Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy.

Historically, in HIV patients, the K65R mutation and thymidine analogue mutations (TAMs) have been reported to rarely coexist. We retrospectively reviewed genotype data from paired samples in a cohort of HIV-1-infected Nigerian patients failing first-line antiretroviral therapies containing zidovudine (AZT) or tenofovir (TDF). Samples for each patient were taken at initial confirmed virological failure ≥1000 copies/ml (S1) and then at the latest available sample with viral load ≥1000 copies/ml before switch to second line (S2). Among 103 patients failing AZT, 19 (18.4%) had TAM-1s, 29 (28.2%) TAM-2s, and 21 (20.4%) mixed TAMs by S2. In contrast, in the 87 patients failing TDF, drug resistance mutations at S2 included K65R in 56 (64.4%), TAM-1s in 1 (1.1%), and TAM-2s in 25 patients (28.7%). Interestingly, 30.4% of patients with K65R in our study developed TAMs. These were exclusively K219E ± D67N and were not predicted to confer a resistance cost to future AZT-containing regimens.