median resistance factor for d4T of 1.8 (IQR 1.0-2.9). The 84/511 samples with Y181C had a corresponding resistance factor of 2.7 (IQR 1.3-5.4). However this difference was explained by strong linked to RTI mutations in the same sequences. The 3/84 samples without RTI resistance had resistance factors of 1.0, 1.1 and 1.4. Similarly only 16/59 samples with phenotypic resistance to d4T > 8-fold had Y181C.
The study therefore failed to find an association between Y181C and d4T sensitivity and concluded that d4T should not be avoided as a treatment option on the basis of this genotypic mutation.
Korn K, Schmidt B, Walter H. No evidence for stavudine resistance due to nevirapine-selected mutation Y181C in HIV-1 reverse transcriptase in a large genotype/phenotype database. XIII Intl HIV Drug Resistance Workshop, 2004. Abstract 43. Antiviral Therapy 2004; 9:S49.