We have previously reported on a sexually active promiscuous MSM receiving tenofovir disoproxil (TDF; 245 mg) as treatment against chronic hepatitis B infection . Although we appreciate the comment by Fox et al. , we would like to highlight a few additional points for consideration. First, TDF therapy has been shown to be highly effective at inducing rapid and sustained suppression of hepatitis B virus (HBV) viral loads. The published case report by Fox et al.  suggests that even at lower levels, TDF is still able to suppress HBV viral loads below the limit of detection, which may be insufficient to prevent HIV infection. In addition, although national and international preexposure prophylaxis (PrEP) guidelines suggest the use of TDF in combination with Emtricitabine (FTC), regular measurements of drug levels are neither recommended for HIV PrEP nor during chronic HBV therapy. Therefore, in most cases, reasons for PrEP failure cannot be fully investigated. In our case report, we had the unique opportunity to track the relative intake frequency of TDF using HBV viral loads as a surrogate marker. Although we pointed out the obvious lack of FTC as an additional barrier for HIV acquisition, the case nevertheless highlights the possibility of PrEP failure in spite of adherent behavior. Indeed, the prevalence of the K65R mutation in German cohorts has been reported to be ∼0.2–2.7% , indicating an individual has a probability to become infected with HIV after exposure even under optimal PrEP adherence. Although this probability is very low, we believe that individuals on PrEP should be aware of this rare but possible outcome. Furthermore, though we cannot exclude the possibility, a recent development of the K65R mutation in our individual is very unlikely. First, given that only 1–2 founder viruses are transmitted during sexual transmission, those viruses required a considerable amount of time in the absence of any TDF levels to seed, replicate and develop escape mutations. The absence of TDF would likely be noticeable in the HBV viral load levels. Second, in the unlikely event that HIV infection had been acquired soon after the last negative HIV test, a period of 3 months with viral loads around the limit of detection is a rather short amount of time to develop a K65R mutation. Taken together, although we know a protective barrier against HIV falls when a condom breaks, there are not any visible warning signs in the case of PrEP. However, we agree that PrEP is an important part of the prevention package and should be promoted.
Conflicts of interest
There are no conflicts of interest.
1. Streeck H, Verheyen J, Storim J, Dittmer U, Jochum C, Timm J, Esser S. Preexposure prophylaxis failure with tenofovir disoproxil
2. Fox J, Collins S. HIV prevention: response to pre-exposure prophylaxis failure with tenofovir disoproxil
3. Fox J, Brady M, Alexander H, Davies O, Robinson N, Pace M, et al. Tenofovir disoproxil fumarate fails to prevent HIV acquisition or the establishment of a viral reservoir: two case reports
. Infect Dis Ther
4. Metzner KJ, Rauch P, Braun P, Knechten H, Ehret R, Korn K, et al. Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naive patients
. J Clin Virol