Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV‐1 subtypes: implications for pre‐exposure prophylaxis

Introduction Tenofovir‐containing regimens have demonstrated potential efficacy as pre‐exposure prophylaxis (PrEP) in preventing HIV‐1 infection. Transmitted drug resistance mutations associated with tenofovir, specifically the reverse transcriptase (RT) mutation K65R, may impact the effectiveness of PrEP. The worldwide prevalence of transmitted tenofovir resistance in different HIV‐1 subtypes is unknown. Methods Sequences from treatment‐naïve studies and databases were aggregated and analyzed by Stanford Database tools and as per the International AIDS Society (IAS‐USA) resistance criteria. RT sequences were collected from GenBank, the Stanford HIV Sequence Database and the Los Alamos HIV Sequence Database. Sequences underwent rigorous quality control measures. Tenofovir‐associated resistance mutations included K65R, K70E, T69‐insertion and ≥3 thymidine analogue mutations (TAMs), inclusive of M41L or L210W. Results A total of 19,823 sequences were evaluated across diverse HIV‐1 subtypes (Subtype A: 1549 sequences, B: 9783, C: 3198, D: 483, F: 372, G: 594, H: 41, J: 69, K: 239, CRF01_AE: 1797 and CRF02_AG: 1698). Overall, tenofovir resistance prevalence was 0.4% (n=77/19,823, 95% confidence interval or CI: 0.3 to 0.5). K65R was found in 20 sequences (0.1%, 95% CI: 0.06 to 0.15). Differences in the prevalence of K65R between HIV‐1 subtypes were not statistically significant. K70E and ≥3 TAMs were found in 0.015% (95% CI: 0.004 to 0.04) and 0.27% (95% CI: 0.2 to 0.4) of sequences, respectively. Conclusions Prevalence of transmitted K65R and other tenofovir resistance mutations across diverse HIV‐1 subtypes and recombinants is low, suggesting minimal effect on tenofovir‐containing PrEP regimens.