Frequency of multinucleoside analogue-resistant genotypes observed during antiretroviral therapy

A mutation at codon 151 (151M) and insertions at codon 69 of HIV-1 reverse transcriptase (RT) (69S) have been noted to confer over fourfold phenotypic resistance to all currently approved nucleoside analogue antiretroviral agents. The occurrence of the 151M and 69S mutations therefore substantially limits treatment options for second line or salvage therapy. If resistance testing is not routinely used in clinical practice, and these mutations are not detected before initiating a new regimen, potentially useful agents or classes may be wasted by inclusion in a sub-optimal treatment regimen. Previous data have suggested that zidovudine (ZDV)-associated mutations are infrequently observed with the 151M mutation, and that viral fitness may be impacted by these mutations. In mid-1998, we established a resistance testing programme at the Chelsea and Westminster Hospital in London, UK, using Vircogen sequencing to evaluate resistance mutations in individuals experiencing viral rebound on the first and subsequent antiretroviral treatment regimens. The presence of the 151M and 69S mutations was tabulated with treatment history, CD4 cell count and viral load at testing to establish factors associated with the detection of this mutation. In addition, details of other mutations in RT were tabulated.