HIV pre-exposure prophylaxis (PrEP) is the use of one or more antiretroviral 
medications (in combination) to prevent HIV infection. The most commonly used 
PrEP medication (Truvada® , Gilead Sciences, Inc.) acts by inhibiting HIV-1 
reverse transcriptase. If someone who is using PrEP unknowingly becomes HIV 
infected (termed 'PrEP breakthrough infection'), there may be suppressed viral 
replication resulting in a virus level undetectable by the most sensitive HIV 
NAT. Failure to seroconvert and seroreversion (loss of previously detectable HIV 
antibodies) have also both been observed with 2nd, 3rd and 4th generation 
screening immunoassays, as well as Western blot assays. If such a person was 
tested in the course of donating blood, the results may therefore be difficult 
to interpret. The index of suspicion for possible PrEP 'interference' should be 
highest in the context of concomitant low-level positive or 'greyzone' 
reactivity on HIV NAT and serological tests, which is an unusual pattern in 
acutely HIV-infected blood donors. Another possibility is detectable HIV RNA 
with negative HIV serology (i.e. a potential 'NAT yield' case) but without 
subsequent HIV seroconversion (or disappearance of HIV RNA). Excluding 
antiretroviral therapy or PrEP use by the donor in such circumstances would be 
important. The current rarity of PrEP breakthrough infection indicates that any 
potential safety risk is likely very small. However, considering the increasing 
use of PrEP we feel it is prudent for those interpreting HIV donor screening 
test results to consider the potential for PrEP interference.