INTRODUCTION: The FEM-PrEP trial was a pre-exposure prophylaxis clinical trial 
to test the safety and efficacy of Truvada (tenofovir disoproxil fumarate and 
emtricitabine) in the prevention of human immunodeficiency virus infection. 
Because Truvada can suppress hepatitis B virus replication, and withdrawal of 
Truvada can cause hepatic flares in patients with chronic hepatitis B, 
pre-enrollment screening included serological screening for hepatitis B virus 
markers. Women with chronic infections were not enrolled in the trial. Women 
found to be unprotected against hepatitis B were enrolled and offered three 
doses of hepatitis B vaccine. Reinfection and reactivation of previously 
resolved hepatitis B virus infections have been documented in immunosuppressed 
individuals but not in healthy individuals. We present the case of a participant 
enrolled in the FEM-PrEP clinical trial with baseline evidence of immunity 
against hepatitis B virus who subsequently developed acute hepatitis B.
CASE PRESENTATION: A 21-year-old Black non-pregnant woman was enrolled in the 
FEM-PrEP trial. She was human immunodeficiency virus-negative and a serological 
test for hepatitis B virus was negative. She had evidence of low levels of 
protection against hepatitis B virus and normal liver function. She had no 
hepatitis B vaccination history, thus it was concluded that she had 
post-infection immunity. At week 36 she presented with severely elevated liver 
enzyme levels that, upon further investigation, were a result of acute hepatitis 
B virus infection. The infection followed an asymptomatic course until full 
recovery of her liver enzymes a few weeks later. At study unblinding, the 
participant was found to be on the Truvada arm. Retrospective plasma drug level 
testing found low levels of study drugs from week 4. The participant remained 
human immunodeficiency virus-negative throughout the study.
CONCLUSION: Hepatitis B virus infection reactivation or reinfection is a rare 
phenomenon in healthy individuals. However, reactivations have been reported in 
patients being treated for chronic hepatitis B with the drugs contained in 
Truvada, after treatment had been withdrawn. This participant may have 
reactivated after stopping Truvada, or she may have reactivated spontaneously 
owing to relatively low levels of protective antibodies against hepatitis B. 
Alternatively, she may have been reinfected. Clinicians should be aware that 
hepatitis B virus reactivation or reinfection may cause elevated transaminases 
even in the presence of low baseline immunity.