Patients in

areas in which subtype C is endemic have a high rate of the K65R mutation after receiving drug regimens based on stavudine or didanosine (ddI).26 Recent data Pembrolizumab in vitro suggests that the increased rate of K65R acquisition may be due to the differing subtype C RNA template with an increased tendency of the virus to pause events at codon 65.27 Although the B variant is the most prevalent subtype in Western countries more than 90% of patients with HIV-1 infection worldwide have non-subtype B viruses. It is possible that a higher proportion of non-subtype B virus infection was present in our cohort leading to an increased rate of development of K65R mutation. Previous use of ART regimens containing ddI or ABC has also been shown to lead to an increased rate of K65R at XTC/TDF failure. Although patients with a resistance test showing evidence of either the K65R or M184V mutation were excluded from our study patients were not required to have a resistance test at baseline and therefore it is possible

that we observed resistance from previous regimens. In our study no significant difference was found between choice of cytidine analogue and development of K65R mutation which is in accord with data from de Mendoza et al., who described a statistically significant association between co-prescription of both ddI and ABC with TDF and the development of K65R, but no association between selection of K65R and administration ERK inhibitor order of other NRTIs.25 Development of K65R Meloxicam mutation was significantly associated with lower current CD4 count. Study 903 found a statistically significant association between the presence of low CD4 count at baseline and the development of resistance mutation, with a median baseline HIV RNA viral load and CD4 cell count of 246,000 copies/ml

and 24 cells/μl respectively in the two patients who developed the K65R mutation.24 However, Study 934 failed to demonstrate the emergence of K65R mutation despite a similar proportion of subjects with low baseline CD4 T-cell counts.18 To our knowledge, this is the first data suggesting a role for current rather than baseline CD4 cell count in favouring the development of K65R mutation. Further research is required to determine whether this represents a true association. Ongoing viral replication in patients receiving ART promotes the development of drug resistance mutations.27 As expected, the development of both resistance mutations was significantly associated with detectable HIV-1 viraemia (VL > 50 copies/ml). Detectable viraemia may also be a surrogate marker for non-adherence to treatment. Interestingly, we found that episodes of viraemia (VL > 50 copies/ml) amongst patients of black ethnicity were more likely to lead to the development of M184V mutation. A recent systematic review found race/ethnicity to be a significant predictor of virological failure, but this was not attributable to differing rates of resistant HIV-1 minority variants.