No evidence for cross resistance between nevirapine and d4T

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.